La utilidad de la relación presión arterial pulmonar - índice cardiaco para identificar respondedores hemodinámicos a la administración aguda de oxígeno en sujetos con enfermedad pulmonar obstructiva crónica e hipertensión pulmonar

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Instituto Nacional de Cardiología Ignacio Chávez, México. " "etiqueta" => "a" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Cardiopulmonary Department. Instituto Nacional de Cardiología Ignacio Chávez, México. " "etiqueta" => "b" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Clinical Cardiology Department. Instituto Nacional de Cardiología Ignacio Chávez, México. " "etiqueta" => "c" "identificador" => "affc" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "The role of pulmonary pressure/cardiac index to identify pulmonary hemodynamic responders to acute oxygen breathing pulmonary hypertension COPD patients" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "293v81n03-90028657fig3.jpg" "Alto" => 812 "Ancho" => 1025 "Tamanyo" => 123172 ] ] "descripcion" => array:1 [ "en" => "0028657fig3.jpg" width="1025" height="812" alt="Table 3. mPAP/CI and Pext results breath" ] ] ] "textoCompleto" => "IntroductionDue to the meaningless significance of calculated pulmonary vascular resistance (PVR),1 a bedside approach to get a deeper insight into the PVR linear component nature is based on the determination of multipoint mean pulmonary artery pressure (mPAP) - cardiac index (CI) - relationship.2-5 In most cardiac/pulmonary diseases mPAP/CI are well described by a linear approximation, but their extrapolation to the pressure axis at zero flow (Pext) may be higher than pulmonary artery occluded pressure or left atrial pressure.1,2,5 An increased Pext could be explained by an increased mean closing pressure in small arterioles or capillaries (or both), or also could result from the forces on the outside of the vessels, such as abnormal alveolar pressure on the pulmonary capillaries.6-11 Approach for PVR determination, that from time to time had been attempted in cohorts composed by few cases with pulmonary hypertension (PH) due to lung diseases in the last 40 years. Although, to our knowledge this hemodynamic approach has not been attempted to evaluate the acute role of oxygen according to mPAP level in PH chronic obstructive pulmonary disease (COPD) patients.3-5 Information that could be important, since it has been suggested that when resting mPAP is moderately to markedly elevated (>30 mmHg) at the onset of long-term oxygen therapy (LTOT), the survival rate is decreased in comparison with patients with no or mild PH (<30 mmHg).12-17 Accordingly, it has been proposed that LTOT should be started earlier at the stage of mild (or even absent) PH to favor the long-term survival in hypoxemic COPD patients.15ObjectiveTo extend the limited clinical information in relation to multipoint mPAP/CI in PH-COPD; second, if mPAP/CI location, the slope value and Pext analysis could help to better identify pulmonary vasomotion due to acute oxygen breathing and in consequence recognize which cases could be hemodynamically beneficiated by decreasing right ventricular (RV) afterload among PH-COPD patients. MethodsPatients. The protocol was approved by the ethics review commission. The series of studied patients (n = 40; born, raised and permanent residents of Mexico City (altitude 2240 meters)) were selected from a group of 677 cases, which represented the total number referred to the Cardio-Pulmonary Department for an evaluation of the pulmonary circulation between 1997 and 2007; who's applied diagnostic criteria was the proposed by the American Thoracic Society for COPD.18All patients should have the following inclusion criteria: 1) Class I - II NYHA/WHO system. 2) None should have a history of atopy or received drugs susceptible of having a vasodilator effect. 3) Absence of a respiratory infection/RV failure syndrome within twelve weeks prior the study. 4) Nonexistence of systemic arterial hypertension, valvular heart, coronary artery or primary myocardial diseases and, 5) Evidence of RV hypertrophy/dilatation, on the basis of either electrocardiographic/echocardiographic methods.The methodology for lung function test, for the analysis of blood/expired gases and for normal values of blood-gas exchange at our moderate altitude has been previously published.19,20 Pulmonary function results were compared with the normal values reported by Comroe,21 Baldwing22 and Morris23 and expressed as a percentage of the predicted normal value. For all patients it was its first admission to our institution and were treated before with conventional therapy. This therapy included inhaled bronchodilators, antibiotic agents and mild diuretic as each patient's clinical status indicated. They used supplemental oxygen therapy very irregularly and none were previously on a currently accepted LTOT program.12-16To compare the results obtained for the pressure/ flow for the studied PH - COPD patients, we analyzed the pressure/flow in 66 normal subjects (20 to 64 years of age); where 40 cases were collected form the literature; (6 from Harris,2 4 from Lewis,24 3 from Riley,25 8 from Hickam,26 5 from Slonin,27 7 from Fishman,28 7 from Dexter29) and from 26 healthy volunteers studied at our institution. Also, we compare our results obtained for the pressure/flow from 70 COPD patients where the pertinent pulmonary hemodynamic information could be individually analyzed published by Emirgil30 (n = 