Mesenteric hypoperfusion and inflammation induced by brain death are not affected by inhibition of the autonomic storm in rats

array:24 ["pii" => "S1807593222013758" "issn" => "18075932" "doi" => "10.6061/clinics/2015(06)11" "estado" => "S300" "fechaPublicacion" => "2015-06-01" "aid" => "1375" "copyright" => "CLINICS" "copyrightAnyo" => "2015" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "fla" "cita" => "Clinics. 2015;70:446-52" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:19 [ "pii" => "S180759322201376X" "issn" => "18075932" "doi" => "10.6061/clinics/2015(06)12" "estado" => "S300" "fechaPublicacion" => "2015-06-01" "aid" => "1376" "copyright" => "CLINICS" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "fla" "cita" => "Clinics. 2015;70:453-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "REVIEW" "titulo" => "Risk of congenital anomalies associated with antithyroid treatment during pregnancy: a meta-analysis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "453" "paginaFinal" => "459" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 724 "Ancho" => 792 "Tamanyo" => 46543 ] ] "descripcion" => array:1 [ "en" => "Flow chart of the literature search and article selection." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Xiang Li, Gui-Yang Liu, Jian-Li Ma, Liang Zhou" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Xiang" "apellidos" => "Li" ] 1 => array:2 [ "nombre" => "Gui-Yang" "apellidos" => "Liu" ] 2 => array:2 [ "nombre" => "Jian-Li" "apellidos" => "Ma" ] 3 => array:2 [ "nombre" => "Liang" "apellidos" => "Zhou" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S180759322201376X?idApp=UINPBA00004N" "url" => "/18075932/0000007000000006/v1_202212011416/S180759322201376X/v1_202212011416/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1807593222013746" "issn" => "18075932" "doi" => "10.6061/clinics/2015(06)10" "estado" => "S300" "fechaPublicacion" => "2015-06-01" "aid" => "1374" "copyright" => "CLINICS" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "fla" "cita" => "Clinics. 2015;70:441-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "CLINICAL SCIENCE" "titulo" => "Assessments of the associations of thrombus localization with accompanying disorders, risk factors, D-dimer levels, and the red cell distribution width in pulmonary embolism" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "441" "paginaFinal" => "445" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 650 "Ancho" => 780 "Tamanyo" => 34576 ] ] "descripcion" => array:1 [ "en" => "Receiver operating characteristic curve of red blood cell distribution width for predicting the presence of main pulmonary arteries thrombus in studied patients." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Aysel Sunnetcioglu, Bunyamin Sertogullarindan, Bulent Ozbay, Selvi Asker, Salemi Ekin" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Aysel" "apellidos" => "Sunnetcioglu" ] 1 => array:2 [ "nombre" => "Bunyamin" "apellidos" => "Sertogullarindan" ] 2 => array:2 [ "nombre" => "Bulent" "apellidos" => "Ozbay" ] 3 => array:2 [ "nombre" => "Selvi" "apellidos" => "Asker" ] 4 => array:2 [ "nombre" => "Salemi" "apellidos" => "Ekin" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222013746?idApp=UINPBA00004N" "url" => "/18075932/0000007000000006/v1_202212011416/S1807593222013746/v1_202212011416/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "BASIC RESEARCH" "titulo" => "Mesenteric hypoperfusion and inflammation induced by brain death are not affected by inhibition of the autonomic storm in rats" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "446" "paginaFinal" => "452" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Rafael Simas, Sueli G Ferreira, Laura Menegat, Fernando L Zanoni, Cristiano J Correia, Isaac A Silva, Paulina Sannomiya, Luiz F P Moreira" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Rafael" "apellidos" => "Simas" ] 1 => array:2 [ "nombre" => "Sueli G" "apellidos" => "Ferreira" ] 2 => array:2 [ "nombre" => "Laura" "apellidos" => "Menegat" ] 3 => array:2 [ "nombre" => "Fernando L" "apellidos" => "Zanoni" ] 4 => array:2 [ "nombre" => "Cristiano J" "apellidos" => "Correia" ] 5 => array:2 [ "nombre" => "Isaac A" "apellidos" => "Silva" ] 6 => array:2 [ "nombre" => "Paulina" "apellidos" => "Sannomiya" ] 7 => array:4 [ "nombre" => "Luiz F P" "apellidos" => "Moreira" "email" => array:1 [ 0 => "luiz.moreira@incor.usp.br" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM-11), São Paulo/SP, Brazil" "identificador" => "aff1" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Luiz F P Moreira Corresponding author:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 640 "Ancho" => 788 "Tamanyo" => 145231 ] ] "descripcion" => array:1 [ "en" => "Intravital microscopy of the rat mesenteric microcirculation. A, The percentages of perfused small vessels (<30 μm) in sham-operated rats (SH), brain-dead non-treated rats (BD), and brain-dead rats under thoracic epidural blockade (BD-TEB) 180 min after the surgical procedures. The data are presented as the means±SEM; p ANOVA=0.002; *p<0.05 vs. the other groups. B, C, and D, Photomicrographs of mesenteric microvessels in the SH, BD, and BD-TEB groups, respectively." ] ] ] "textoCompleto" => "INTRODUCTIONOrgan transplantation is a unique treatment alternative for many critically ill patients, and one major source of organs is brain-dead patients. Brain death (BD) induces a series of hemodynamic, hormonal, and inflammatory alterations that can deteriorate the viability of organs <a class="elsevierStyleCrossRef" href="#bib1">1</a>–<a class="elsevierStyleCrossRef" href="#bib3">3</a>.Parasympathetic activation associated with progressive bradycardia and hypotension is generally observed after the initial trauma that leads to BD. If the injury involves the most distal midbrain, the vagal cardiac motor center is destroyed, and parasympathetic activity is stopped. As a consequence, sympathetic activity is not regulated by the parasympathetic system, resulting in a classical autonomic storm characterized by tachycardia and hypertension. Finally, a profound reduction in sympathetic outflow leads to hemodynamic instability exacerbated by hypovolemia, dysregulation of the peripheral vasculature, and vasodilatation <a class="elsevierStyleCrossRef" href="#bib4">4</a>.In animal models of BD, a balloon catheter placed in the intracranial cavity is inflated to increase the local pressure, leading to an immediate increase in the norepinephrine and epinephrine concentrations, which are associated with tachycardia and hypertension followed by vasoplegia and hypotension <a class="elsevierStyleCrossRef" href="#bib5">5</a>–<a class="elsevierStyleCrossRef" href="#bib7">7</a>. The prompt appearance of a hypertensive peak followed by an immediate decrease in arterial blood pressure below the baseline level has been observed in models of rapidly increasing intracranial pressure <a class="elsevierStyleCrossRef" href="#bib8">8</a>,<a class="elsevierStyleCrossRef" href="#bib9">9</a>. Alternatively, models of slowly increasing intracranial pressure show a gradual elevation of mean arterial pressure, which is also followed by a hypotensive episode <a class="elsevierStyleCrossRef" href="#bib10">10</a>.Controversial effects documented using different methods of autonomic storm inhibition hamper the understanding of the influence of sympathetic activity on transplantable organs. Administering intravenous propranolol, xylazine, and labetalol <a class="elsevierStyleCrossRef" href="#bib11">11</a>–<a class="elsevierStyleCrossRef" href="#bib13">13</a> inhibits the sudden increase in mean arterial pressure after BD induction, resulting in decreased damage to the myocardial tissue and reduced production of multiple myocardial gene products. In contrast, in a surgical model of sympathectomy in baboons, Novitzky et al. <a class="elsevierStyleCrossRef" href="#bib14">14</a> found that this procedure did not abolish the hypertensive crisis, indicating that the performance of this surgical procedure is not sufficient to block the autonomic storm. In addition, Silva et al. <a class="elsevierStyleCrossRef" href="#bib9">9</a> demonstrated that thoracic epidural anesthesia effectively blocks the autonomic storm but does not alter the expression of inflammatory mediators in the myocardial tissue.The hemodynamic instability observed in BD is generally associated with ischemia and tissue hypoperfusion, which compromise the viability of the organs that are suitable for transplantation <a class="elsevierStyleCrossRef" href="#bib2">2</a>. Previous studies have shown that BD leads to substantial impairment of microcirculation in the liver and the pancreas <a class="elsevierStyleCrossRef" href="#bib15">15</a>,<a class="elsevierStyleCrossRef" href="#bib16">16</a>. Furthermore, our group observed similar alterations triggered by BD in the rat mesenteric microcirculation <a class="elsevierStyleCrossRef" href="#bib8">8</a>. In particular, mesenteric hypoperfusion immediately occurred after BD induction, and this phenomenon persisted for up to three hours thereafter. This hypoperfusion was associated with elevated expression of endothelial cell adhesion molecules and increased leukocyte migration to the perivascular tissues such as in mesentery, lung, and liver tissue <a class="elsevierStyleCrossRef" href="#bib8">8</a>,<a class="elsevierStyleCrossRef" href="#bib17">17</a>.Despite the clear importance of the microcirculation for optimizing the therapy for circulatory shock of various etiologies, the influence of autonomic storm blockade on microcirculatory changes after BD has not been investigated. Therefore, the present study was conducted to assess the role of the microcirculation in hemodynamic and inflammatory events that occur after BD induction and to investigate the effects of sympathetic system inhibition via thoracic epidural anesthesia. Microcirculatory changes, including perfusion and leukocyte-endothelial interactions, were analyzed via intravital microscopy of the mesentery. Local and systemic inflammatory markers were also evaluated.MATERIAL AND METHODSMale Wistar rats (300±50 g) were used according to experimental protocols approved by the Animal Subject Committee of the Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. The animals were randomly allocated to three groups: sham-operated (SH group, n=12), brain-dead non-treated (BD group, n=12), and brain-dead under thoracic epidural blockade (TEB) (BD-TEB group, n=12). The animals were evaluated 180 min after the conclusion of the surgical procedures.Brain death model and thoracic epidural anesthesiaAll animals were anesthetized in a chamber using isoflurane (5%), intubated, and mechanically ventilated (Harvard Apparatus, Holliston, MA, USA) with 100% FiO2 (tidal volume: 10 mL/kg, 70 breaths/min). Sedation was maintained via continuous inhalation of 2% isoflurane. The carotid artery was cannulated for blood pressure monitoring and blood sampling. The jugular vein was cannulated for continuous infusion of saline solution (2 mL/h) to minimize dehydration. No intravenous drugs were administered.BD induction was performed as previously described <a class="elsevierStyleCrossRef" href="#bib9">9</a>,<a class="elsevierStyleCrossRef" href="#bib17">17</a>. Briefly, a Fogarty 4-French catheter (Baxter Health Care, Deerfield, IL, USA) was placed in the intracranial cavity through a drilled parietal burr hole. The balloon catheter was rapidly inflated with 0.5 mL of saline solution to increase the intracranial pressure until BD was confirmed based on maximal pupil dilatation and the absence of the corneal and respiratory reflexes. Anesthesia with isoflurane was discontinued after BD induction.A 10-French polyethylene catheter was placed in the epidural space through an incision over the T11–L1 vertebrae and was advanced to the T5 level. The BD-TEB group received a bolus infusion of 20 µL of 0.5% bupivacaine 5 min before BD induction, followed by continuous infusion (15 µL/h) for 3 h. The animals in the BD group were administered equivalent volumes of saline solution. No drugs were administered to the rats in the SH group.Blood gas, electrolyte, and lactate measurements and white blood cell countsThe blood gas, electrolyte, and lactate levels were measured in blood samples obtained from the carotid artery at baseline (0 min) and 180 min after the surgical procedures using a gas analyzer (Radiometer ABL 555, Radiometer Medical, Copenhagen, Denmark). White blood cell (WBC) counts were determined in blood samples obtained from the cut tip of the tail vein at the same time points. The total WBC counts were determined using a Neubauer chamber. Differential cell counting was performed on stained films via oil immersion microscopy. A total of 100 cells were counted and classified according to standard morphological criteria.Intravital microscopy of the mesenteric microcirculationIntravital microscopy of the mesenteric microcirculation was performed as previously described <a class="elsevierStyleCrossRef" href="#bib8">8</a>. Briefly, an abdominal midline incision was performed 180 min after BD induction, and the distal ileum and its accompanying mesentery were exposed for in vivo microscopic examination of the microcirculation. The animals were maintained on a specially designed stage warmed with circulating 37°C water. The mesentery was continuously perfused with warm (37°C) Krebs-Henseleit solution saturated with a mixture of gases (95% N2 and 5% CO2). A color camera (AxioCam HSc, Carl Zeiss, München-Hallbergmos, Germany) was connected to a triocular microscope (Axioplan 2, Carl Zeiss), and the microcirculatory variables were analyzed using Axiovision 4.1 imaging software (Carl Zeiss). The vascular density in a 1-mm2 area on the computer screen was assessed using a 10x light microscope objective. The flow, defined as continuous or intermittent/absent, was analyzed in vessels with a diameter <30 µm. Five fields of view were selected for each animal. To evaluate leukocyte-endothelial interactions, three post-capillary venules with diameters ranging from 15 to 25 µm were selected for each animal. The number of rolling leukocytes was calculated as the mean number of WBCs passing a designated line perpendicular to the venular axis per 5 min. The adherent cells (i.e., leukocytes that remained stationary on the venular endothelium for more than 30 s) were counted in a 100 µm segment of the vessel. The number of leukocytes that accumulated in the connective tissue adjacent to the selected post-capillary venule was determined in a standard area of 5,000 µm2. Three fields of view for each microvessel were examined.Evaluation of intercellular adhesion molecule 1 expression via immunohistochemistryThe animals were exsanguinated from the abdominal aorta, and the mesentery was removed, immersed in hexane, and frozen in liquid nitrogen. Serial slices of the mesentery (8 µm) were placed on glass slides coated with organosilane (Sigma Chemical Co., St. Louis, MO, USA). The samples were fixed in acetone, and SuperBlock buffer (Pierce Biotechnology, Rockford, IL, USA) was used to block nonspecific sites. For the immunodetection of intercellular adhesion molecule 1 (ICAM-1) on mesenteric microvessels, tissue sections were incubated overnight at 4°C in a biotin-conjugated anti-rat ICAM-1 (CD54) monoclonal antibody (Seikagaku, Tokyo, Japan) diluted 1:50 in phosphate-buffered saline (PBS) containing 0.3% Tween-20. After washing the slides with PBS, the sections were incubated for 1 h at room temperature in streptavidin-fluorescein (Amersham Pharmacia Biotech, London, UK) diluted 1:200 in PBS. After washing with PBS, the samples were treated with Vectashield mounting medium containing propidium iodide (Vector Laboratories, Burlingame, CA, USA) to preserve their fluorescence. The system used for image acquisition included a DS-Ri1 digital camera (Nikon, Tokyo, Japan) connected to a fluorescence microscope (Nikon) controlled with NIS-Elements-BR software (Nikon). The results are presented as the mean fluorescence intensity.Serum concentrations of cytokines and corticosteroneBlood samples obtained from the abdominal aorta were centrifuged (1,500 g, 25°C), and the serum concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-10, and corticosterone were determined using enzyme-linked immunosorbent assay (ELISA) kits as recommended by the manufacturers (cytokines: R&D Systems, Minneapolis, MN, USA; corticosterone: Cayman Chemical, Ann Arbor, MI, USA).Statistical analysisAll data are presented as the means ± standard error of the mean (SEM). The overall group differences were compared via two-way analysis of variance (ANOVA) using group and time as the factors followed by a post hoc Bonferroni test or via a one-way ANOVA followed by a post hoc Bonferroni test. Adjusted p values for multiple comparisons were calculated, and a p-value of <0.05 was considered to indicate statistical significance. All statistical analyses were performed using Graph-Pad Prism 6.1.RESULTSHemodynamic parametersThe rats in the BD group exhibited a sudden increase in mean arterial pressure over the first minute following catheter inflation. In contrast, the rats treated with TEB did not exhibit this hypertensive episode after BD induction. The mean arterial pressure then decreased below the baseline level in both groups. After 75 min, the mean arterial pressure was restored to normal levels, and no difference in mean arterial pressure was observed between the groups. In the SH rats, the mean arterial pressure did not change over time (<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>). There were no significant differences in the arterial blood gas, electrolyte, or lactate levels between the groups (data not shown).