6), Evans31 (n = 7), Khaja32 (n = 3), Kitchin33 (n = 2) and by Williams34 (n = 52). Hemodynamic and exercise measurements. All the procedures were explained in detail and informed consent was obtained for all patients. Our procedure for RHC at rest and during steady - state - exercise has been previously described.19,20 Briefly, all patients were studied in the morning, in the fasting, non-sedated state. Supplemental oxygen therapy was discontinued 4 hours before the RHC study. The hemodynamic evaluation was done with the patient in the supine position and according to the protocol part while breathing room air, on oxygen 99.5% and then after receiving supplemental oxygen by nasal prongs at rest. Pulmonary vascular pressures were measured at end-expiration and sampled at 200 Hz using an analog/digital converter and stored and analyzed on a personal computer. The following measurements were obtained: mPAP, mean pulmonary wedge pressure (mPWP) and mean systemic arterial pressure (mSAP). Cardiac output (CO) was measured by triplicate by the thermodilution method. For 99.5% O2 breathing, the mixture was inspired throughout a non-rebreathing valve from a reservoir bag (surrounded by atmospheric pressure) during 15 minutes previous to the hemodynamic basal measurements and then after while exercising. Study protocol. Before the hemodynamic study all patients were familiarized with the exercise technique. After steady-state conditions were ensured (stable heart rate (HR), CO, mPAP and mSAP for 10 minutes) a baseline set of hemodynamic measurements, expired gases and blood samples were obtained over - 1 minute period (resting baseline measurements). Systemic and pulmonary pressures were measured by averaging over 3 normal respiratory cycles. After 30 minutes equilibration period between each exercise protocol part, the measurements were then repeated pedaling in the supine position on a bicycle-ergometer for at least 6 minutes [maximum 9 minutes] at a load of 35 W to 40 W; during the following conditions: 1) breathing room air and 2) on 99.5% O2 . The exercise level was so selected that no more than mild to moderate dyspnea or fatigue appeared for all studied patients. An exercise set of hemodynamic measurements, expired gases and blood samples were never collected before 5 minutes of completed exercise (exercise measurements). The collection period for all exercise measurements starts at the moment when the patient refer by a pre-established signal dyspnea/fatigue, and was never <1 minute (maximum 3 minutes). In order that the work done in the two exercise periods should be equal the rate of peddling were kept constant during exercising. One hour after the last exercise test, while breathing room air, resting baseline measurements was repeated. Supplemental oxygen was initiated and maintained for 4 hours to 6 hours and a second set of measurements were repeated. Each patient received the lowest flow in whole L/min (3 to 4 L/min) that demonstrably increased resting, semi recumbent PaO2 of 65 mmHg to 70 mmHg. Data analysis. We analyzed the hemodynamic characteristics for the whole cohort and separately for each group PH - COPD patients (with resting < or > 30 mmHg mPAP). The stated results at rest/exercise while breathing room air, oxygen 99.5%, at rest breathing room air and supplemental oxygen represent the average of 3 clustered measurements with less than 10% variation. Harvey and Enson,35 equations were used to assess the relative roles played by active and passive factors for PH genesis. Plot and interpretation for mPAP/CI and Pext. The mPAP/CI coordinate generated from the resting state to the exercise condition was evaluated by linear regression analysis.36 The slope obtained was considered to be "the true PVR".1 Yield mPAP/CI - 95% confidence interval (CI) was analyzed for all the cohort and for each group.The following steps were followed for the construction of the pressure/flow picture: 1) the average-mPAP+1SD obtained from the resting-exercising maneuver was located in the pressure/CI diagram. 2) The slope was drawn. 3) Pext was traced and 4) CI ± 1SD was over printed on the slope line (solid gross line).If the tested mPAP/CI - 95% CI were located outside for that derived for the normal population it was consider to be an increased linear PVR. It was considered non similar between or among groups: if, the tested mPAP/CI -95% CI was statistically different located in relation to the control. Slope 95% CI values were considered non similar if they were statistically different from the control. Pext was considered abnormal for >10 mmHg values,1,9-11 and dissimilar if Pext ± 1SD was significant statistically different in relation to the evaluated. Vascular pulmonary vasomotion was considered to occur if, a significant statistical decrease/increase occurs for mPAP/ CI - 95% CI tested in relation to the control (i.e. if the mPAP/CI 95% CI constructed breathing air do not overlap with the obtained breathing oxygen). Statistical analysis. Continuous data are expressed as mean 1 ± SD. Independent Student t test, 1 way ANOVA (for multiple comparison Bonferroni's Test (i.e. baseline condition vs. exercise during air or oxygen breathing), X2, or Fisher exact test was used as appropriate. Correlations were calculated using Pearson´s correlation test, p values <0.05 were accepted as indicating statistical significance. Analyses were performed by using of SPSS-13 and STATA-9 software. Results Clinical and pulmonary function data. All patients were ex-smokers with a history of smoking equivalent to at least 20 pack-years. The mean age of the studied population was 59y ± 4y, the estimated symptom duration was 12y and male population predominate over females (2.3/1). Previous respiratory infections or the clinical syndrome of RV failure were observed in 75% and 40%, respectively. According to the NYHA/ WHO system 77.5% of the patients were in class II. Increased residual volume (Rvo), abnormal FEV1/VC ratio and FEF25-75 and decreased MBC were noted for all COPD patients. For COPD patients with a resting >30 mmHg mPAP NYHA/WHO class II and at least one previous respiratory infection treated without respiratory mechanical assistance were more frequently observed; for measurements like VC, Rvo, FEV1 , FEV1/VC and FEF25-75, all were more abnormal when compared to the measured for <30 mmHg mPAP COPD patients (Table 1). <img src="293v81n03-90028657fig1.jpg" alt="Table 1. Clinical, demographic and pulmonary function test data."></img>Hemodynamic/blood gas exchange data at rest and during exercise breathing room air. For all patients, hypoxemia at rest (PaO2 <67 ± 2.5 mmHg)19,20 that worse-ned with exercise associated with a decrease in SvO2 was a constant feature. During exercise a significant increase for mPAP and CI was associated with an increase for VO2 (from 208 ± 38 to 602 ± 44 mL/min, p <0.02). For all patients the increased noted for mPWP was <12 mmHg during exercise (Table 2). A significant negative correlation between FEV1 and mPAP was found (r = -0.63, p <0.05). A significant positive correlation between calculated and measured diastolic-PAP and dPAP-mPWP was found (r = 0.72, r = 0.74, respectively, p <0.001).<img src="293v81n03-90028657fig2.jpg" alt="Table 2. Hemodynamic and blood gas exchange data at rest and during exercise breathing room air and FiO2 99.5%"></img>Hemodynamic and blood gas exchange data at rest and at exercise during oxygen breathing. After 15 minutes 99.5% O2 breathing at rest, a significant decrease for mPAP, CI, dPAP-mPWP, and HR were documented, associated with a significant increase in PaO2, SaO2 and SvO2 when compared to breathing room in the resting state. During exercise a significant increase for mPAP, CI, mPWP level (that remains <10 mmHg), dPAP-mPWP and HR was observed associated with a decrease in PaCO2 and SvO2 when compared to the resting condition breathing 99.5% O2 (Table 2). When we compare both exercise conditions, mPAP increase less while breathing oxygen (p <0.02), and was not associated with arterial hypoxemia or a significant change for PaCO2 and arterial pH. SvO2 remain increased when compared to the recorded breathing room air at exercise (Table 2).mPAP/CI and Pext results. mPAP/CI-95%CI location, slope and Pext were abnormal for all PH - COPD patients breathing room air. Breathing oxygen 99.5% a significant decrease for the mPAP/CI - 95% CI in parallel was documented not associated with a slope or a Pext change (Table 3, Figure 1).<img src="293v81n03-90028657fig3.jpg" alt="Table 3. mPAP/CI and Pext results breathing room air and FiO2 99.5% in PH-COPD patients."></img><img src="293v81n03-90028657fig4.jpg" alt="Figure 1. PH-COPD patients showed an abnormal mPAP/CI (linear PVR) location, slope and Pext when compared to normal subjects (in black). A significant decrease in parallel for the mPAP/CI (without a slope change) and without Pext change is observed breathing oxygen (in grey)."></img>Figure 1. PH-COPD patients showed an abnormal mPAP/CI (linear PVR) location, slope and Pext when compared to normal subjects (in black). A significant decrease in parallel for the mPAP/CI (without a slope change) and without Pext change is observed breathing oxygen (in grey).When COPD patients were separated in those with resting or 30 mmHg mPAP, for the first cohort it was noted a significant decline in average-mPAP (12.3 mmHg, p <0.004) associated with a significant slope decrease (p <0.008), a down-ward mPAP/CI - 95% CI displacement and a Pext decrease in relation to breathing room air. For the >30mmHg mPAP group, a non-significant decrease for the average-mPAP (3.3 mmHg, p = 0.23) with no change for the mPAP/CI - 95% CI location, associated with a slope trend to decrease and an increase in Pext in relation to breathing room air was documented.When we compare PH-COPD patients with resting mPAP or 30 mmHg, significant differences for mPAP/CI -95% CI location, for the average-mPAP and Pext values (19.5 ± 6 vs. 41.2 ± 11.5 mmHg; 4.7 ± 1.4 vs. 20.6 ± 4.9 mmHg; respectively, p <0.001 for all comparisons), without Sp differences between the two cohorts were found during 99.5% O2 breathing (Table 4, Figure 2). <img src="293v81n03-90028657fig5.jpg" alt="Table 4. mPAP/CI and Pext results breathing room air and FiO2 99.5% for COPD patients with resting or 30mmHg mPAP."