<elsevierMultimedia ident="fig1"></elsevierMultimedia>Mesenteric microcirculation parametersThe average proportion of perfused small vessels in the BD group was 39% compared to 74% in the SH rats. The treatment of BD rats with TEB did not alter mesenteric hypoperfusion (43%), as illustrated in <a class="elsevierStyleCrossRef" href="#fig2">Figure 2</a> and the supplementary videos.<elsevierMultimedia ident="fig2"></elsevierMultimedia><elsevierMultimedia ident="fig4"></elsevierMultimedia><a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a> shows the leukocyte-endothelium interaction data obtained from perfused small vessels. Similar results were observed in both the BD and BD-TEB rats, and the number of rolling leukocytes in these two groups was reduced compared to that in the SH group. A reduction in the number of adherent leukocytes in the BD and BD-TEB groups compared to the SH group was also observed. In contrast, the number of migrating leukocytes in both groups of BD rats was higher than that in the SH group. These results were not accompanied by significant changes in the number of WBCs.<elsevierMultimedia ident="tbl1"></elsevierMultimedia>Expression of mesenteric intercellular adhesion molecule 1 and the serum corticosterone levelsThe expression of ICAM-1 was investigated in the mesentery of rats that were not examined via intravital microscopy (<a class="elsevierStyleCrossRef" href="#fig3">Figure 3</a>). The levels of ICAM-1 expression were similar between the BD and BD-TEB groups and exceeded those in the SH group. The serum levels of corticosterone were reduced in the BD and BD-TEB groups compared to the SH group three hours after BD induction (<a class="elsevierStyleCrossRef" href="#fig3">Figure 3</a>).<elsevierMultimedia ident="fig3"></elsevierMultimedia>Serum cytokine levelsSimilar increases in the serum concentrations of TNF-α, IL-1β, IL-6, and IL-10 were observed in the BD, BD-TEB, and SH groups 180 min after the surgical procedures. The reference values obtained in Naive rats were below the limit of detection of the assay. These results are summarized in <a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>.<elsevierMultimedia ident="tbl2"></elsevierMultimedia>DISCUSSIONIn an attempt to attenuate the hemodynamic alterations triggered by BD, thoracic sympathetic blockade was induced in this study via epidural anesthesia with bupivacaine. We found that TEB effectively abolished the hypertensive event observed after BD induction but did not affect the following hypotensive episode. Furthermore, mesenteric hypoperfusion and inflammation, characterized by increased leukocyte migration and ICAM-1 expression, remained unchanged in the BD animals despite TEB. Moreover, the serum levels of cytokines and corticosterone did not change after the treatment of BD rats with TEB.Hemodynamic instability is a major challenge in the treatment of BD donors because it leads to the impairment of organ perfusion and compromises the viability of these organs for transplantation. Although hypertension may occur during the phase of cerebral herniation, hypotension affects almost all patients after BD <a class="elsevierStyleCrossRef" href="#bib18">18</a>. Indeed, in animal models, the hypotensive event that accompanies BD is initiated by both rapid and slow augmentation of intracranial pressure <a class="elsevierStyleCrossRef" href="#bib10">10</a>,<a class="elsevierStyleCrossRef" href="#bib19">19</a>–<a class="elsevierStyleCrossRef" href="#bib21">21</a>. Nevertheless, the important question of how the modification of sympathetic activity after BD impacts microcirculation behavior and hypoperfusion in different organs remains unanswered.In this study, we observed the hemodynamic, microcirculatory, and inflammatory effects of TEB performed immediately before BD induction in rats that did not receive any drugs for blood pressure maintenance. Thus, our non-treated rats are similar to marginal donors in clinical practice. The chemical sympathectomy produced by TEB using bupivacaine prevented the hypertensive event associated with BD, although a slight increase in mean arterial pressure was observed when the balloon was inflated. Furthermore, we demonstrated for the first time that mesenteric hypoperfusion is not affected by the inhibition of the hypertensive episode. The long episode of hypotension that generally starts immediately after the hypertensive peak was not affected by TEB. This event was associated with rapid and persistent hypoperfusion of the mesenteric microcirculation. Such hypoperfusion was previously demonstrated by our group in the mesentery <a class="elsevierStyleCrossRef" href="#bib8">8</a> and by others in the pancreas and the liver <a class="elsevierStyleCrossRef" href="#bib15">15</a>,<a class="elsevierStyleCrossRef" href="#bib16">16</a>. Additional real-time monitoring of the mesenteric microcirculation during the first 30 min after BD induction confirmed that mesenteric hypoperfusion occurs immediately after BD and concomitantly with the onset of the sustained hypotensive episode (unpublished data). This observation suggests that microcirculatory abnormalities can occur independently of an increase in arterial pressure, suggesting the involvement of other mechanisms triggered by BD in these microcirculatory abnormalities.It has been demonstrated that BD leads to a decrease in organ perfusion and a progressive activation of endothelial cells and leukocytes <a class="elsevierStyleCrossRef" href="#bib8">8</a>,<a class="elsevierStyleCrossRef" href="#bib22">22</a>–<a class="elsevierStyleCrossRef" href="#bib25">25</a>. It is known that BD triggers a series of inflammatory effects, including increased expression of adhesion molecules, leukocyte transmigration to the perivascular tissue in various organs, and increased serum levels of cytokines <a class="elsevierStyleCrossRef" href="#bib2">2</a>,<a class="elsevierStyleCrossRef" href="#bib3">3</a>,<a class="elsevierStyleCrossRef" href="#bib26">26</a>–<a class="elsevierStyleCrossRef" href="#bib28">28</a>. The present data indicate that the inflammation in the mesenteric microcirculation is not affected by TEB. The animals in both BD groups exhibited similar numbers of rolling, adherent, and migrating leukocytes, as well as comparably increased levels of ICAM-1 expression in endothelial cells; these characteristics were associated with a pronounced reduction in the serum corticosterone levels. It is known that BD impairs the endocrine system and decreases the release of hormones such as triiodothyronine, thyroxin, cortisol, and anti-diuretic hormone, suggesting an interruption along the hypothalamic-pituitary-adrenal axis <a class="elsevierStyleCrossRef" href="#bib29">29</a>,<a class="elsevierStyleCrossRef" href="#bib30">30</a>. In this regard, it has been shown that in healthy subjects, endogenous glucocorticoids that are secreted in large amounts at the early stages of an inflammatory reaction regulate the functions of almost all cellular components of the microcirculation <a class="elsevierStyleCrossRef" href="#bib31">31</a>. Indeed, the SH rats exhibited increased levels of corticosterone in association with reduced ICAM-1 expression compared to the BD rats. Furthermore, the serum levels of cytokines were similar between the groups, suggesting that the release of cytokines triggered by BD-associated trauma <a class="elsevierStyleCrossRef" href="#bib8">8</a>,<a class="elsevierStyleCrossRef" href="#bib28">28</a> was not affected by TEB.It has been well documented that abnormalities in microcirculatory perfusion, including decreased vascular density, especially in the small vessels, and a large number of non-perfused and intermittently perfused small vessels, which occur in septic patients, are not affected by the global hemodynamic state or the use of adrenergic agents <a class="elsevierStyleCrossRef" href="#bib32">32</a>,<a class="elsevierStyleCrossRef" href="#bib33">33</a>. The experimental findings are consistent with the clinical evidence that sepsis induces microvascular changes that may play an important role in the development of organ dysfunction <a class="elsevierStyleCrossRef" href="#bib32">32</a>,<a class="elsevierStyleCrossRef" href="#bib34">34</a>,<a class="elsevierStyleCrossRef" href="#bib35">35</a>. These results justify the attempts to revert these alterations. Alternatively, microcirculatory targets are not currently considered for optimizing the therapy after BD. Fluid replacement, the use of vasoactive drugs, and hormone replacement therapy are the strategies used to achieve hemodynamic stability and to maintain organ function in potential BD organ donors <a class="elsevierStyleCrossRef" href="#bib18">18</a>. Although these interventions may influence the microcirculation, management aimed at stabilizing the global hemodynamic state does not always ensure the normalization of tissue perfusion, which is an important objective in shock states of various etiologies.In conclusion, the results of this study indicate that epidural anesthesia with bupivacaine does not affect the sustained hypoperfusion and inflammation in the mesenteric microvessels induced by BD, suggesting that microcirculatory abnormalities can occur independently of changes in mean arterial pressure. These findings clearly demonstrate that therapies aimed at maintaining the microcirculation may effectively compensate for the perfusion abnormalities after BD, thereby potentially improving the quality of donor organs for transplantation.AUTHOR CONTRIBUTIONSSimas R participated in the research design, performance of the research, the data analysis, and the writing of the paper. Ferreira SG, Menegat L, Zanoni FL, and Correia CJ participated in the performance of the research. Silva IA participated in the research design and the writing of the paper. Sannomiya P and Moreira LF participated in the research design, the data analysis, and the writing of the paper." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xpalclavsec1582340" "titulo" => "KEYWORDS" ] 1 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 2 => array:3 [ "identificador" => "cesec20" "titulo" => "MATERIAL AND METHODS" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "cesec30" "titulo" => "Brain death model and thoracic epidural anesthesia" ] 1 => array:2 [ "identificador" => "cesec40" "titulo" => "Blood gas, electrolyte, and lactate measurements and white blood cell counts" ] 2 => array:2 [ "identificador" => "cesec50" "titulo" => "Intravital microscopy of the mesenteric microcirculation" ] 3 => array:2 [ "identificador" => "cesec60" "titulo" => "Evaluation of intercellular adhesion molecule 1 expression via immunohistochemistry" ] 4 => array:2 [ "identificador" => "cesec70" "titulo" => "Serum concentrations of cytokines and corticosterone" ] 5 => array:2 [ "identificador" => "cesec80" "titulo" => "Statistical analysis" ] ] ] 3 => array:3 [ "identificador" => "cesec90" "titulo" => "RESULTS" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "cesec100" "titulo" => "Hemodynamic parameters" ] 1 => array:2 [ "identificador" => "cesec110" "titulo" => "Mesenteric microcirculation parameters" ] 2 => array:2 [ "identificador" => "cesec120" "titulo" => "Expression of mesenteric intercellular adhesion molecule 1 and the serum corticosterone levels" ] 3 => array:2 [ "identificador" => "cesec130" "titulo" => "Serum cytokine levels" ] ] ] 4 => array:2 [ "identificador" => "cesec140" "titulo" => "DISCUSSION" ] 5 => array:2 [ "identificador" => "cesec150" "titulo" => "AUTHOR CONTRIBUTIONS" ] 6 => array:2 [ "identificador" => "xack639282" "titulo" => "ACKNOWLEDGMENTS" ] 7 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-02-10" "fechaAceptado" => "2015-03-31" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "KEYWORDS" "identificador" => "xpalclavsec1582340" "palabras" => array:4 [ 0 => "Brain Death" 1 => "Autonomic Storm" 2 => "Microcirculation" 3 => "Intravital Microscopy" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "resumen" => "OBJECTIVES:Brain death is typically followed by autonomic changes that lead to hemodynamic instability, which is likely associated with microcirculatory dysfunction and inflammation. We evaluated the role of the microcirculation in the hemodynamic and inflammatory events that occur after brain death and the effects of autonomic storm inhibition via thoracic epidural blockade on mesenteric microcirculatory changes and inflammatory responses. METHODS:Male Wistar rats were anesthetized and mechanically ventilated. Brain death was induced via intracranial balloon inflation. Bupivacaine (brain death-thoracic epidural blockade group) or saline (brain death group) infusion via an epidural catheter was initiated immediately before brain death induction. Sham-operated animals were used as controls (SH group). The mesenteric microcirculation was analyzed via intravital microscopy, and the expression of adhesion molecules was evaluated via immunohistochemistry 180 min after brain death induction. RESULTS:A significant difference in mean arterial pressure behavior was observed between the brain death-thoracic epidural blockade group and the other groups, indicating that the former group experienced autonomic storm inhibition. However, the proportion of perfused small vessels in the brain death-thoracic epidural blockade group was similar to or lower than that in the brain death and SH groups, respectively. The expression of intercellular adhesion molecule 1 was similar between the brain death-thoracic epidural blockade and brain death groups but was significantly lower in the SH group than in the other two groups. The number of migrating leukocytes in the perivascular tissue followed the same trend for all groups. CONCLUSIONS:Although thoracic epidural blockade effectively inhibited the autonomic storm, it did not affect mesenteric hypoperfusion or inflammation induced by brain death." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "ceabs10" "titulo" => "OBJECTIVES:" ] 1 => array:2 [ "identificador" => "ceabs20" "titulo" => "METHODS:" ] 2 => array:2 [ "identificador" => "ceabs30" "titulo" => "RESULTS:" ] 3 => array:2 [ "identificador" => "ceabs40" "titulo" => "CONCLUSIONS:" ] ] ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "No potential conflict of interest was reported." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 423 "Ancho" => 788 "Tamanyo" => 37211 ] ] "descripcion" => array:1 [ "en" => "Mean arterial pressure of sham-operated rats (SH), brain-dead non-treated rats (BD), and brain-dead rats under thoracic epidural blockade (BD-TEB) 180 minutes after the surgical procedures. The animals were monitored over time. The data are presented as the means±SEM; ANOVA p<0.001; *p<0.05 vs. the other groups." ] ] 1 => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 640 "Ancho" => 788 "Tamanyo" => 145231 ] ] "descripcion" => array:1 [ "en" => "Intravital microscopy of the rat mesenteric microcirculation. A, The percentages of perfused small vessels (<30 μm) in sham-operated rats (SH), brain-dead non-treated rats (BD), and brain-dead rats under thoracic epidural blockade (BD-TEB) 180 min after the surgical procedures. The data are presented as the means±SEM; p ANOVA=0.002; *p<0.05 vs. the other groups. B, C, and D, Photomicrographs of mesenteric microvessels in the SH, BD, and BD-TEB groups, respectively." ] ] 2 => array:7 [ "identificador" => "fig3" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 282 "Ancho" => 789 "Tamanyo" => 28474 ] ] "descripcion" => array:1 [ "en" => "Expression of intercellular adhesion molecule (ICAM)-1 on mesenteric endothelial cells (p ANOVA <0.001) and the serum levels of corticosterone (p ANOVA=0.01) in sham-operated rats (SH), brain-dead non-treated rats (BD), and brain-dead rats under thoracic epidural blockade (BD-TEB) 180 min after the surgical procedures. The data are presented as the means±SEM. *p<0.05 vs. the other groups." ] ] 3 => array:7 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Rollers: leukocytes/5 min; Adhered: leukocytes/100 µm venule length; Migrated: leukocytes/5,000 µm2; WBC: White blood cells/mm3. SH: sham-operated rats; BD: brain-dead non-treated rats; BD-TEB: brain-dead rats under thoracic epidural blockade. These measurements were performed 180 min after the surgical procedures. The data are presented as the means±SEM. *p<0.01 vs. the other groups. **p<0.05 vs. the other groups." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">SH \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">BD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">BD-TEB \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">p ANOVA \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Rollers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">165 (12)* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">44 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">31 (5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Adherent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">6.9 (0.6)* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">4.5 (0.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">3.2 (0.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Migrated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">1.3 (0.2)** \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">2.5 (0.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">1.8 (0.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">WBC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">11,771 (1,122) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">10,450 (2,109) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">8,667 (1,196) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="middle">0.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "The results of the evaluation of the rat mesenteric microcirculation via intravital microscopy." ] ] 4 => array:7 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "SH: sham-operated rats; BD: brain-dead non-treated rats; BD-TEB: brain-dead rats under thoracic epidural blockade. These measurements were performed 180 min after the surgical procedures. The data are presented as the means±SEM." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">TNF-α (pg/mL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">IL-1β (pg/mL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">IL-6 (pg/mL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">IL-10 (pg/mL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">SH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.066±0.005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.102±0.017 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.131±0.022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.112±0.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">BD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.054±0.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.074±0.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.130±0.043 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.089±0.007 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">BD-TEB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.067±0.007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.090±0.017 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.151±0.043 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.096±0.010 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">p ANOVA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "The results of the evaluation of the serum cytokine levels via enzyme-linked immunosorbent assays." ] ] 5 => array:5 [ "identificador" => "fig4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 272 "Ancho" => 780 "Tamanyo" => 52620 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:35 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Endocrine changes and metabolic responses in a validated canine brain death model" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ HB Bittner \n \t\t\t\t\t\t\t\t """ 1 => """ SW Kendall \n \t\t\t\t\t\t\t\t """ 2 => """ EP Chen \n \t\t\t\t\t\t\t\t """ 3 => """ P Van Trigt \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/0883-9441(95)90017-9" "Revista" => array:7 [ "tituloSerie" => "J Crit Care" "fecha" => "1995" "volumen" => "10" "numero" => "2" "paginaInicial" => "56" "paginaFinal" => "63" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7647843" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/0883-9441(95)90017-9" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/0883-9441(95)90017-9" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systemic inflammation in the brain-dead organ donor" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ A Barklin \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1111/j.1399-6576.2008.01879.x" "Revista" => array:7 [ "tituloSerie" => "Acta Anaesthesiol Scand" "fecha" => "2009" "volumen" => "53" "numero" => "4" "paginaInicial" => "425" "paginaFinal" => "435" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19226294" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1111/j.1399-6576.2008.01879.x" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1111/aas.2009.53.issue-4" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brain death: repercussion on the organs and tissues" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ JM Domínguez-Roldán \n \t\t\t\t\t\t\t\t """ 1 => """ C García-Alfaro \n \t\t\t\t\t\t\t\t """ 2 => """ PI Jimenéz-González \n \t\t\t\t\t\t\t\t """ 3 => """ F Hernández-Hazañas \n \t\t\t\t\t\t\t\t """ 4 => """ ML Gascón Castillo \n \t\t\t\t\t\t\t\t """ 5 => """ JJ Egea Guerrero \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.medin.2009.03.008" "Revista" => array:7 [ "tituloSerie" => "Med Intensiva" "fecha" => "2009" "volumen" => "33" "numero" => "9" "paginaInicial" => "434" "paginaFinal" => "441" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19922825" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.medin.2009.03.008" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/j.medin.2009.03.008" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Improvement of donor myocardial function after treatment of autonomic storm during brain death" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ G Audibert \n \t\t\t\t\t\t\t\t """ 1 => """ C Charpentier \n \t\t\t\t\t\t\t\t """ 2 => """ C Seguin-Devaux \n \t\t\t\t\t\t\t\t """ 3 => """ PA Charretier \n \t\t\t\t\t\t\t\t """ 4 => """ H Grégoire \n \t\t\t\t\t\t\t\t """ 5 => """ Y Devaux \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1097/01.tp.0000235825.97538.d5" "Revista" => array:7 [ "tituloSerie" => "Transplantation" "fecha" => "2006" "volumen" => "82" "numero" => "8" "paginaInicial" => "1031" "paginaFinal" => "1036" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17060850" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1097/01.tp.0000235825.97538.d5" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1097/01.tp.0000235825.97538.d5" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ B Shivalkar \n \t\t\t\t\t\t\t\t """ 1 => """ J Van Loon \n \t\t\t\t\t\t\t\t """ 2 => """ W Wieland \n \t\t\t\t\t\t\t\t """ 3 => """ TB Tjandra-Maga \n \t\t\t\t\t\t\t\t """ 4 => """ M Borgers \n \t\t\t\t\t\t\t\t """ 5 => """ C Plets \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1161/01.cir.87.1.230" "Revista" => array:7 [ "tituloSerie" => "Circulation" "fecha" => "1993" "volumen" => "87" "numero" => "1" "paginaInicial" => "230" "paginaFinal" => "239" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8419012" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1161/01.cir.87.1.230" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1161/01.CIR.87.1.230" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Activation of proinflammatory mediators in heart transplants from brain-dead donors: evidence from a model of chronic rat cardiac allograft rejection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ MJ Wilhelm \n \t\t\t\t\t\t\t\t """ 1 => """ J Pratschke \n \t\t\t\t\t\t\t\t """ 2 => """ F Beato \n \t\t\t\t\t\t\t\t """ 3 => """ M Taal \n \t\t\t\t\t\t\t\t """ 4 => """ IA Laskowski \n \t\t\t\t\t\t\t\t """ 5 => """ DM Paz \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/s0041-1345(02)03283-9" "Revista" => array:7 [ "tituloSerie" => "Transplant Proc" "fecha" => "2002" "volumen" => "34" "numero" => "6" "paginaInicial" => "2359" "paginaFinal" => "2360" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12270436" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/s0041-1345(02)03283-9" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/S0041-1345(02)03283-9" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of brain death on organ quality and transplant outcome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ B Floerchinger \n \t\t\t\t\t\t\t\t """ 1 => """ R Oberhuber \n \t\t\t\t\t\t\t\t """ 2 => """ SG Tullius \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.trre.2011.10.001" "Revista" => array:7 [ "tituloSerie" => "Transplant Rev (Orlando)" "fecha" => "2012" "volumen" => "26" "numero" => "2" "paginaInicial" => "54" "paginaFinal" => "59" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22459036" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ R Simas \n \t\t\t\t\t\t\t\t """ 1 => """ P Sannomiya \n \t\t\t\t\t\t\t\t """ 2 => """ JW Cruz \n \t\t\t\t\t\t\t\t """ 3 => """ J Correia Cde \n \t\t\t\t\t\t\t\t """ 4 => """ FL Zanoni \n \t\t\t\t\t\t\t\t """ 5 => """ M Kase \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.6061/clinics/2012(sup01)13" "Revista" => array:7 [ "tituloSerie" => "Clinics" "fecha" => "2012" "volumen" => "67" "numero" => "1" "paginaInicial" => "69" "paginaFinal" => "75" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22584709" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.6061/clinics/2012(sup01)13" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.6061/clinics" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of autonomic storm by epidural anesthesia does not influence cardiac inflammatory response after brain death in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ IA Silva \n \t\t\t\t\t\t\t\t """ 1 => """ CJ Correia \n \t\t\t\t\t\t\t\t """ 2 => """ R Simas \n \t\t\t\t\t\t\t\t """ 3 => """ JW Cruz \n \t\t\t\t\t\t\t\t """ 4 => """ SG Ferreira \n \t\t\t\t\t\t\t\t """ 5 => """ FL Zanoni \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.transproceed.2012.07.108" "Revista" => array:7 [ "tituloSerie" => "Transplant Proc" "fecha" => "2012" "volumen" => "44" "numero" => "7" "paginaInicial" => "2213" "paginaFinal" => "2218" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22974957" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.transproceed.2012.07.108" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/j.transproceed.2012.07.108" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluating lung injury at increasing time intervals in a murine brain death model" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ S Wauters \n \t\t\t\t\t\t\t\t """ 1 => """ J Somers \n \t\t\t\t\t\t\t\t """ 2 => """ S De Vleeschauwer \n \t\t\t\t\t\t\t\t """ 3 => """ E Verbeken \n \t\t\t\t\t\t\t\t """ 4 => """ GM Verleden \n \t\t\t\t\t\t\t\t """ 5 => """ J van Loon \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.jss.2013.01.011" "Revista" => array:7 [ "tituloSerie" => "J Surg Res" "fecha" => "2013" "volumen" => "183" "numero" => "1" "paginaInicial" => "419" "paginaFinal" => "426" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23394934" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.jss.2013.01.011" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/j.jss.2013.01.011" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protective effects of labetalol on myocardial contractile function in brain-dead pigs" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ EM Siaghy \n \t\t\t\t\t\t\t\t """ 1 => """ P Halejcio-Delophont \n \t\t\t\t\t\t\t\t """ 2 => """ Y Devaux \n \t\t\t\t\t\t\t\t """ 3 => """ JP Richoux \n \t\t\t\t\t\t\t\t """ 4 => """ JP Villemot \n \t\t\t\t\t\t\t\t """ 5 => """ C Burlet \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/s0041-1345(98)00833-1" "Revista" => array:7 [ "tituloSerie" => "Transplant Proc" "fecha" => "1998" "volumen" => "30" "numero" => "6" "paginaInicial" => "2842" "paginaFinal" => "2843" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9745589" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/s0041-1345(98)00833-1" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/S0041-1345(98)00833-1" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Experimental treatment with beta blockers of hemodynamic and myocardial changes in organ donors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ R Ojeda-Rivero \n \t\t\t\t\t\t\t\t """ 1 => """ A Hernández-Fernández \n \t\t\t\t\t\t\t\t """ 2 => """ JM Dominguez-Roldán \n \t\t\t\t\t\t\t\t """ 3 => """ E Calderón \n \t\t\t\t\t\t\t\t """ 4 => """ M Ruiz \n \t\t\t\t\t\t\t\t """ 5 => """ E Lage \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/s0041-1345(01)02720-8" "Revista" => array:7 [ "tituloSerie" => "Transplant Proc" "fecha" => "2002" "volumen" => "34" "numero" => "1" "paginaInicial" => "185" "paginaFinal" => "186" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11959241" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/s0041-1345(01)02720-8" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/S0041-1345(01)02720-8" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Central sympathetic blockade ameliorates brain death-induced cardiotoxicity and associated changes in myocardial gene expression" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ T Yeh Jr \n \t\t\t\t\t\t\t\t """ 1 => """ AS Wechsler \n \t\t\t\t\t\t\t\t """ 2 => """ L Graham \n \t\t\t\t\t\t\t\t """ 3 => """ KE Loesser \n \t\t\t\t\t\t\t\t """ 4 => """ DA Sica \n \t\t\t\t\t\t\t\t """ 5 => """ L Wolfe \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1067/mtc.2002.124887" "Revista" => array:7 [ "tituloSerie" => "J Thorac Cardiovasc Surg" "fecha" => "2002" "volumen" => "124" "numero" => "6" "paginaInicial" => "1087" "paginaFinal" => "1098" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12447173" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1067/mtc.2002.124887" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1067/mtc.2002.124887" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevention of myocardial injury during brain death by total cardiac sympathectomy in the Chacma baboon" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ D Novitzky \n \t\t\t\t\t\t\t\t """ 1 => """ WN Wicomb \n \t\t\t\t\t\t\t\t """ 2 => """ DK Cooper \n \t\t\t\t\t\t\t\t """ 3 => """ AG Rose \n \t\t\t\t\t\t\t\t """ 4 => """ B Reichart \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/s0003-4975(10)63032-9" "Revista" => array:7 [ "tituloSerie" => "Ann Thorac Surg" "fecha" => "1986" "volumen" => "41" "numero" => "5" "paginaInicial" => "520" "paginaFinal" => "524" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3707246" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/s0003-4975(10)63032-9" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/S0003-4975(10)63032-9" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brain death impairs pancreatic microcirculation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ R Obermaier \n \t\t\t\t\t\t\t\t """ 1 => """ E von Dobschuetz \n \t\t\t\t\t\t\t\t """ 2 => """ T Keck \n \t\t\t\t\t\t\t\t """ 3 => """ HH Hopp \n \t\t\t\t\t\t\t\t """ 4 => """ O Drognitz \n \t\t\t\t\t\t\t\t """ 5 => """ W Schareck \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1046/j.1600-6143.2003.00317.x" "Revista" => array:7 [ "tituloSerie" => "Am J Transplant" "fecha" => "2004" "volumen" => "4" "numero" => "2" "paginaInicial" => "210" "paginaFinal" => "215" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14974941" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1046/j.1600-6143.2003.00317.x" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1046/j.1600-6143.2003.00317.x" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Synergistic effects of brain death and liver steatosis on the hepatic microcirculation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ K Yamagami \n \t\t\t\t\t\t\t\t """ 1 => """ J Hutter \n \t\t\t\t\t\t\t\t """ 2 => """ Y Yamamoto \n \t\t\t\t\t\t\t\t """ 3 => """ RJ Schauer \n \t\t\t\t\t\t\t\t """ 4 => """ G Enders \n \t\t\t\t\t\t\t\t """ 5 => """ R Leiderer \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1097/01.tp.0000167723.46580.78" "Revista" => array:7 [ "tituloSerie" => "Transplantation" "fecha" => "2005" "volumen" => "80" "numero" => "4" "paginaInicial" => "500" "paginaFinal" => "505" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16123725" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1097/01.tp.0000167723.46580.78" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1097/01.tp.0000167723.46580.78" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence of brain death and associated trauma on solid organ histological characteristics" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ R Simas \n \t\t\t\t\t\t\t\t """ 1 => """ DH Kogiso \n \t\t\t\t\t\t\t\t """ 2 => """ CJ Correia \n \t\t\t\t\t\t\t\t """ 3 => """ LF Silva \n \t\t\t\t\t\t\t\t """ 4 => """ IA Silva \n \t\t\t\t\t\t\t\t """ 5 => """ JW Cruz \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1590/s0102-86502012000700006" "Revista" => array:7 [ "tituloSerie" => "Acta Cir Bras" "fecha" => "2012" "volumen" => "27" "numero" => "7" "paginaInicial" => "465" "paginaFinal" => "470" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22760831" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1590/s0102-86502012000700006" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1590/S0102-86502012000700006" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Critical care management of potential organ donors: our current standard" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ C Dictus \n \t\t\t\t\t\t\t\t """ 1 => """ B Vienenkoetter \n \t\t\t\t\t\t\t\t """ 2 => """ M Esmaeilzadeh \n \t\t\t\t\t\t\t\t """ 3 => """ A Unterberg \n \t\t\t\t\t\t\t\t """ 4 => """ R Ahmadi \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1111/j.1399-0012.2009.01102.x" "Revista" => array:7 [ "tituloSerie" => "Clin Transplant" "fecha" => "2009" "volumen" => "23" "numero" => "Suppl 21" "paginaInicial" => "2" "paginaFinal" => "9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19930309" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1111/j.1399-0012.2009.01102.x" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1111/ctr.2009.23.issue-s21" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Graft-specific immune cells communicate inflammatory immune responses after brain death" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ B Floerchinger \n \t\t\t\t\t\t\t\t """ 1 => """ X Ge \n \t\t\t\t\t\t\t\t """ 2 => """ YL Lee \n \t\t\t\t\t\t\t\t """ 3 => """ A Jurisch \n \t\t\t\t\t\t\t\t """ 4 => """ RF Padera \n \t\t\t\t\t\t\t\t """ 5 => """ C Schmid \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.healun.2012.09.005" "Revista" => array:7 [ "tituloSerie" => "J Heart Lung Transplant" "fecha" => "2012" "volumen" => "31" "numero" => "12" "paginaInicial" => "1293" "paginaFinal" => "1300" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23102910" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.healun.2012.09.005" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/j.healun.2012.09.005" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brain death induced by cerebral haemorrhage - a new porcine model evaluated by CT angiography" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ CL Hvas \n \t\t\t\t\t\t\t\t """ 1 => """ TK Nielsen \n \t\t\t\t\t\t\t\t """ 2 => """ A Barklin \n \t\t\t\t\t\t\t\t """ 3 => """ JC S⊘rensen \n \t\t\t\t\t\t\t\t """ 4 => """ M Pedersen \n \t\t\t\t\t\t\t\t """ 5 => """ G Andersen \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1111/j.1399-6576.2012.02682.x" "Revista" => array:7 [ "tituloSerie" => "Acta Anaesthesiol Scand" "fecha" => "2012" "volumen" => "56" "numero" => "8" "paginaInicial" => "995" "paginaFinal" => "1005" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22409633" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1111/j.1399-6576.2012.02682.x" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1111/aas.2012.56.issue-8" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib21" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacological normalization of circulation after acute brain death" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ S Steen \n \t\t\t\t\t\t\t\t """ 1 => """ T Sjöberg \n \t\t\t\t\t\t\t\t """ 2 => """ Q Liao \n \t\t\t\t\t\t\t\t """ 3 => """ G Bozovic \n \t\t\t\t\t\t\t\t """ 4 => """ B Wohlfart \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1111/j.1399-6576.2012.02721.x" "Revista" => array:7 [ "tituloSerie" => "Acta Anaesthesiol Scand" "fecha" => "2012" "volumen" => "56" "numero" => "8" "paginaInicial" => "1006" "paginaFinal" => "1012" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22651688" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1111/j.1399-6576.2012.02721.x" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1111/aas.2012.56.issue-8" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib22" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of brain death and hemodynamic status on function and immunologic activation of the potential donor liver in the rat" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ JA van Der Hoeven \n \t\t\t\t\t\t\t\t """ 1 => """ GJ Ter Horst \n \t\t\t\t\t\t\t\t """ 2 => """ G Molema \n \t\t\t\t\t\t\t\t """ 3 => """ P de Vos \n \t\t\t\t\t\t\t\t """ 4 => """ AR Girbes \n \t\t\t\t\t\t\t\t """ 5 => """ F Postema \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1097/00000658-200012000-00009" "Revista" => array:7 [ "tituloSerie" => "Ann Surg" "fecha" => "2000" "volumen" => "232" "numero" => "6" "paginaInicial" => "804" "paginaFinal" => "813" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11088075" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1097/00000658-200012000-00009" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1097/00000658-200012000-00009" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib23" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protective effects of urinary trypsin inhibitor (UTI) on hepatic microvasculature in hypotensive brain-dead rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ K Itabashi \n \t\t\t\t\t\t\t\t """ 1 => """ Y Ito \n \t\t\t\t\t\t\t\t """ 2 => """ T Takahashi \n \t\t\t\t\t\t\t\t """ 3 => """ K Ishii \n \t\t\t\t\t\t\t\t """ 4 => """ K Sato \n \t\t\t\t\t\t\t\t """ 5 => """ A Kakita \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1159/000063074" "Revista" => array:7 [ "tituloSerie" => "Eur Surg Res" "fecha" => "2002" "volumen" => "34" "numero" => "4" "paginaInicial" => "330" "paginaFinal" => "338" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12145560" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1159/000063074" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1159/000063074" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib24" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relationship between duration of brain death and hemodynamic (in)stability on progressive dysfunction and increased immunologic activation of donor kidneys" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ JA van der Hoeven \n \t\t\t\t\t\t\t\t """ 1 => """ G Molema \n \t\t\t\t\t\t\t\t """ 2 => """ GJ Ter Horst \n \t\t\t\t\t\t\t\t """ 3 => """ RL Freund \n \t\t\t\t\t\t\t\t """ 4 => """ J Wiersema \n \t\t\t\t\t\t\t\t """ 5 => """ R van Schilfgaarde \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1046/j.1523-1755.2003.00272.x" "Revista" => array:7 [ "tituloSerie" => "Kidney Int" "fecha" => "2003" "volumen" => "64" "numero" => "5" "paginaInicial" => "1874" "paginaFinal" => "1882" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14531823" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1046/j.1523-1755.2003.00272.x" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1046/j.1523-1755.2003.00272.x" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib25" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Carbon monoxide inhalation ameliorates conditions of lung grafts from rat brain death donors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ HC Zhou \n \t\t\t\t\t\t\t\t """ 1 => """ WG Ding \n \t\t\t\t\t\t\t\t """ 2 => """ XG Cui \n \t\t\t\t\t\t\t\t """ 3 => """ P Pan \n \t\t\t\t\t\t\t\t """ 4 => """ B Zhang \n \t\t\t\t\t\t\t\t """ 5 => """ WZ Li \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Chin Med J (Engl)" "fecha" => "2008" "volumen" => "121" "numero" => "15" "paginaInicial" => "1411" "paginaFinal" => "1419" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18959119" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib26" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Detrimental consequences of brain injury on peripheral cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ A Catania \n \t\t\t\t\t\t\t\t """ 1 => """ C Lonati \n \t\t\t\t\t\t\t\t """ 2 => """ A Sordi \n \t\t\t\t\t\t\t\t """ 3 => """ S Gatti \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.bbi.2009.04.006" "Revista" => array:7 [ "tituloSerie" => "Brain Behav Immun" "fecha" => "2009" "volumen" => "23" "numero" => "7" "paginaInicial" => "877" "paginaFinal" => "884" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19394418" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.bbi.2009.04.006" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/j.bbi.2009.04.006" ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib27" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brain death induces inflammation in the donor intestine" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ LG Koudstaal \n \t\t\t\t\t\t\t\t """ 1 => """ NA ‘t Hart \n \t\t\t\t\t\t\t\t """ 2 => """ PJ Ottens \n \t\t\t\t\t\t\t\t """ 3 => """ A van den Berg \n \t\t\t\t\t\t\t\t """ 4 => """ RJ Ploeg \n \t\t\t\t\t\t\t\t """ 5 => """ H van Goor \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1097/TP.0b013e31817ba53a" "Revista" => array:7 [ "tituloSerie" => "Transplantation" "fecha" => "2008" "volumen" => "86" "numero" => "1" "paginaInicial" => "148" "paginaFinal" => "154" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18622292" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1097/TP.0b013e31817ba53a" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1097/TP.0b013e31817ba53a" ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib28" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Time-dependent changes in donor brain death related processes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ TA Schuurs \n \t\t\t\t\t\t\t\t """ 1 => """ AM Morariu \n \t\t\t\t\t\t\t\t """ 2 => """ PJ Ottens \n \t\t\t\t\t\t\t\t """ 3 => """ NA ‘t Hart \n \t\t\t\t\t\t\t\t """ 4 => """ SH Popma \n \t\t\t\t\t\t\t\t """ 5 => """ HG Leuvenink \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1111/j.1600-6143.2006.01547.x" "Revista" => array:7 [ "tituloSerie" => "Am J Transplant" "fecha" => "2006" "volumen" => "6" "numero" => "12" "paginaInicial" => "2903" "paginaFinal" => "2911" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17062004" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1111/j.1600-6143.2006.01547.x" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1111/ajt.2006.6.issue-12" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib29" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brain death and its influence on donor organ quality and outcome after transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ J Pratschke \n \t\t\t\t\t\t\t\t """ 1 => """ MJ Wilhelm \n \t\t\t\t\t\t\t\t """ 2 => """ M Kusaka \n \t\t\t\t\t\t\t\t """ 3 => """ M Basker \n \t\t\t\t\t\t\t\t """ 4 => """ DK Cooper \n \t\t\t\t\t\t\t\t """ 5 => """ WW Hancock \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1097/00007890-199902150-00001" "Revista" => array:7 [ "tituloSerie" => "Transplantation" "fecha" => "1999" "volumen" => "67" "numero" => "3" "paginaInicial" => "343" "paginaFinal" => "348" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10030276" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1097/00007890-199902150-00001" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1097/00007890-199902150-00001" ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib30" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brain death and its impact on the donor heart-lessons from animal models" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ MJ Wilhelm \n \t\t\t\t\t\t\t\t """ 1 => """ J Pratschke \n \t\t\t\t\t\t\t\t """ 2 => """ IA Laskowski \n \t\t\t\t\t\t\t\t """ 3 => """ DM Paz \n \t\t\t\t\t\t\t\t """ 4 => """ NL Tilney \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/s1053-2498(00)00073-5" "Revista" => array:7 [ "tituloSerie" => "J Heart Lung Transplant" "fecha" => "2000" "volumen" => "19" "numero" => "5" "paginaInicial" => "414" "paginaFinal" => "418" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10808147" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/s1053-2498(00)00073-5" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/S1053-2498(00)00073-5" ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib31" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The microcirculation and inflammation: site of action for glucocorticoids" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ M Perretti \n \t\t\t\t\t\t\t\t """ 1 => """ A Ahluwalia \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Microcirculation" "fecha" => "2000" "volumen" => "7" "numero" => "3" "paginaInicial" => "147" "paginaFinal" => "161" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1111/micc.2000.7.issue-3" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib32" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Microvascular blood flow is altered in patients with sepsis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ D De Backer \n \t\t\t\t\t\t\t\t """ 1 => """ J Creteur \n \t\t\t\t\t\t\t\t """ 2 => """ JC Preiser \n \t\t\t\t\t\t\t\t """ 3 => """ MJ Dubois \n \t\t\t\t\t\t\t\t """ 4 => """ JL Vincent \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1164/rccm.200109-016oc" "Revista" => array:7 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2002" "volumen" => "166" "numero" => "1" "paginaInicial" => "98" "paginaFinal" => "104" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12091178" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1164/rccm.200109-016oc" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1164/rccm.200109-016OC" ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib33" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Microcirculatory alterations: potential mechanisms and implications for therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ D De Backer \n \t\t\t\t\t\t\t\t """ 1 => """ K Donadello \n \t\t\t\t\t\t\t\t """ 2 => """ FS Taccone \n \t\t\t\t\t\t\t\t """ 3 => """ G Ospina-Tascon \n \t\t\t\t\t\t\t\t """ 4 => """ D Salgado \n \t\t\t\t\t\t\t\t """ 5 => """ JL Vincent \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1186/2110-5820-1-27" "Revista" => array:6 [ "tituloSerie" => "Ann Intensive Care" "fecha" => "2011" "volumen" => "1" "numero" => "1" "paginaInicial" => "27" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21906380" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1186/2110-5820-1-27" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1186/2110-5820-1-27" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib34" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Decreased capillary density in?vivo in bowel mucosa of rats with normotensive sepsis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ I Farquhar \n \t\t\t\t\t\t\t\t """ 1 => """ CM Martin \n \t\t\t\t\t\t\t\t """ 2 => """ C Lam \n \t\t\t\t\t\t\t\t """ 3 => """ R Potter \n \t\t\t\t\t\t\t\t """ 4 => """ CG Ellis \n \t\t\t\t\t\t\t\t """ 5 => """ WJ Sibbald \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1006/jsre.1996.0103" "Revista" => array:7 [ "tituloSerie" => "J Surg Res" "fecha" => "1996" "volumen" => "61" "numero" => "1" "paginaInicial" => "190" "paginaFinal" => "196" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8769965" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1006/jsre.1996.0103" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1006/jsre.1996.0103" ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib35" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ Y Sakr \n \t\t\t\t\t\t\t\t """ 1 => """ MJ Dubois \n \t\t\t\t\t\t\t\t """ 2 => """ D De Backer \n \t\t\t\t\t\t\t\t """ 3 => """ J Creteur \n \t\t\t\t\t\t\t\t """ 4 => """ JL Vincent \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1097/01.ccm.0000138558.16257.3f" "Revista" => array:7 [ "tituloSerie" => "Crit Care Med" "fecha" => "2004" "volumen" => "32" "numero" => "9" "paginaInicial" => "1825" "paginaFinal" => "1831" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15343008" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1097/01.ccm.0000138558.16257.3f" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1097/01.CCM.0000138558.16257.3F" ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack639282" "titulo" => "ACKNOWLEDGMENTS" "texto" => "This research was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Grant number 09/10759-9." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/18075932/0000007000000006/v1_202212011416/S1807593222013758/v1_202212011416/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/18075932/0000007000000006/v1_202212011416/S1807593222013758/v1_202212011416/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222013758?idApp=UINPBA00004N"]