></img><img src="293v81n03-90028657fig6.jpg" alt="Figure 2. A non-significant decrease linear PVR is documented for COPD patients with a resting mPAP >30 mmHg during 99.5% oxygen breathing (in gray). On the contrary, for those with a resting mPAP <30 mmHg, a significant decrease for linear PVR was observed (in gray). Therefore, RV hemodynamic benefit on afterload could be predicted for LTOT only for COPD patients with a resting mPAP of <30 mmHg. "></img>Figure 2. A non-significant decrease linear PVR is documented for COPD patients with a resting mPAP >30 mmHg during 99.5% oxygen breathing (in gray). On the contrary, for those with a resting mPAP <30 mmHg, a significant decrease for linear PVR was observed (in gray). Therefore, RV hemodynamic benefit on afterload could be predicted for LTOT only for COPD patients with a resting mPAP of <30 mmHg. Hemodynamic and blood gas exchange data during air and supplemental oxygen breathing at rest. Hemodynamic and blood gas exchange data at rest were not statistically different when compared to the recorded at the first resting baseline measurement during breathing air. After 4h to 6h of receiving supplemental oxygen, PaO2 increased (from 52 ± 3.9 to 67 ± 1.3 mmHg, p <0.001), SvO2, PaCO2 and arterial pH did not change (48 ± 2.3 vs. 47 ± 1.5%, p = 0.3; 35.2 ± 2.1 vs. 37.3 ± 4 mmHg, p = 0.2; 7.43 ± 0.02 vs. 7.41 ± 0.03 Units, p = 0.3; respectively). No differences for blood gas exchange after receiving supplemental oxygen were documented between resting or 30 mmHg mPAP PH - COPD patients.For the <30 mmHg mPAP group, a significant decrease for mPAP (8.9 ± 1.2 mmHg, p = 0.01) was associated with a CI decrease (0.48 ± 0.2 L min/m2, p <0.05) breathing supplemental oxygen when compared to breathing air. For the >30 mmHg mPAP group while breathing supplemental oxygen, mPAP and CI did not change in relation to breathing air (1.9 ± 0.3 mmHg, p = 0.1; 0.32 ± 0.1 L min/m2, p = 0.2; respectively). Hemoglobin (18.7 ± 0.6 g%), hematocrit (65 ± 1.7%) and cumulative fluid balance (1.4 ± 0.4 L) did not change during the different protocol parts. Comparison of our results in relation to the collected from literature. For the comparison of our results breathing room air in relation to the collected from literature we analyzed the studied normal population; and separate the COPD patients hemodynamically characterized: in those without resting or exercising PH (Group I), those without resting with exercising PH (Group II) and those with resting and exercising PH (Group III). Accordingly, the following hemodynamic information was derived.When we compare the mPAP/CI - 95% CI location and slope values for the collected normal population our results were not different from that published for normal healthy volunteers by Reeves and collaborators;37 and no differences were observed between the current cases collected from the literature vs. the volunteers studied at our moderate altitude. In relation to the previously mentioned COPD groups: 1) mPAP/CI - 95% CI abnormal location and slopes values for all COPD patients. 2) Increased slope values for Groups II - III in relation to Group I (p <0.01). 3) A progressive and significant mPAP/CI - 95% CI up-ward location for Group I in relation to our normal cases, for Group II in relation to Group I and for Group III in relation to Group II. 4) No slope differences between Group II and III (p = 0.1) associated with a Pext significant increase (p <0.001) and 5) no differences for the mPAP/CI - 95% CI location, for the slope or for Pext between Group III collected from the literature when compared to our Group III PH - COPD patients were documented (Table 5, Figure 3). <img src="293v81n03-90028657fig7.jpg" alt="Table 5. Comparison of normal individuals and COPD patients and between COPD patients without resting or exercising PH (Group - I), with those without resting with exercising PH (Group - II) and with resting and exercising PH (Group - III) and between group III COPD collected from the literature and the studied PH - COPD patients."></img><img src="293v81n03-90028657fig8.jpg" alt="Figure 3. It could be seen a progressive and significant mPAP/CI -95% CI up-ward location for Group I in relation to normal subjects, for Group II in relation to Group I, and for Group III in relation to Group II COPD patients. No differences between Groups III (from the literature (in gray) and our studied COPD patients (in black) were observed. "></img>Figure 3. It could be seen a progressive and significant mPAP/CI -95% CI up-ward location for Group I in relation to normal subjects, for Group II in relation to Group I, and for Group III in relation to Group II COPD patients. No differences between Groups III (from the literature (in gray) and our studied COPD patients (in black) were observed. Discussion The hemodynamic data collected from the studied COPD patients, who's hemodynamic profile was characterized by an abnormal mPAP at rest that increase with exercise, illustrate that when the pulmonary circulation in this part of the hemodynamic spectrum of the pulmonary circulation is investigated for PH - COPD, the location for mPAP/ CI, for the slope and for Pext value resulted abnormal as has been reported by other investigators.1-5,37 However, differences for linear PVR were observed among the studied PH-COPD patients, characterized by different mPAP/CI, slopes and Pext values when they were separated according to the resting mPAP level < or > 30 mmHg. Therefore, when considered PH-COPD, it is apparent that within the range of a normal mPWP, raised mPAP could result from both an increased in mPAP/CI and Pext for COPD who's mPAP >30 mmHg or could be solely the result from an increased mPAP/CI for those with a resting mPAP <30 mmHg. mPAP/Q and Pext interpretation. According to our results, mPAP/CI abnormal location, increased slopes and Pext values could not be only attributed to functional (endothelial vasoconstrictor-dilator imbalance, alveolar hypoxia as well as to pulmonary-exercise-vasoconstriction induced by a decrease in SvO2/sympathetic nervous system activation) abnormalities influences in the periphery of the pulmonary vasculature for all PH-COPD. Otherwise, could be also