Statistics

BASIC RESEARCH

Rafael Simas, Sueli G Ferreira, Laura Menegat, Fernando L Zanoni, Cristiano J Correia, Isaac A Silva, Paulina Sannomiya, Luiz F P Moreira

Corresponding author

luiz.moreira@incor.usp.br

Luiz F P Moreira Corresponding author:

Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM-11), São Paulo/SP, Brazil

Read

762

Times
was read the article

234

Total PDF

528

Total HTML

Share statistics

 array:24 [
  "pii" => "S1807593222013758"
  "issn" => "18075932"
  "doi" => "10.6061/clinics/2015(06)11"
  "estado" => "S300"
  "fechaPublicacion" => "2015-06-01"
  "aid" => "1375"
  "copyright" => "CLINICS"
  "copyrightAnyo" => "2015"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/"
  "subdocumento" => "fla"
  "cita" => "Clinics. 2015;70:446-52"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S180759322201376X"
    "issn" => "18075932"
    "doi" => "10.6061/clinics/2015(06)12"
    "estado" => "S300"
    "fechaPublicacion" => "2015-06-01"
    "aid" => "1376"
    "copyright" => "CLINICS"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/"
    "subdocumento" => "fla"
    "cita" => "Clinics. 2015;70:453-9"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">REVIEW</span>"
      "titulo" => "Risk of congenital anomalies associated with antithyroid treatment during pregnancy&#58; a meta-analysis"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "453"
          "paginaFinal" => "459"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig1"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 724
              "Ancho" => 792
              "Tamanyo" => 46543
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Flow chart of the literature search and article selection&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Xiang Li, Gui-Yang Liu, Jian-Li Ma, Liang Zhou"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Xiang"
              "apellidos" => "Li"
            ]
            1 => array:2 [
              "nombre" => "Gui-Yang"
              "apellidos" => "Liu"
            ]
            2 => array:2 [
              "nombre" => "Jian-Li"
              "apellidos" => "Ma"
            ]
            3 => array:2 [
              "nombre" => "Liang"
              "apellidos" => "Zhou"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S180759322201376X?idApp=UINPBA00004N"
    "url" => "/18075932/0000007000000006/v1_202212011416/S180759322201376X/v1_202212011416/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S1807593222013746"
    "issn" => "18075932"
    "doi" => "10.6061/clinics/2015(06)10"
    "estado" => "S300"
    "fechaPublicacion" => "2015-06-01"
    "aid" => "1374"
    "copyright" => "CLINICS"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/"
    "subdocumento" => "fla"
    "cita" => "Clinics. 2015;70:441-5"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">CLINICAL SCIENCE</span>"
      "titulo" => "Assessments of the associations of thrombus localization with accompanying disorders&#44; risk factors&#44; D-dimer levels&#44; and the red cell distribution width in pulmonary embolism"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "441"
          "paginaFinal" => "445"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig2"
          "etiqueta" => "Figure 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 650
              "Ancho" => 780
              "Tamanyo" => 34576
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristic curve of red blood cell distribution width for predicting the presence of main pulmonary arteries thrombus in studied patients&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Aysel Sunnetcioglu, Bunyamin Sertogullarindan, Bulent Ozbay, Selvi Asker, Salemi Ekin"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "Aysel"
              "apellidos" => "Sunnetcioglu"
            ]
            1 => array:2 [
              "nombre" => "Bunyamin"
              "apellidos" => "Sertogullarindan"
            ]
            2 => array:2 [
              "nombre" => "Bulent"
              "apellidos" => "Ozbay"
            ]
            3 => array:2 [
              "nombre" => "Selvi"
              "apellidos" => "Asker"
            ]
            4 => array:2 [
              "nombre" => "Salemi"
              "apellidos" => "Ekin"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222013746?idApp=UINPBA00004N"
    "url" => "/18075932/0000007000000006/v1_202212011416/S1807593222013746/v1_202212011416/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">BASIC RESEARCH</span>"
    "titulo" => "Mesenteric hypoperfusion and inflammation induced by brain death are not affected by inhibition of the autonomic storm in rats"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "446"
        "paginaFinal" => "452"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Rafael Simas, Sueli G Ferreira, Laura Menegat, Fernando L Zanoni, Cristiano J Correia, Isaac A Silva, Paulina Sannomiya, Luiz F P Moreira"
        "autores" => array:8 [
          0 => array:2 [
            "nombre" => "Rafael"
            "apellidos" => "Simas"
          ]
          1 => array:2 [
            "nombre" => "Sueli G"
            "apellidos" => "Ferreira"
          ]
          2 => array:2 [
            "nombre" => "Laura"
            "apellidos" => "Menegat"
          ]
          3 => array:2 [
            "nombre" => "Fernando L"
            "apellidos" => "Zanoni"
          ]
          4 => array:2 [
            "nombre" => "Cristiano J"
            "apellidos" => "Correia"
          ]
          5 => array:2 [
            "nombre" => "Isaac A"
            "apellidos" => "Silva"
          ]
          6 => array:2 [
            "nombre" => "Paulina"
            "apellidos" => "Sannomiya"
          ]
          7 => array:4 [
            "nombre" => "Luiz F P"
            "apellidos" => "Moreira"
            "email" => array:1 [
              0 => "luiz.moreira@incor.usp.br"
            ]
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "&#42;"
                "identificador" => "cor1"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:2 [
            "entidad" => "Instituto do Cora&#231;&#227;o &#40;InCor&#41; do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo&#44; Laboratory of Cardiovascular Surgery and Circulation Pathophysiology &#40;LIM-11&#41;&#44; S&#227;o Paulo&#47;SP&#44; Brazil"
            "identificador" => "aff1"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor1"
            "etiqueta" => "&#42;"
            "correspondencia" => "Luiz F P Moreira Corresponding author&#58;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig2"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 640
            "Ancho" => 788
            "Tamanyo" => 145231
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Intravital microscopy of the rat mesenteric microcirculation&#46; A&#44; The percentages of perfused small vessels &#40;&#60;30 &#956;m&#41; in sham-operated rats &#40;SH&#41;&#44; brain-dead non-treated rats &#40;BD&#41;&#44; and brain-dead rats under thoracic epidural blockade &#40;BD-TEB&#41; 180 min after the surgical procedures&#46; The data are presented as the means&#177;SEM&#59; p ANOVA&#61;0&#46;002&#59; &#42;<span class="elsevierStyleItalic">p</span>&#60;0&#46;05 vs&#46; the other groups&#46; B&#44; C&#44; and D&#44; Photomicrographs of mesenteric microvessels in the SH&#44; BD&#44; and BD-TEB groups&#44; respectively&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Organ transplantation is a unique treatment alternative for many critically ill patients&#44; and one major source of organs is brain-dead patients&#46; Brain death &#40;BD&#41; induces a series of hemodynamic&#44; hormonal&#44; and inflammatory alterations that can deteriorate the viability of organs <a class="elsevierStyleCrossRef" href="#bib1">1</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib3">3</a>&#46;</p><p id="para20" class="elsevierStylePara elsevierViewall">Parasympathetic activation associated with progressive bradycardia and hypotension is generally observed after the initial trauma that leads to BD&#46; If the injury involves the most distal midbrain&#44; the vagal cardiac motor center is destroyed&#44; and parasympathetic activity is stopped&#46; As a consequence&#44; sympathetic activity is not regulated by the parasympathetic system&#44; resulting in a classical autonomic storm characterized by tachycardia and hypertension&#46; Finally&#44; a profound reduction in sympathetic outflow leads to hemodynamic instability exacerbated by hypovolemia&#44; dysregulation of the peripheral vasculature&#44; and vasodilatation <a class="elsevierStyleCrossRef" href="#bib4">4</a>&#46;</p><p id="para30" class="elsevierStylePara elsevierViewall">In animal models of BD&#44; a balloon catheter placed in the intracranial cavity is inflated to increase the local pressure&#44; leading to an immediate increase in the norepinephrine and epinephrine concentrations&#44; which are associated with tachycardia and hypertension followed by vasoplegia and hypotension <a class="elsevierStyleCrossRef" href="#bib5">5</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib7">7</a>&#46; The prompt appearance of a hypertensive peak followed by an immediate decrease in arterial blood pressure below the baseline level has been observed in models of rapidly increasing intracranial pressure <a class="elsevierStyleCrossRef" href="#bib8">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib9">9</a>&#46; Alternatively&#44; models of slowly increasing intracranial pressure show a gradual elevation of mean arterial pressure&#44; which is also followed by a hypotensive episode <a class="elsevierStyleCrossRef" href="#bib10">10</a>&#46;</p><p id="para40" class="elsevierStylePara elsevierViewall">Controversial effects documented using different methods of autonomic storm inhibition hamper the understanding of the influence of sympathetic activity on transplantable organs&#46; Administering intravenous propranolol&#44; xylazine&#44; and labetalol <a class="elsevierStyleCrossRef" href="#bib11">11</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib13">13</a> inhibits the sudden increase in mean arterial pressure after BD induction&#44; resulting in decreased damage to the myocardial tissue and reduced production of multiple myocardial gene products&#46; In contrast&#44; in a surgical model of sympathectomy in baboons&#44; Novitzky et al&#46; <a class="elsevierStyleCrossRef" href="#bib14">14</a> found that this procedure did not abolish the hypertensive crisis&#44; indicating that the performance of this surgical procedure is not sufficient to block the autonomic storm&#46; In addition&#44; Silva et al&#46; <a class="elsevierStyleCrossRef" href="#bib9">9</a> demonstrated that thoracic epidural anesthesia effectively blocks the autonomic storm but does not alter the expression of inflammatory mediators in the myocardial tissue&#46;</p><p id="para50" class="elsevierStylePara elsevierViewall">The hemodynamic instability observed in BD is generally associated with ischemia and tissue hypoperfusion&#44; which compromise the viability of the organs that are suitable for transplantation <a class="elsevierStyleCrossRef" href="#bib2">2</a>&#46; Previous studies have shown that BD leads to substantial impairment of microcirculation in the liver and the pancreas <a class="elsevierStyleCrossRef" href="#bib15">15</a>&#44;<a class="elsevierStyleCrossRef" href="#bib16">16</a>&#46; Furthermore&#44; our group observed similar alterations triggered by BD in the rat mesenteric microcirculation <a class="elsevierStyleCrossRef" href="#bib8">8</a>&#46; In particular&#44; mesenteric hypoperfusion immediately occurred after BD induction&#44; and this phenomenon persisted for up to three hours thereafter&#46; This hypoperfusion was associated with elevated expression of endothelial cell adhesion molecules and increased leukocyte migration to the perivascular tissues such as in mesentery&#44; lung&#44; and liver tissue <a class="elsevierStyleCrossRef" href="#bib8">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib17">17</a>&#46;</p><p id="para60" class="elsevierStylePara elsevierViewall">Despite the clear importance of the microcirculation for optimizing the therapy for circulatory shock of various etiologies&#44; the influence of autonomic storm blockade on microcirculatory changes after BD has not been investigated&#46; Therefore&#44; the present study was conducted to assess the role of the microcirculation in hemodynamic and inflammatory events that occur after BD induction and to investigate the effects of sympathetic system inhibition via thoracic epidural anesthesia&#46; Microcirculatory changes&#44; including perfusion and leukocyte-endothelial interactions&#44; were analyzed via intravital microscopy of the mesentery&#46; Local and systemic inflammatory markers were also evaluated&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">MATERIAL AND METHODS</span><p id="para70" class="elsevierStylePara elsevierViewall">Male Wistar rats &#40;300&#177;50 g&#41; were used according to experimental protocols approved by the Animal Subject Committee of the Instituto do Cora&#231;&#227;o &#40;InCor&#41; do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo&#46; The animals were randomly allocated to three groups&#58; sham-operated &#40;SH group&#44; n&#61;12&#41;&#44; brain-dead non-treated &#40;BD group&#44; n&#61;12&#41;&#44; and brain-dead under thoracic epidural blockade &#40;TEB&#41; &#40;BD-TEB group&#44; n&#61;12&#41;&#46; The animals were evaluated 180 min after the conclusion of the surgical procedures&#46;</p><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Brain death model and thoracic epidural anesthesia</span><p id="para80" class="elsevierStylePara elsevierViewall">All animals were anesthetized in a chamber using isoflurane &#40;5&#37;&#41;&#44; intubated&#44; and mechanically ventilated &#40;Harvard Apparatus&#44; Holliston&#44; MA&#44; USA&#41; with 100&#37; FiO<span class="elsevierStyleInf">2</span> &#40;tidal volume&#58; 10 mL&#47;kg&#44; 70 breaths&#47;min&#41;&#46; Sedation was maintained via continuous inhalation of 2&#37; isoflurane&#46; The carotid artery was cannulated for blood pressure monitoring and blood sampling&#46; The jugular vein was cannulated for continuous infusion of saline solution &#40;2 mL&#47;h&#41; to minimize dehydration&#46; No intravenous drugs were administered&#46;</p><p id="para90" class="elsevierStylePara elsevierViewall">BD induction was performed as previously described <a class="elsevierStyleCrossRef" href="#bib9">9</a>&#44;<a class="elsevierStyleCrossRef" href="#bib17">17</a>&#46; Briefly&#44; a Fogarty 4-French catheter &#40;Baxter Health Care&#44; Deerfield&#44; IL&#44; USA&#41; was placed in the intracranial cavity through a drilled parietal burr hole&#46; The balloon catheter was rapidly inflated with 0&#46;5 mL of saline solution to increase the intracranial pressure until BD was confirmed based on maximal pupil dilatation and the absence of the corneal and respiratory reflexes&#46; Anesthesia with isoflurane was discontinued after BD induction&#46;</p><p id="para100" class="elsevierStylePara elsevierViewall">A 10-French polyethylene catheter was placed in the epidural space through an incision over the T11&#8211;L1 vertebrae and was advanced to the T5 level&#46; The BD-TEB group received a bolus infusion of 20 &#181;L of 0&#46;5&#37; bupivacaine 5 min before BD induction&#44; followed by continuous infusion &#40;15 &#181;L&#47;h&#41; for 3 h&#46; The animals in the BD group were administered equivalent volumes of saline solution&#46; No drugs were administered to the rats in the SH group&#46;</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Blood gas&#44; electrolyte&#44; and lactate measurements and white blood cell counts</span><p id="para110" class="elsevierStylePara elsevierViewall">The blood gas&#44; electrolyte&#44; and lactate levels were measured in blood samples obtained from the carotid artery at baseline &#40;0 min&#41; and 180 min after the surgical procedures using a gas analyzer &#40;Radiometer ABL 555&#44; Radiometer Medical&#44; Copenhagen&#44; Denmark&#41;&#46; White blood cell &#40;WBC&#41; counts were determined in blood samples obtained from the cut tip of the tail vein at the same time points&#46; The total WBC counts were determined using a Neubauer chamber&#46; Differential cell counting was performed on stained films via oil immersion microscopy&#46; A total of 100 cells were counted and classified according to standard morphological criteria&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Intravital microscopy of the mesenteric microcirculation</span><p id="para120" class="elsevierStylePara elsevierViewall">Intravital microscopy of the mesenteric microcirculation was performed as previously described <a class="elsevierStyleCrossRef" href="#bib8">8</a>&#46; Briefly&#44; an abdominal midline incision was performed 180 min after BD induction&#44; and the distal ileum and its accompanying mesentery were exposed for in vivo microscopic examination of the microcirculation&#46; The animals were maintained on a specially designed stage warmed with circulating 37&#176;C water&#46; The mesentery was continuously perfused with warm &#40;37&#176;C&#41; Krebs-Henseleit solution saturated with a mixture of gases &#40;95&#37; N<span class="elsevierStyleInf">2</span> and 5&#37; CO<span class="elsevierStyleInf">2</span>&#41;&#46; A color camera &#40;AxioCam HSc&#44; Carl Zeiss&#44; M&#252;nchen-Hallbergmos&#44; Germany&#41; was connected to a triocular microscope &#40;Axioplan 2&#44; Carl Zeiss&#41;&#44; and the microcirculatory variables were analyzed using Axiovision 4&#46;1 imaging software &#40;Carl Zeiss&#41;&#46; The vascular density in a 1-mm<span class="elsevierStyleSup">2</span> area on the computer screen was assessed using a 10x light microscope objective&#46; The flow&#44; defined as continuous or intermittent&#47;absent&#44; was analyzed in vessels with a diameter &#60;30 &#181;m&#46; Five fields of view were selected for each animal&#46; To evaluate leukocyte-endothelial interactions&#44; three post-capillary venules with diameters ranging from 15 to 25 &#181;m were selected for each animal&#46; The number of rolling leukocytes was calculated as the mean number of WBCs passing a designated line perpendicular to the venular axis per 5 min&#46; The adherent cells &#40;i&#46;e&#46;&#44; leukocytes that remained stationary on the venular endothelium for more than 30 s&#41; were counted in a 100 &#181;m segment of the vessel&#46; The number of leukocytes that accumulated in the connective tissue adjacent to the selected post-capillary venule was determined in a standard area of 5&#44;000 &#181;m<span class="elsevierStyleSup">2</span>&#46; Three fields of view for each microvessel were examined&#46;</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">Evaluation of intercellular adhesion molecule 1 expression via immunohistochemistry</span><p id="para130" class="elsevierStylePara elsevierViewall">The animals were exsanguinated from the abdominal aorta&#44; and the mesentery was removed&#44; immersed in hexane&#44; and frozen in liquid nitrogen&#46; Serial slices of the mesentery &#40;8 &#181;m&#41; were placed on glass slides coated with organosilane &#40;Sigma Chemical Co&#46;&#44; St&#46; Louis&#44; MO&#44; USA&#41;&#46; The samples were fixed in acetone&#44; and SuperBlock buffer &#40;Pierce Biotechnology&#44; Rockford&#44; IL&#44; USA&#41; was used to block nonspecific sites&#46; For the immunodetection of intercellular adhesion molecule 1 &#40;ICAM-1&#41; on mesenteric microvessels&#44; tissue sections were incubated overnight at 4&#176;C in a biotin-conjugated anti-rat ICAM-1 &#40;CD54&#41; monoclonal antibody &#40;Seikagaku&#44; Tokyo&#44; Japan&#41; diluted 1&#58;50 in phosphate-buffered saline &#40;PBS&#41; containing 0&#46;3&#37; Tween-20&#46; After washing the slides with PBS&#44; the sections were incubated for 1 h at room temperature in streptavidin-fluorescein &#40;Amersham Pharmacia Biotech&#44; London&#44; UK&#41; diluted 1&#58;200 in PBS&#46; After washing with PBS&#44; the samples were treated with Vectashield mounting medium containing propidium iodide &#40;Vector Laboratories&#44; Burlingame&#44; CA&#44; USA&#41; to preserve their fluorescence&#46; The system used for image acquisition included a DS-Ri1 digital camera &#40;Nikon&#44; Tokyo&#44; Japan&#41; connected to a fluorescence microscope &#40;Nikon&#41; controlled with NIS-Elements-BR software &#40;Nikon&#41;&#46; The results are presented as the mean fluorescence intensity&#46;</p></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">Serum concentrations of cytokines and corticosterone</span><p id="para140" class="elsevierStylePara elsevierViewall">Blood samples obtained from the abdominal aorta were centrifuged &#40;1&#44;500 g&#44; 25&#176;C&#41;&#44; and the serum concentrations of tumor necrosis factor-&#945; &#40;TNF-&#945;&#41;&#44; interleukin &#40;IL&#41;-1&#946;&#44; IL-6&#44; IL-10&#44; and corticosterone were determined using enzyme-linked immunosorbent assay &#40;ELISA&#41; kits as recommended by the manufacturers &#40;cytokines&#58; R&#38;D Systems&#44; Minneapolis&#44; MN&#44; USA&#59; corticosterone&#58; Cayman Chemical&#44; Ann Arbor&#44; MI&#44; USA&#41;&#46;</p></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">Statistical analysis</span><p id="para150" class="elsevierStylePara elsevierViewall">All data are presented as the means &#177; standard error of the mean &#40;SEM&#41;&#46; The overall group differences were compared via two-way analysis of variance &#40;ANOVA&#41; using group and time as the factors followed by a post hoc Bonferroni test or via a one-way ANOVA followed by a post hoc Bonferroni test&#46; Adjusted p values for multiple comparisons were calculated&#44; and a <span class="elsevierStyleItalic">p</span>-value of &#60;0&#46;05 was considered to indicate statistical significance&#46; All statistical analyses were performed using Graph-Pad Prism 6&#46;1&#46;</p></span></span><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">RESULTS</span><span id="cesec100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle150">Hemodynamic parameters</span><p id="para160" class="elsevierStylePara elsevierViewall">The