the result of the forces on the outside of the vessels, due to lung remodeling (inflammation-fibrosis) or mechanical abnormalities (increased pleural/alveolar pressure, over inflation, bronchial obstruction).1-7,38-42 Therefore, due to the numerous involvedness factors for PH genesis, for mPAP/Q and Pext abnormalities in this scenario, is not easy to accept we are just measuring always "the true arteriolar PVR" for all PH - COPD patients. Accordingly, it seems why for PH - COPD patients with a mPAP >30 mmHg, in addition to some non-hypoxemic active factors, or more probably due to factors like more severe bronchial obstruction/over-inflation when compared to those with a resting mPAP <30 mmHg higher slope values were documented. Moreover, according to our findings for slope values, for the mPAP/ CI location and Pext values results seems to depend on the pulmonary hemodynamic characteristic profile of the studied group PH-COPD patients; conditions that in turn seems to be associated with the pathological lung stage of the disease. Our results, support that "true arteriolar" resistance seems to be non-preponderant at advanced stage of this disease, as is supported by lack of vasodilatation (oxygen mediated) in a scenario were other non-active or fixed factors predominate in the genesis for linear PVR in PH-COPD with a mPAP >30 mmHg.1,5,6,38-42 Furthermore, histological studies, had shown that PH - COPD is not mainly a disease of the small muscular pulmonary arteries and arterioles; and the degree of vascular involvement is characterized essentially by medial hypertrophy in arteries and arterioles/cellular intimal proliferation in the smallest muscular arteries, arterioles; vascular pathological panorama that is not, or even close to the degree of vascular damage ascribed for Idiopathic-pulmonary artery hypertension patients which is considered the prototype of a more pure arteriolar pulmonary vascular disease.43,44 With the information collected from the literature and from our own data we demonstrate that COPD patients without resting or exercising PH (Group I) will exhibit lower slopes than those with those without resting with exercising PH (Group II) or with resting and exercising PH (Group III). Hemodynamic aspects that could result important in clinical practice in order to better define, at least in part, some of the current therapeutic strategies (like the impact of LTOT) for COPD patients. The measured mPAP in the stable state for COPD patients is often <35 mmHg, level for mPAP that is in close agreement with the observed for our studied PH-COPD patients (31.7 ± 8.2mmHg).12-17 LTOT significantly improves the survival of hypoxemic COPD patients, as demonstrated by NOTT and MRC trials.12-14 Remarkable, it has been observed that in COPD patients under LTOT, the 5y survival rate was 66% in those whose initial mPAP was <25 mmHg, but only 36% when initial mPAP was >25 mmHg.14 This improved prognosis could partly be explained by the reduction of episodes of the syndrome of RV failure under LTOT and the duration and the severity of alveolar hypoxia in these patients. However, according to our results and interpretation for the PVR nature, mPAP pointed prognostic information could also be due to the prevail influence of more advanced lung disease component over the "vascular-alveolar-hypoxic potentially reversible component" for stable PH - COPD patients, in a context where mPAP was >25 mmHg. More over for those PH - COPD patients included in NOTT and MRC trials, with a 29 mmHg to 35 mmHg mPAP, little change had been observed over the years for mPAP and only sometimes reverses the progression of PH.12-16 Observation that also give support for the non-preponderant vascular reactivity oxygen mediated PVR nature for PHCOPD patients whose resting mPAP is >30 mmHg. These observations suggest and support the opinion in relation to supplemental oxygen therapy,15-17 that LTOT should be started earlier in hypoxemic patients (with resting mPAP<30 mmHg) to achieve the reversal or lack for PH related to alveolar hypoxia/induced pulmonary-exercise-vasoconstriction induced by a decrease in SvO2 for PH - COPD patients. Hemodynamic therapeutic gold target that had not been demonstrated to our knowledge for PH - COPD under LTOT; and now is suggested on the mPAP/CI analysis basis for this group PH - COPD patients, where acute oxygen breathing/pulmonary hemodynamic effect benefit was demonstrated for COPD patients with a resting mPAP <30 mmHg. Moreover, our present observation could give support, at least in part, to the benefit in mortality referred by the NOTT group for those COPD patients with a baseline mPAP <27 mmHg (p = 0.03) and not for those with a mPAP >27 mmHg (p = 0.14),13 were the hemodynamic positive benefit on the pulmonary circulation and in consequence on RV afterload could account for a better long-term evolution for the resting mPAP <30 mmHg PH-COPD patients. Limitations. It is clear, we only studied linear PVR at a clinical mPAP/CI range, and the non-linear segment was not directly investigated at low flows due to the nature of the protocol used.2,9-11,45 Although, we analyzed mPAP/CI behavior for PH - COPD, due to the requisites to perform the exercise-technique, the derived results could only be applied for NYHA/WHO I - II classes PH - COPD stable patients. With the protocol used, we have to accept that this maneuver increase flow but also affect vascular tone due to exercise-induced-pulmonary-vasoconstriction.45 However, if this factor