rats in the BD group exhibited a sudden increase in mean arterial pressure over the first minute following catheter inflation&#46; In contrast&#44; the rats treated with TEB did not exhibit this hypertensive episode after BD induction&#46; The mean arterial pressure then decreased below the baseline level in both groups&#46; After 75 min&#44; the mean arterial pressure was restored to normal levels&#44; and no difference in mean arterial pressure was observed between the groups&#46; In the SH rats&#44; the mean arterial pressure did not change over time &#40;<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>&#41;&#46; There were no significant differences in the arterial blood gas&#44; electrolyte&#44; or lactate levels between the groups &#40;data not shown&#41;&#46;</p><elsevierMultimedia ident="fig1"></elsevierMultimedia></span><span id="cesec110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle160">Mesenteric microcirculation parameters</span><p id="para170" class="elsevierStylePara elsevierViewall">The average proportion of perfused small vessels in the BD group was 39&#37; compared to 74&#37; in the SH rats&#46; The treatment of BD rats with TEB did not alter mesenteric hypoperfusion &#40;43&#37;&#41;&#44; as illustrated in <a class="elsevierStyleCrossRef" href="#fig2">Figure 2</a> and the supplementary videos&#46;</p><elsevierMultimedia ident="fig2"></elsevierMultimedia><p id="para180" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="fig4"></elsevierMultimedia></p><p id="para190" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a> shows the leukocyte-endothelium interaction data obtained from perfused small vessels&#46; Similar results were observed in both the BD and BD-TEB rats&#44; and the number of rolling leukocytes in these two groups was reduced compared to that in the SH group&#46; A reduction in the number of adherent leukocytes in the BD and BD-TEB groups compared to the SH group was also observed&#46; In contrast&#44; the number of migrating leukocytes in both groups of BD rats was higher than that in the SH group&#46; These results were not accompanied by significant changes in the number of WBCs&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia></span><span id="cesec120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle170">Expression of mesenteric intercellular adhesion molecule 1 and the serum corticosterone levels</span><p id="para200" class="elsevierStylePara elsevierViewall">The expression of ICAM-1 was investigated in the mesentery of rats that were not examined via intravital microscopy &#40;<a class="elsevierStyleCrossRef" href="#fig3">Figure 3</a>&#41;&#46; The levels of ICAM-1 expression were similar between the BD and BD-TEB groups and exceeded those in the SH group&#46; The serum levels of corticosterone were reduced in the BD and BD-TEB groups compared to the SH group three hours after BD induction &#40;<a class="elsevierStyleCrossRef" href="#fig3">Figure 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig3"></elsevierMultimedia></span><span id="cesec130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle180">Serum cytokine levels</span><p id="para210" class="elsevierStylePara elsevierViewall">Similar increases in the serum concentrations of TNF-&#945;&#44; IL-1&#946;&#44; IL-6&#44; and IL-10 were observed in the BD&#44; BD-TEB&#44; and SH groups 180 min after the surgical procedures&#46; The reference values obtained in Naive rats were below the limit of detection of the assay&#46; These results are summarized in <a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl2"></elsevierMultimedia></span></span><span id="cesec140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle190">DISCUSSION</span><p id="para220" class="elsevierStylePara elsevierViewall">In an attempt to attenuate the hemodynamic alterations triggered by BD&#44; thoracic sympathetic blockade was induced in this study via epidural anesthesia with bupivacaine&#46; We found that TEB effectively abolished the hypertensive event observed after BD induction but did not affect the following hypotensive episode&#46; Furthermore&#44; mesenteric hypoperfusion and inflammation&#44; characterized by increased leukocyte migration and ICAM-1 expression&#44; remained unchanged in the BD animals despite TEB&#46; Moreover&#44; the serum levels of cytokines and corticosterone did not change after the treatment of BD rats with TEB&#46;</p><p id="para230" class="elsevierStylePara elsevierViewall">Hemodynamic instability is a major challenge in the treatment of BD donors because it leads to the impairment of organ perfusion and compromises the viability of these organs for transplantation&#46; Although hypertension may occur during the phase of cerebral herniation&#44; hypotension affects almost all patients after BD <a class="elsevierStyleCrossRef" href="#bib18">18</a>&#46; Indeed&#44; in animal models&#44; the hypotensive event that accompanies BD is initiated by both rapid and slow augmentation of intracranial pressure <a class="elsevierStyleCrossRef" href="#bib10">10</a>&#44;<a class="elsevierStyleCrossRef" href="#bib19">19</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib21">21</a>&#46; Nevertheless&#44; the important question of how the modification of sympathetic activity after BD impacts microcirculation behavior and hypoperfusion in different organs remains unanswered&#46;</p><p id="para240" class="elsevierStylePara elsevierViewall">In this study&#44; we observed the hemodynamic&#44; microcirculatory&#44; and inflammatory effects of TEB performed immediately before BD induction in rats that did not receive any drugs for blood pressure maintenance&#46; Thus&#44; our non-treated rats are similar to marginal donors in clinical practice&#46; The chemical sympathectomy produced by TEB using bupivacaine prevented the hypertensive event associated with BD&#44; although a slight increase in mean arterial pressure was observed when the balloon was inflated&#46; Furthermore&#44; we demonstrated for the first time that mesenteric hypoperfusion is not affected by the inhibition of the hypertensive episode&#46; The long episode of hypotension that generally starts immediately after the hypertensive peak was not affected by TEB&#46; This event was associated with rapid and persistent hypoperfusion of the mesenteric microcirculation&#46; Such hypoperfusion was previously demonstrated by our group in the mesentery <a class="elsevierStyleCrossRef" href="#bib8">8</a> and by others in the pancreas and the liver <a class="elsevierStyleCrossRef" href="#bib15">15</a>&#44;<a class="elsevierStyleCrossRef" href="#bib16">16</a>&#46; Additional real-time monitoring of the mesenteric microcirculation during the first 30 min after BD induction confirmed that mesenteric hypoperfusion occurs immediately after BD and concomitantly with the onset of the sustained hypotensive episode &#40;unpublished data&#41;&#46; This observation suggests that microcirculatory abnormalities can occur independently of an increase in arterial pressure&#44; suggesting the involvement of other mechanisms triggered by BD in these microcirculatory abnormalities&#46;</p><p id="para250" class="elsevierStylePara elsevierViewall">It has been demonstrated that BD leads to a decrease in organ perfusion and a progressive activation of endothelial cells and leukocytes <a class="elsevierStyleCrossRef" href="#bib8">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib22">22</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib25">25</a>&#46; It is known that BD triggers a series of inflammatory effects&#44; including increased expression of adhesion molecules&#44; leukocyte transmigration to the perivascular tissue in various organs&#44; and increased serum levels of cytokines <a class="elsevierStyleCrossRef" href="#bib2">2</a>&#44;<a class="elsevierStyleCrossRef" href="#bib3">3</a>&#44;<a class="elsevierStyleCrossRef" href="#bib26">26</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib28">28</a>&#46; The present data indicate that the inflammation in the mesenteric microcirculation is not affected by TEB&#46; The animals in both BD groups exhibited similar numbers of rolling&#44; adherent&#44; and migrating leukocytes&#44; as well as comparably increased levels of ICAM-1 expression in endothelial cells&#59; these characteristics were associated with a pronounced reduction in the serum corticosterone levels&#46; It is known that BD impairs the endocrine system and decreases the release of hormones such as triiodothyronine&#44; thyroxin&#44; cortisol&#44; and anti-diuretic hormone&#44; suggesting an interruption along the hypothalamic-pituitary-adrenal axis <a class="elsevierStyleCrossRef" href="#bib29">29</a>&#44;<a class="elsevierStyleCrossRef" href="#bib30">30</a>&#46; In this regard&#44; it has been shown that in healthy subjects&#44; endogenous glucocorticoids that are secreted in large amounts at the early stages of an inflammatory reaction regulate the functions of almost all cellular components of the microcirculation <a class="elsevierStyleCrossRef" href="#bib31">31</a>&#46; Indeed&#44; the SH rats exhibited increased levels of corticosterone in association with reduced ICAM-1 expression compared to the BD rats&#46; Furthermore&#44; the serum levels of cytokines were similar between the groups&#44; suggesting that the release of cytokines triggered by BD-associated trauma <a class="elsevierStyleCrossRef" href="#bib8">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib28">28</a> was not affected by TEB&#46;</p><p id="para260" class="elsevierStylePara elsevierViewall">It has been well documented that abnormalities in microcirculatory perfusion&#44; including decreased vascular density&#44; especially in the small vessels&#44; and a large number of non-perfused and intermittently perfused small vessels&#44; which occur in septic patients&#44; are not affected by the global hemodynamic state or the use of adrenergic agents <a class="elsevierStyleCrossRef" href="#bib32">32</a>&#44;<a class="elsevierStyleCrossRef" href="#bib33">33</a>&#46; The experimental findings are consistent with the clinical evidence that sepsis induces microvascular changes that may play an important role in the development of organ dysfunction <a class="elsevierStyleCrossRef" href="#bib32">32</a>&#44;<a class="elsevierStyleCrossRef" href="#bib34">34</a>&#44;<a class="elsevierStyleCrossRef" href="#bib35">35</a>&#46; These results justify the attempts to revert these alterations&#46; Alternatively&#44; microcirculatory targets are not currently considered for optimizing the therapy after BD&#46; Fluid replacement&#44; the use of vasoactive drugs&#44; and hormone replacement therapy are the strategies used to achieve hemodynamic stability and to maintain organ function in potential BD organ donors <a class="elsevierStyleCrossRef" href="#bib18">18</a>&#46; Although these interventions may influence the microcirculation&#44; management aimed at stabilizing the global hemodynamic state does not always ensure the normalization of tissue perfusion&#44; which is an important objective in shock states of various etiologies&#46;</p><p id="para270" class="elsevierStylePara elsevierViewall">In conclusion&#44; the results of this study indicate that epidural anesthesia with bupivacaine does not affect the sustained hypoperfusion and inflammation in the mesenteric microvessels induced by BD&#44; suggesting that microcirculatory abnormalities can occur independently of changes in mean arterial pressure&#46; These findings clearly demonstrate that therapies aimed at maintaining the microcirculation may effectively compensate for the perfusion abnormalities after BD&#44; thereby potentially improving the quality of donor organs for transplantation&#46;</p></span><span id="cesec150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle200">AUTHOR CONTRIBUTIONS</span><p id="para280" class="elsevierStylePara elsevierViewall">Simas R participated in the research design&#44; performance of the research&#44; the data analysis&#44; and the writing of the paper&#46; Ferreira SG&#44; Menegat L&#44; Zanoni FL&#44; and Correia CJ participated in the performance of the research&#46; Silva IA participated in the research design and the writing of the paper&#46; Sannomiya P and Moreira LF participated in the research design&#44; the data analysis&#44; and the writing of the paper&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:8 [
        0 => array:2 [
          "identificador" => "xpalclavsec1582340"
          "titulo" => "KEYWORDS"
        ]
        1 => array:2 [
          "identificador" => "cesec10"
          "titulo" => "INTRODUCTION"
        ]
        2 => array:3 [
          "identificador" => "cesec20"
          "titulo" => "MATERIAL AND METHODS"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "cesec30"
              "titulo" => "Brain death model and thoracic epidural anesthesia"
            ]
            1 => array:2 [
              "identificador" => "cesec40"
              "titulo" => "Blood gas&#44; electrolyte&#44; and lactate measurements and white blood cell counts"
            ]
            2 => array:2 [
              "identificador" => "cesec50"
              "titulo" => "Intravital microscopy of the mesenteric microcirculation"
            ]
            3 => array:2 [
              "identificador" => "cesec60"
              "titulo" => "Evaluation of intercellular adhesion molecule 1 expression via immunohistochemistry"
            ]
            4 => array:2 [
              "identificador" => "cesec70"
              "titulo" => "Serum concentrations of cytokines and corticosterone"
            ]
            5 => array:2 [
              "identificador" => "cesec80"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        3 => array:3 [
          "identificador" => "cesec90"
          "titulo" => "RESULTS"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "cesec100"
              "titulo" => "Hemodynamic parameters"
            ]
            1 => array:2 [
              "identificador" => "cesec110"
              "titulo" => "Mesenteric microcirculation parameters"
            ]
            2 => array:2 [
              "identificador" => "cesec120"
              "titulo" => "Expression of mesenteric intercellular adhesion molecule 1 and the serum corticosterone levels"
            ]
            3 => array:2 [
              "identificador" => "cesec130"
              "titulo" => "Serum cytokine levels"
            ]
          ]
        ]
        4 => array:2 [
          "identificador" => "cesec140"
          "titulo" => "DISCUSSION"
        ]
        5 => array:2 [
          "identificador" => "cesec150"
          "titulo" => "AUTHOR CONTRIBUTIONS"
        ]
        6 => array:2 [
          "identificador" => "xack639282"
          "titulo" => "ACKNOWLEDGMENTS"
        ]
        7 => array:1 [
          "titulo" => "REFERENCES"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2015-02-10"
    "fechaAceptado" => "2015-03-31"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "KEYWORDS"
          "identificador" => "xpalclavsec1582340"
          "palabras" => array:4 [
            0 => "Brain Death"
            1 => "Autonomic Storm"
            2 => "Microcirculation"
            3 => "Intravital Microscopy"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVES&#58;</span><p id="spara60" class="elsevierStyleSimplePara elsevierViewall">Brain death is typically followed by autonomic changes that lead to hemodynamic instability&#44; which is likely associated with microcirculatory dysfunction and inflammation&#46; We evaluated the role of the microcirculation in the hemodynamic and inflammatory events that occur after brain death and the effects of autonomic storm inhibition via thoracic epidural blockade on mesenteric microcirculatory changes and inflammatory responses&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS&#58;</span><p id="spara70" class="elsevierStyleSimplePara elsevierViewall">Male Wistar rats were anesthetized and mechanically ventilated&#46; Brain death was induced via intracranial balloon inflation&#46; Bupivacaine &#40;brain death-thoracic epidural blockade group&#41; or saline &#40;brain death group&#41; infusion via an epidural catheter was initiated immediately before brain death induction&#46; Sham-operated animals were used as controls &#40;SH group&#41;&#46; The mesenteric microcirculation was analyzed via intravital microscopy&#44; and the expression of adhesion molecules was evaluated via immunohistochemistry 180 min after brain death induction&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS&#58;</span><p id="spara80" class="elsevierStyleSimplePara elsevierViewall">A significant difference in mean arterial pressure behavior was observed between the brain death-thoracic epidural blockade group and the other groups&#44; indicating that the former group experienced autonomic storm inhibition&#46; However&#44; the proportion of perfused small vessels in the brain death-thoracic epidural blockade group was similar to or lower than that in the brain death and SH groups&#44; respectively&#46; The expression of intercellular adhesion molecule 1 was similar between the brain death-thoracic epidural blockade and brain death groups but was significantly lower in the SH group than in the other two groups&#46; The number of migrating leukocytes in the perivascular tissue followed the same trend for all groups&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSIONS&#58;</span><p id="spara90" class="elsevierStyleSimplePara elsevierViewall">Although thoracic epidural blockade effectively inhibited the autonomic storm&#44; it did not affect mesenteric hypoperfusion or inflammation induced by brain death&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "ceabs10"
            "titulo" => "OBJECTIVES&#58;"
          ]
          1 => array:2 [
            "identificador" => "ceabs20"
            "titulo" => "METHODS&#58;"
          ]
          2 => array:2 [
            "identificador" => "ceabs30"
            "titulo" => "RESULTS&#58;"
          ]
          3 => array:2 [
            "identificador" => "ceabs40"
            "titulo" => "CONCLUSIONS&#58;"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:1 [
        "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">No potential conflict of interest was reported&#46;</p>"
      ]
    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "fig1"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 423
            "Ancho" => 788
            "Tamanyo" => 37211
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Mean arterial pressure of sham-operated rats &#40;SH&#41;&#44; brain-dead non-treated rats &#40;BD&#41;&#44; and brain-dead rats under thoracic epidural blockade &#40;BD-TEB&#41; 180 minutes after the surgical procedures&#46; The animals were monitored over time&#46; The data are presented as the means&#177;SEM&#59; ANOVA p&#60;0&#46;001&#59; &#42;<span class="elsevierStyleItalic">p</span>&#60;0&#46;05 vs&#46; the other groups&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig2"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 640
            "Ancho" => 788
            "Tamanyo" => 145231
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Intravital microscopy of the rat mesenteric microcirculation&#46; A&#44; The percentages of perfused small vessels &#40;&#60;30 &#956;m&#41; in sham-operated rats &#40;SH&#41;&#44; brain-dead non-treated rats &#40;BD&#41;&#44; and brain-dead rats under thoracic epidural blockade &#40;BD-TEB&#41; 180 min after the surgical procedures&#46; The data are presented as the means&#177;SEM&#59; p ANOVA&#61;0&#46;002&#59; &#42;<span class="elsevierStyleItalic">p</span>&#60;0&#46;05 vs&#46; the other groups&#46; B&#44; C&#44; and D&#44; Photomicrographs of mesenteric microvessels in the SH&#44; BD&#44; and BD-TEB groups&#44; respectively&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig3"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 282
            "Ancho" => 789
            "Tamanyo" => 28474
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Expression of intercellular adhesion molecule &#40;ICAM&#41;-1 on mesenteric endothelial cells &#40;p ANOVA &#60;0&#46;001&#41; and the serum levels of corticosterone &#40;p ANOVA&#61;0&#46;01&#41; in sham-operated rats &#40;SH&#41;&#44; brain-dead non-treated rats &#40;BD&#41;&#44; and brain-dead rats under thoracic epidural blockade &#40;BD-TEB&#41; 180 min after the surgical procedures&#46; The data are presented as the means&#177;SEM&#46; &#42;<span class="elsevierStyleItalic">p</span>&#60;0&#46;05 vs&#46; the other groups&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl1"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="tfn1" class="elsevierStyleSimplePara elsevierViewall">Rollers&#58; leukocytes&#47;5 min&#59; Adhered&#58; leukocytes&#47;100 &#181;m venule length&#59; Migrated&#58; leukocytes&#47;5&#44;000 &#181;m<span class="elsevierStyleSup">2</span>&#59; WBC&#58; White blood cells&#47;mm<span class="elsevierStyleSup">3</span>&#46; SH&#58; sham-operated rats&#59; BD&#58; brain-dead non-treated rats&#59; BD-TEB&#58; brain-dead rats under thoracic epidural blockade&#46; These measurements were performed 180 min after the surgical procedures&#46; The data are presented as the means&#177;SEM&#46; &#42;<span class="elsevierStyleItalic">p</span>&#60;0&#46;01 vs&#46; the other groups&#46; &#42;&#42;<span class="elsevierStyleItalic">p</span>&#60;0&#46;05 vs&#46; the other groups&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">SH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">BD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">BD-TEB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col"><span class="elsevierStyleItalic">p</span> ANOVA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Rollers</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">165 &#40;12&#41;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">44 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">31 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Adherent</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">6&#46;9 &#40;0&#46;6&#41;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">4&#46;5 &#40;0&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">3&#46;2 &#40;0&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Migrated</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">1&#46;3 &#40;0&#46;2&#41;&#42;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">2&#46;5 &#40;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">1&#46;8 &#40;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">WBC</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">11&#44;771 &#40;1&#44;122&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">10&#44;450 &#40;2&#44;109&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">8&#44;667 &#40;1&#44;196&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="middle">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">The results of the evaluation of the rat mesenteric microcirculation via intravital microscopy&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl2"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="tfn2" class="elsevierStyleSimplePara elsevierViewall">SH&#58; sham-operated rats&#59; BD&#58; brain-dead non-treated rats&#59; BD-TEB&#58; brain-dead rats under thoracic epidural blockade&#46; These measurements were performed 180 min after the surgical procedures&#46; The data are presented as the means&#177;SEM&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">TNF-&#945; &#40;pg&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">IL-1&#946; &#40;pg&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">IL-6 &#40;pg&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">IL-10 &#40;pg&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">SH</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;066&#177;0&#46;005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;102&#177;0&#46;017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;131&#177;0&#46;022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;112&#177;0&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">BD</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;054&#177;0&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;074&#177;0&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;130&#177;0&#46;043&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;089&#177;0&#46;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">BD-TEB</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;067&#177;0&#46;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;090&#177;0&#46;017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;151&#177;0&#46;043&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;096&#177;0&#46;010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">p</span> ANOVA</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara50" class="elsevierStyleSimplePara elsevierViewall">The results of the evaluation of the serum cytokine levels via enzyme-linked immunosorbent assays&#46;</p>"
        ]
      ]
      5 => array:5 [
        "identificador" => "fig4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 272
            "Ancho" => 780
            "Tamanyo" => 52620
          ]
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec10"
          "bibliografiaReferencia" => array:35 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Endocrine changes and metabolic responses in a validated canine brain death model"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              HB Bittner \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              SW Kendall \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              EP Chen \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              P Van Trigt \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/0883-9441(95)90017-9"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Crit Care"
                        "fecha" => "1995"
                        "volumen" => "10"
                        "numero" => "2"
                        "paginaInicial" => "56"
                        "paginaFinal" => "63"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7647843"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/0883-9441(95)90017-9"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;0883-9441&#40;95&#41;90017-9"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systemic inflammation in the brain-dead organ donor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              A Barklin \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1399-6576.2008.01879.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Acta Anaesthesiol Scand"
                        "fecha" => "2009"
                        "volumen" => "53"
                        "numero" => "4"
                        "paginaInicial" => "425"
                        "paginaFinal" => "435"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19226294"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1111/j.1399-6576.2008.01879.x"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1111&#47;aas&#46;2009&#46;53&#46;issue-4"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib3"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brain death&#58; repercussion on the organs and tissues"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              JM Dom&#237;nguez-Rold&#225;n \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              C Garc&#237;a-Alfaro \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              PI Jimen&#233;z-Gonz&#225;lez \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              F Hern&#225;ndez-Haza&#241;as \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              ML Gasc&#243;n Castillo \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              JJ Egea Guerrero \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/j.medin.2009.03.008"
                      "Revista" => array:7 [
                        "tituloSerie" => "Med Intensiva"
                        "fecha" => "2009"
                        "volumen" => "33"
                        "numero" => "9"
                        "paginaInicial" => "434"
                        "paginaFinal" => "441"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19922825"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/j.medin.2009.03.008"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;medin&#46;2009&#46;03&#46;008"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib4"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Improvement of donor myocardial function after treatment of autonomic storm during brain death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              G Audibert \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              C Charpentier \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              C Seguin-Devaux \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              PA Charretier \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              H Gr&#233;goire \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              Y Devaux \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1097/01.tp.0000235825.97538.d5"
                      "Revista" => array:7 [
                        "tituloSerie" => "Transplantation"
                        "fecha" => "2006"
                        "volumen" => "82"
                        "numero" => "8"
                        "paginaInicial" => "1031"
                        "paginaFinal" => "1036"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17060850"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1097/01.tp.0000235825.97538.d5"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1097&#47;01&#46;tp&#46;0000235825&#46;97538&#46;d5"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              B Shivalkar \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Van Loon \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              W Wieland \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              TB Tjandra-Maga \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              M Borgers \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              C Plets \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1161/01.cir.87.1.230"
                      "Revista" => array:7 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "1993"
                        "volumen" => "87"
                        "numero" => "1"
                        "paginaInicial" => "230"
                        "paginaFinal" => "239"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8419012"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1161/01.cir.87.1.230"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1161&#47;01&#46;CIR&#46;87&#46;1&#46;230"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Activation of proinflammatory mediators in heart transplants from brain-dead donors&#58; evidence from a model of chronic rat cardiac allograft rejection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              MJ Wilhelm \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Pratschke \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              F Beato \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              M Taal \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              IA Laskowski \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              DM Paz \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/s0041-1345(02)03283-9"
                      "Revista" => array:7 [
                        "tituloSerie" => "Transplant Proc"
                        "fecha" => "2002"
                        "volumen" => "34"
                        "numero" => "6"
                        "paginaInicial" => "2359"
                        "paginaFinal" => "2360"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12270436"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/s0041-1345(02)03283-9"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;S0041-1345&#40;02&#41;03283-9"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of brain death on organ quality and transplant outcome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              B Floerchinger \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              R Oberhuber \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              SG Tullius \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.trre.2011.10.001"
                      "Revista" => array:7 [
                        "tituloSerie" => "Transplant Rev &#40;Orlando&#41;"
                        "fecha" => "2012"
                        "volumen" => "26"
                        "numero" => "2"
                        "paginaInicial" => "54"
                        "paginaFinal" => "59"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22459036"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation&#58; an intravital microscopic study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              R Simas \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              P Sannomiya \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JW Cruz \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              J Correia Cde \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              FL Zanoni \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              M Kase \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.6061/clinics/2012(sup01)13"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clinics"
                        "fecha" => "2012"
                        "volumen" => "67"
                        "numero" => "1"
                        "paginaInicial" => "69"
                        "paginaFinal" => "75"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22584709"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.6061/clinics/2012(sup01)13"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;6061&#47;clinics"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhibition of autonomic storm by epidural anesthesia does not influence cardiac inflammatory response after brain death in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              IA Silva \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              CJ Correia \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              R Simas \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              JW Cruz \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              SG Ferreira \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              FL Zanoni \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/j.transproceed.2012.07.108"
                      "Revista" => array:7 [
                        "tituloSerie" => "Transplant Proc"
                        "fecha" => "2012"
                        "volumen" => "44"
                        "numero" => "7"
                        "paginaInicial" => "2213"
                        "paginaFinal" => "2218"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22974957"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/j.transproceed.2012.07.108"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;transproceed&#46;2012&#46;07&#46;108"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluating lung injury at increasing time intervals in a murine brain death model"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              S Wauters \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Somers \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              S De Vleeschauwer \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              E Verbeken \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              GM Verleden \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              J van Loon \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jss.2013.01.011"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Surg Res"
                        "fecha" => "2013"
                        "volumen" => "183"
                        "numero" => "1"
                        "paginaInicial" => "419"
                        "paginaFinal" => "426"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23394934"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/j.jss.2013.01.011"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;jss&#46;2013&#46;01&#46;011"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protective effects of labetalol on myocardial contractile function in brain-dead pigs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              EM Siaghy \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              P Halejcio-Delophont \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              Y Devaux \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              JP Richoux \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              JP Villemot \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              C Burlet \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/s0041-1345(98)00833-1"
                      "Revista" => array:7 [
                        "tituloSerie" => "Transplant Proc"
                        "fecha" => "1998"
                        "volumen" => "30"
                        "numero" => "6"
                        "paginaInicial" => "2842"
                        "paginaFinal" => "2843"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9745589"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/s0041-1345(98)00833-1"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;S0041-1345&#40;98&#41;00833-1"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Experimental treatment with beta blockers of hemodynamic and myocardial changes in organ donors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              R Ojeda-Rivero \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Hern&#225;ndez-Fern&#225;ndez \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JM Dominguez-Rold&#225;n \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              E Calder&#243;n \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              M Ruiz \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              E Lage \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/s0041-1345(01)02720-8"
                      "Revista" => array:7 [
                        "tituloSerie" => "Transplant Proc"
                        "fecha" => "2002"
                        "volumen" => "34"
                        "numero" => "1"
                        "paginaInicial" => "185"
                        "paginaFinal" => "186"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11959241"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/s0041-1345(01)02720-8"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;S0041-1345&#40;01&#41;02720-8"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Central sympathetic blockade ameliorates brain death-induced cardiotoxicity and associated changes in myocardial gene expression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              T Yeh Jr \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              AS Wechsler \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              L Graham \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              KE Loesser \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              DA Sica \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              L Wolfe \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1067/mtc.2002.124887"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Thorac Cardiovasc Surg"
                        "fecha" => "2002"
                        "volumen" => "124"
                        "numero" => "6"
                        "paginaInicial" => "1087"
                        "paginaFinal" => "1098"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12447173"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1067/mtc.2002.124887"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1067&#47;mtc&#46;2002&#46;124887"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevention of myocardial injury during brain death by total cardiac sympathectomy in the Chacma baboon"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              D Novitzky \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              WN Wicomb \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              DK Cooper \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              AG Rose \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              B Reichart \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/s0003-4975(10)63032-9"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Thorac Surg"
                        "fecha" => "1986"
                        "volumen" => "41"
                        "numero" => "5"
                        "paginaInicial" => "520"
                        "paginaFinal" => "524"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3707246"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/s0003-4975(10)63032-9"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;S0003-4975&#40;10&#41;63032-9"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brain death impairs pancreatic microcirculation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              R Obermaier \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              E von Dobschuetz \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              T Keck \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              HH Hopp \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              O Drognitz \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              W Schareck \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1046/j.1600-6143.2003.00317.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Transplant"
                        "fecha" => "2004"
                        "volumen" => "4"
                        "numero" => "2"
                        "paginaInicial" => "210"
                        "paginaFinal" => "215"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14974941"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1046/j.1600-6143.2003.00317.x"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1046&#47;j&#46;1600-6143&#46;2003&#46;00317&#46;x"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Synergistic effects of brain death and liver steatosis on the hepatic microcirculation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              K Yamagami \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Hutter \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              Y Yamamoto \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              RJ Schauer \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              G Enders \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              R Leiderer \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1097/01.tp.0000167723.46580.78"
                      "Revista" => array:7 [
                        "tituloSerie" => "Transplantation"
                        "fecha" => "2005"
                        "volumen" => "80"
                        "numero" => "4"
                        "paginaInicial" => "500"
                        "paginaFinal" => "505"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16123725"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1097/01.tp.0000167723.46580.78"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1097&#47;01&#46;tp&#46;0000167723&#46;46580&#46;78"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Influence of brain death and associated trauma on solid organ histological characteristics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              R Simas \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              DH Kogiso \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              CJ Correia \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              LF Silva \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              IA Silva \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              JW Cruz \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1590/s0102-86502012000700006"
                      "Revista" => array:7 [
                        "tituloSerie" => "Acta Cir Bras"
                        "fecha" => "2012"