or others (like lung mechanics/ anatomical/blood-gas abnormalities) when present, are taken properly in consideration, will allow us to better precise the resistive information derived from mPAP/CI and in consequence will improve its clinical interpretation at the onset of LTOT. We also are aware, that the obtained "acute hemodynamic information of the pulmonary circulation" in relation to oxygen breathing, information that must be validated in the next coming future at short- and long-term in PH - COPD patients. ConclusionsAlthough, CO-exercise changes may led to spurious increased slopes in some PH patients, we demonstrate that when mPAP/CI are constructed according to the logistic provided and the derived information is analyzed in relation to PH pathogenesis, mPAP/CI could give a valuable information regarding the true linear PVR nature. We also found that mPAP/CI abnormalities, due to the influence of active/passive factors related to PH pathogenesis, could not only reflect precisely increased "true PVR for small muscular arteries/arterioles" in all the hemodynamic spectrum for PH - COPD. We should focus on resting mPAP values for PH - COPD patients, because for those with a resting <30 mmHg mPAP could probably benefit more with LTOT by in addition reducing RV afterload, hemodynamic condition which in turn should give a better long-term prognosis for this category PH - COPD patients.<hr></hr>Corresponding author: Eulo Lupi Herrera. Sur 136 N° 116. Col. Las Américas, 01120, México, D. F. México. Telephone: 52 308 000, ext. 3762. E-mail: <a href="mailto:elupiherrera@hotmail.com" class="elsevierStyleCrossRefs">elupiherrera@hotmail.com</a>.Received on April 16, 2009; accepted on March 30, 2011." "pdfFichero" => "293v81n03a90028657pdf001.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec192255" "palabras" => array:1 [ 0 => "Hipertensión pulmonar; Relación presión flujo; Oxígeno terapia; EPOC; México" ] ] ] "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec192256" "palabras" => array:1 [ 0 => "Pulmonary hypertension; Pressure/flow; Acute oxygen breathing; COPD; Mexico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "Objetivos: En esta investigación clínica-hemodinámica, analizamos la relación que se establece entre la presión arterial pulmonar media (PAPm) con la del índice cardiaco (IC), obtenida durante el ejercicio, con miras a expandir los conceptos relacionados con su propia naturaleza. Con ello, tratar de identificar mejor a los sujetos portadores de EPOC que se han caracterizado por ser respondedores durante la administración aguda de oxígeno (AAO2 - 99.5%). Métodos: Se obtuvieron la PAPm/IC y la presión extrapolada a cero flujo (Pext = bo)en 40 sujetos con EPOC y portadores de hipertensión pulmonar (HP) clínicamente estables, respirando aire ambiental (RAA) y bajo la influencia de la AAO2 - 99.5% en las condiciones de reposo y durante el ejercicio. Las características hemodinámicas se analizaron para toda la cohorte y para aquellos sujetos con PAPm en resposo < o > de 30 mmHg (Cohorte A y B, respectivamente). Resultados: La ubicación anormal de la PAPm/IC, de la pendiente (Sp: 5.77; 95% IC: 5.02 - 6.52 mmHg/L min/m2) y la de los valores para Pext (15.8 mmHg) se asociaron con: hipoxemia/ disminución de la presión venosa mezclada del O2, así como con anormalidades de la mecánica pulmonar. Condiciones hemodinámicas que no se modificaron para la Sp (5.47; 95% IC: 3.64 - 7.3 mmHg/L min/m2, p = 0.4) y la Pext (15.7 mmHg, p = 0.2); sin embargo, sí se vieron asociadas a una disminución significativa en paralelo de la PAPm/IC durante la AAO2 99.5%. Observaciones hemodinámicas que para la cohorte A, se caracterizaron por una reducción de la PAPm promedio (12.3 mmHg, p <0 004 por una disminución de la sp 6 02 95 ci: 4 04 - 8 a 3 11 49 mmhg l min m2 p <0 008 y por el descenso de pext 8 58 plusmn 3 a 4 7 1 mmhg p <0 01 al compararse con las documentadas raa en cambio para la cohorte b papm promedio y ic no se modificaron sp mostró sólo tendencia a disminuir p pext aumento de 12 plusmn 2 9 20 6 4 mmhg <0 03 en relación a las registradas raa bajo la aao2 - 99 5 se observaron diferencias significativas para papm ic 95 su localización promedio a: 19 plusmn 6 vs b: 41 2 11 mmhg p <0 001 y pext a: 4 7 plusmn 1 vs b: 20 6 9 mmhg p <0 001 y sin cambios en la sp entre cohorte a b conclusiones: cuando se analiza papm ic obtiene información que es valiosa para interpretar resistencia vascular pulmonar linear sujetos con epoc e hp embargo las anormalidades de no necesariamente reflejan aumento exclusivo arteriolar acuerdo observaciones agudas este estudio posiblemente solo sea esperarse beneficio oxigenoterapia largo plazo sobre circulación post-carga del ventrículo derecho aquellos portadores el reposo <30 mmhg</30> " ] "en" => array:1 [ "resumen" => "Objectives: We sought to analyze exercise-derived mean pulmonary artery pressure (Mpap) - cardiac index (CI) - relationship to expand the concepts regarding its nature and to better identify pulmonary hemodynamic responders to acute oxygen breathing (AOB - 99.5%) in pulmonary hypertension (PH) - COPD patients. Methods: mPAP/CI and extrapolated pressure (Pext) to zero flow were obtained breathing room air (BRA) and under AOB - 99.5% in 40 stable COPD patients with rest and exercise PH. Hemodynamic characteristics were analyzed for the entire cohort and separate for cases those with resting < or > 30 mmHg mPAP (cohort - A and B, respectively). Results: mPAP/CI abnormal location, slope (Sp: 5.77; 95% CI: 5.02 - 6.52 mmHg/L min/m2) and Pext values (15.8 mmHg) were associated with hypoxemia/decreased mixed venous - PO2 and lung mechanics abnormalities. Hemodynamic conditions that did not change for Sp (5.47; 95% CI: 3.64 - 7.3 mmHg/L min/m2, p = 0.4) and Pext (15.7 mmHg, p = 0.2) associated with a mPAP/CI significantly decrease in parallel during AOB - 99.5%. For cohort - A, an average-mPAP decline (12.3 mmHg, p <0 004 associated with a slope decrease from 6 02 95 ci: 4 04 - 8 to 3 11 49 mmhg l min m2 p <0 008 mpap ci - 95 down-ward displacement and pext decrease from 8 58 plusmn 3 to 4 7 1 mmhg p <0 01 in relation to bra were observed for cohort-b average-mpap and mpap ci - 95 location did not change sp show a trend decrease p pext significantly increase from 12 plusmn 2 9 20 6 4 mmhg <0 03 in relation to bra under aob - 99 5 significant differences for mpap ci 95 location average-mpap a: 19 plusmn 6 vs b: 41 2 11 mmhg p <0 001 and pext a: 4 7 plusmn 1 vs b: 20 6 9 mmhg p <0 001 without sp change between cohorts a and b were documented conclusions: when exercise derived mpap ci is analyzed valuable information for linear-pulmonary vascular resistance - lpvr could be obtained ph copd patients abnormalities not always reflect pure arteriolar increased all ph-copd hemodynamic benefit on the pulmonary circulation right ventricular afterload expected with long-term oxygen therapy in resting <30 mmhg mpap-ph-copd patients</30> " ] ] "multimedia" => array:8 [ 0 => array:8 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "293v81n03-90028657fig1.jpg" "imagenAlto" => 1404 "imagenAncho" => 1045 "imagenTamanyo" => 246769 ] ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical, demographic and pulmonary function test data." ] ] 1 => array:8 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "293v81n03-90028657fig2.jpg" "imagenAlto" => 1237 "imagenAncho" => 2087 "imagenTamanyo" => 372681 ] ] ] ] ] "descripcion" => array:1 [ "en" => "Hemodynamic and blood gas exchange data at rest and during exercise breathing room air and FiO2 99.5%" ] ] 2 => array:7 [ "identificador" => "fig1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "293v81n03-90028657fig3.jpg" "Alto" => 812 "Ancho" => 1025 "Tamanyo" => 123172 ] ] "descripcion" => array:1 [ "en" => "0028657fig3.jpg" width="1025" height="812" alt="Table 3. mPAP/CI and Pext results breath" ] ] 3 => array:7 [ "identificador" => "fig2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "293v81n03-90028657fig4.jpg" "Alto" => 1100 "Ancho" => 1050 "Tamanyo" => 151293 ] ] "descripcion" => array:1 [ "en" => "028657fig4.jpg" width="1050" height="1100" alt="Figure 1. PH-COPD patients showed an abnormal mPAP/CI (linear PVR) location, slope and Pext when compared to normal subjects (in black). A significant decrease in parallel for the mPAP/CI (without a slope change) and without Pex" ] ] 4 => array:7 [ "identificador" => "fig3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "293v81n03-90028657fig5.jpg" "Alto" => 750 "Ancho" => 2008 "Tamanyo" => 161456 ] ] "descripcion" => array:1 [ "en" => "0028657fig5.jpg" width="2008" height="750" alt="Table 4. mPAP/CI and Pext results breathing room air and FiO2 99.5" ] ] 5 => array:8 [ "identificador" => "fig4" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "293v81n03-90028657fig6.jpg" "Alto" => 950 "Ancho" => 1037 "Tamanyo" => 122625 ] ] "descripcion" => array:1 [ "en" => "A non-significant decrease linear PVR is documented for COPD patients with a resting mPAP >30 mmHg during 99.5% oxygen breathing (in gray). On the contrary, for those with a resting mPAP <30 mmHg, a significant decrease for linear PVR was observed (in gray). Therefore, RV hemodynamic benefit on afterload could be predicted for LTOT only for COPD patients with a resting mPAP of <30 mmHg." ] ] 6 => array:8 [ "identificador" => "tbl3" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "293v81n03-90028657fig7.jpg" "imagenAlto" => 808 "imagenAncho" => 2070 "imagenTamanyo" => 223237 ] ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison of normal individuals and COPD patients and between COPD patients without resting or exercising PH (Group - I), with those without resting with exercising PH (Group - II) and with resting and exercising PH (Group - III) and between group III COPD collected from the literature and the studied PH - COPD patients." ] ] 7 => array:7 [ "identificador" => "fig5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "293v81n03-90028657fig8.jpg" "Alto" => 908 "Ancho" => 1029 "Tamanyo" => 115697 ] ] "descripcion" => array:1 [ "en" => "0028657fig8.jpg" width="1029" height="908" alt="Figure 3. It could be seen a progressive and significant mPAP/CI -95% CI up-ward location for Group I in relation to normal subjects, for Group II in relation to Group I, and for Group III in relation to Group II COPD patients. No differences between Groups III (from the literature (in gray) and our" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:45 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "On pulmonary vascular resistance: the need for a more precise definition." 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The role of pulmonary pressure/cardiac index to identify pulmonary hemodynamic responders to acute oxygen breathing pulmonary hypertension COPD patients

Eulo Lupi-Herreraa, Julio Sandovalb, Luis Efren Santosb, Tomás Pulidob, Martín Rosas-Peraltac

a Sub-Direction of Clinical Investigation. Instituto Nacional de Cardiología Ignacio Chávez, México.

b Cardiopulmonary Department. Instituto Nacional de Cardiología Ignacio Chávez, México.

c Clinical Cardiology Department. Instituto Nacional de Cardiología Ignacio Chávez, México.

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          "en" => "0028657fig3&#46;jpg&#34; width&#61;&#34;1025&#34; height&#61;&#34;812&#34; alt&#61;&#34;Table 3&#46; mPAP&#47;CI and Pext results breath"
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introduction</span></p><p class="elsevierStylePara">Due to the meaningless significance of calculated pulmonary vascular resistance &#40;PVR&#41;&#44;<span class="elsevierStyleSup">1 </span>a bedside approach to get a deeper insight into the PVR linear component nature is based on the determination of multipoint mean pulmonary artery pressure &#40;mPAP&#41; - cardiac index &#40;CI&#41; - relationship&#46;<span class="elsevierStyleSup">2-5 </span>In most cardiac&#47;pulmonary diseases mPAP&#47;CI are well described by a linear approximation&#44; but their extrapolation to the pressure axis at zero flow &#40;Pext&#41; may be higher than pulmonary artery occluded pressure or left atrial pressure&#46;<span class="elsevierStyleSup">1&#44;2&#44;5 </span>An increased Pext could be explained by an increased mean closing pressure in small arterioles or capillaries &#40;or both&#41;&#44; or also could result from the forces on the outside of the vessels&#44; such as abnormal alveolar pressure on the pulmonary capillaries&#46;<span class="elsevierStyleSup">6-11</span> Approach for PVR determination&#44; that from time to time had been attempted in cohorts composed by few cases with pulmonary hypertension &#40;PH&#41; due to lung diseases in the last 40 years&#46; Although&#44; to our knowledge this hemodynamic approach has not been attempted to evaluate the acute role of oxygen according to mPAP level in PH chronic obstructive pulmonary disease &#40;COPD&#41; patients&#46;<span class="elsevierStyleSup">3-5</span> Information that could be important&#44; since it has been suggested that when resting mPAP is moderately to markedly elevated &#40;&#62;30 mmHg&#41; at the onset of long-term oxygen therapy &#40;LTOT&#41;&#44; the survival rate is decreased in comparison with patients with no or mild PH &#40;&#60;30 mmHg&#41;&#46;<span class="elsevierStyleSup">12-17</span> Accordingly&#44; it has been proposed that LTOT should be started earlier at the stage of mild &#40;or even absent&#41; PH to favor the long-term survival in hypoxemic COPD patients&#46;<span class="elsevierStyleSup">15</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Objective</span></p><p class="elsevierStylePara">To extend the limited clinical information in relation to multipoint mPAP&#47;CI in PH-COPD&#59; second&#44; if mPAP&#47;CI location&#44; the slope value and Pext analysis could help to better identify pulmonary vasomotion due to acute oxygen breathing and in consequence recognize which cases could be hemodynamically beneficiated by decreasing right ventricular &#40;RV&#41; afterload among PH-COPD patients&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Methods</span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Patients&#46; </span>The protocol was approved by the ethics review commission&#46; The series of studied patients &#40;n &#61; 40&#59; born&#44; raised and permanent residents of Mexico City &#40;altitude 2240 meters&#41;&#41; were selected from a group of 677 cases&#44; which represented the total number referred to the Cardio-Pulmonary Department for an evaluation of the pulmonary circulation between 1997 and 2007&#59; who&#39;s applied diagnostic criteria was the proposed by the American Thoracic Society for COPD&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">All patients should have the following inclusion criteria&#58; 1&#41; Class I - II NYHA&#47;WHO system&#46; 2&#41; None should have a history of atopy or received drugs susceptible of having a vasodilator effect&#46; 3&#41; Absence of a respiratory infection&#47;RV failure syndrome within twelve weeks prior the study&#46; 4&#41; Nonexistence of systemic arterial hypertension&#44; valvular heart&#44; coronary artery or primary myocardial diseases and&#44; 5&#41; Evidence of RV hypertrophy&#47;dilatation&#44; on the basis of either electrocardiographic&#47;echocardiographic methods&#46;</p><p class="elsevierStylePara">The methodology for lung function test&#44; for the analysis of blood&#47;expired gases and for normal values of blood-gas exchange at our <span class="elsevierStyleItalic">moderate altitude</span> has been previously published&#46;<span class="elsevierStyleSup">19&#44;20</span> Pulmonary function results were compared with the normal values reported by Comroe&#44;<span class="elsevierStyleSup">21</span> Baldwing<span class="elsevierStyleSup">22</span> and Morris<span class="elsevierStyleSup">23</span> and expressed as a percentage of the predicted normal value&#46; </p><p class="elsevierStylePara">For all patients it was its first admission to our institution and were treated before with conventional therapy&#46; This therapy included inhaled bronchodilators&#44; antibiotic agents and mild diuretic as each patient&#39;s clinical status indicated&#46; They used supplemental oxygen therapy very irregularly and none were previously on a currently accepted LTOT program&#46;<span class="elsevierStyleSup