                        "volumen" => "27"
                        "numero" => "7"
                        "paginaInicial" => "465"
                        "paginaFinal" => "470"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22760831"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1590/s0102-86502012000700006"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1590&#47;S0102-86502012000700006"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Critical care management of potential organ donors&#58; our current standard"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              C Dictus \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              B Vienenkoetter \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Esmaeilzadeh \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              A Unterberg \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              R Ahmadi \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1399-0012.2009.01102.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Transplant"
                        "fecha" => "2009"
                        "volumen" => "23"
                        "numero" => "Suppl 21"
                        "paginaInicial" => "2"
                        "paginaFinal" => "9"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19930309"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1111/j.1399-0012.2009.01102.x"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1111&#47;ctr&#46;2009&#46;23&#46;issue-s21"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Graft-specific immune cells communicate inflammatory immune responses after brain death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              B Floerchinger \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              X Ge \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              YL Lee \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              A Jurisch \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              RF Padera \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              C Schmid \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/j.healun.2012.09.005"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Heart Lung Transplant"
                        "fecha" => "2012"
                        "volumen" => "31"
                        "numero" => "12"
                        "paginaInicial" => "1293"
                        "paginaFinal" => "1300"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23102910"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/j.healun.2012.09.005"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;healun&#46;2012&#46;09&#46;005"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brain death induced by cerebral haemorrhage - a new porcine model evaluated by CT angiography"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              CL Hvas \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              TK Nielsen \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Barklin \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              JC S&#8856;rensen \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              M Pedersen \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              G Andersen \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1399-6576.2012.02682.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Acta Anaesthesiol Scand"
                        "fecha" => "2012"
                        "volumen" => "56"
                        "numero" => "8"
                        "paginaInicial" => "995"
                        "paginaFinal" => "1005"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22409633"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1111/j.1399-6576.2012.02682.x"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1111&#47;aas&#46;2012&#46;56&#46;issue-8"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacological normalization of circulation after acute brain death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              S Steen \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              T Sj&#246;berg \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              Q Liao \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              G Bozovic \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              B Wohlfart \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1399-6576.2012.02721.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Acta Anaesthesiol Scand"
                        "fecha" => "2012"
                        "volumen" => "56"
                        "numero" => "8"
                        "paginaInicial" => "1006"
                        "paginaFinal" => "1012"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22651688"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1111/j.1399-6576.2012.02721.x"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1111&#47;aas&#46;2012&#46;56&#46;issue-8"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of brain death and hemodynamic status on function and immunologic activation of the potential donor liver in the rat"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              JA van Der Hoeven \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              GJ Ter Horst \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              G Molema \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              P de Vos \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              AR Girbes \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              F Postema \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1097/00000658-200012000-00009"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Surg"
                        "fecha" => "2000"
                        "volumen" => "232"
                        "numero" => "6"
                        "paginaInicial" => "804"
                        "paginaFinal" => "813"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11088075"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1097/00000658-200012000-00009"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1097&#47;00000658-200012000-00009"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protective effects of urinary trypsin inhibitor &#40;UTI&#41; on hepatic microvasculature in hypotensive brain-dead rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              K Itabashi \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              Y Ito \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              T Takahashi \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              K Ishii \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              K Sato \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              A Kakita \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1159/000063074"
                      "Revista" => array:7 [
                        "tituloSerie" => "Eur Surg Res"
                        "fecha" => "2002"
                        "volumen" => "34"
                        "numero" => "4"
                        "paginaInicial" => "330"
                        "paginaFinal" => "338"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12145560"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1159/000063074"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1159&#47;000063074"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relationship between duration of brain death and hemodynamic &#40;in&#41;stability on progressive dysfunction and increased immunologic activation of donor kidneys"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              JA van der Hoeven \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              G Molema \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              GJ Ter Horst \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              RL Freund \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              J Wiersema \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              R van Schilfgaarde \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1046/j.1523-1755.2003.00272.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2003"
                        "volumen" => "64"
                        "numero" => "5"
                        "paginaInicial" => "1874"
                        "paginaFinal" => "1882"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14531823"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1046/j.1523-1755.2003.00272.x"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1046&#47;j&#46;1523-1755&#46;2003&#46;00272&#46;x"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Carbon monoxide inhalation ameliorates conditions of lung grafts from rat brain death donors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              HC Zhou \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              WG Ding \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              XG Cui \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              P Pan \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              B Zhang \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              WZ Li \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Chin Med J &#40;Engl&#41;"
                        "fecha" => "2008"
                        "volumen" => "121"
                        "numero" => "15"
                        "paginaInicial" => "1411"
                        "paginaFinal" => "1419"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18959119"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detrimental consequences of brain injury on peripheral cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              A Catania \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              C Lonati \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              A Sordi \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              S Gatti \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbi.2009.04.006"
                      "Revista" => array:7 [
                        "tituloSerie" => "Brain Behav Immun"
                        "fecha" => "2009"
                        "volumen" => "23"
                        "numero" => "7"
                        "paginaInicial" => "877"
                        "paginaFinal" => "884"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19394418"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/j.bbi.2009.04.006"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;bbi&#46;2009&#46;04&#46;006"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib27"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brain death induces inflammation in the donor intestine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              LG Koudstaal \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              NA &#8216;t Hart \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              PJ Ottens \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              A van den Berg \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              RJ Ploeg \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              H van Goor \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1097/TP.0b013e31817ba53a"
                      "Revista" => array:7 [
                        "tituloSerie" => "Transplantation"
                        "fecha" => "2008"
                        "volumen" => "86"
                        "numero" => "1"
                        "paginaInicial" => "148"
                        "paginaFinal" => "154"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18622292"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1097/TP.0b013e31817ba53a"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1097&#47;TP&#46;0b013e31817ba53a"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib28"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Time-dependent changes in donor brain death related processes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              TA Schuurs \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              AM Morariu \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              PJ Ottens \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              NA &#8216;t Hart \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              SH Popma \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              HG Leuvenink \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1600-6143.2006.01547.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Transplant"
                        "fecha" => "2006"
                        "volumen" => "6"
                        "numero" => "12"
                        "paginaInicial" => "2903"
                        "paginaFinal" => "2911"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17062004"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1111/j.1600-6143.2006.01547.x"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1111&#47;ajt&#46;2006&#46;6&#46;issue-12"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib29"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brain death and its influence on donor organ quality and outcome after transplantation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              J Pratschke \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              MJ Wilhelm \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              M Kusaka \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              M Basker \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              DK Cooper \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              WW Hancock \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1097/00007890-199902150-00001"
                      "Revista" => array:7 [
                        "tituloSerie" => "Transplantation"
                        "fecha" => "1999"
                        "volumen" => "67"
                        "numero" => "3"
                        "paginaInicial" => "343"
                        "paginaFinal" => "348"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10030276"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1097/00007890-199902150-00001"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1097&#47;00007890-199902150-00001"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib30"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brain death and its impact on the donor heart-lessons from animal models"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              MJ Wilhelm \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Pratschke \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              IA Laskowski \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              DM Paz \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              NL Tilney \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1016/s1053-2498(00)00073-5"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Heart Lung Transplant"
                        "fecha" => "2000"
                        "volumen" => "19"
                        "numero" => "5"
                        "paginaInicial" => "414"
                        "paginaFinal" => "418"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10808147"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1016/s1053-2498(00)00073-5"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;S1053-2498&#40;00&#41;00073-5"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib31"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The microcirculation and inflammation&#58; site of action for glucocorticoids"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              M Perretti \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Ahluwalia \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Microcirculation"
                        "fecha" => "2000"
                        "volumen" => "7"
                        "numero" => "3"
                        "paginaInicial" => "147"
                        "paginaFinal" => "161"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1111&#47;micc&#46;2000&#46;7&#46;issue-3"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib32"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Microvascular blood flow is altered in patients with sepsis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              D De Backer \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              J Creteur \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              JC Preiser \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              MJ Dubois \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              JL Vincent \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200109-016oc"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2002"
                        "volumen" => "166"
                        "numero" => "1"
                        "paginaInicial" => "98"
                        "paginaFinal" => "104"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12091178"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1164/rccm.200109-016oc"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1164&#47;rccm&#46;200109-016OC"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib33"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Microcirculatory alterations&#58; potential mechanisms and implications for therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              D De Backer \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              K Donadello \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              FS Taccone \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              G Ospina-Tascon \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              D Salgado \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              JL Vincent \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1186/2110-5820-1-27"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intensive Care"
                        "fecha" => "2011"
                        "volumen" => "1"
                        "numero" => "1"
                        "paginaInicial" => "27"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21906380"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1186/2110-5820-1-27"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1186&#47;2110-5820-1-27"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib34"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Decreased capillary density in&#63;vivo in bowel mucosa of rats with normotensive sepsis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              I Farquhar \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              CM Martin \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              C Lam \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              R Potter \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              CG Ellis \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              WJ Sibbald \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1006/jsre.1996.0103"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Surg Res"
                        "fecha" => "1996"
                        "volumen" => "61"
                        "numero" => "1"
                        "paginaInicial" => "190"
                        "paginaFinal" => "196"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8769965"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1006/jsre.1996.0103"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1006&#47;jsre&#46;1996&#46;0103"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib35"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              Y Sakr \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              MJ Dubois \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              D De Backer \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              J Creteur \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              JL Vincent \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1097/01.ccm.0000138558.16257.3f"
                      "Revista" => array:7 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2004"
                        "volumen" => "32"
                        "numero" => "9"
                        "paginaInicial" => "1825"
                        "paginaFinal" => "1831"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15343008"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1097/01.ccm.0000138558.16257.3f"
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1097&#47;01&#46;CCM&#46;0000138558&#46;16257&#46;3F"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack639282"
        "titulo" => "ACKNOWLEDGMENTS"
        "texto" => "<p id="para290" class="elsevierStylePara elsevierViewall">This research was supported by Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo &#40;FAPESP&#41;&#44; Grant number 09&#47;10759-9&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/18075932/0000007000000006/v1_202212011416/S1807593222013758/v1_202212011416/en/main.assets"
  "Apartado" => null
  "PDF" => "https://static.elsevier.es/multimedia/18075932/0000007000000006/v1_202212011416/S1807593222013758/v1_202212011416/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222013758?idApp=UINPBA00004N"
]

Article information

ISSN: 18075932
Original language: English

DOI:10.6061/clinics/2015(06)11

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	4	1	5
2024 October	45	28	73
2024 September	39	14	53
2024 August	35	16	51
2024 July	30	22	52
2024 June	37	11	48
2024 May	27	11	38
2024 April	44	9	53
2024 March	46	11	57
2024 February	30	10	40
2024 January	31	10	41
2023 December	14	13	27
2023 November	18	18	36
2023 October	23	20	43
2023 September	15	12	27
2023 August	11	2	13
2023 July	5	8	13
2023 June	11	5	16
2023 May	29	0	29
2023 April	8	1	9
2023 March	3	3	6
2023 February	0	2	2
2023 January	8	2	10
2022 December	15	5	20

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter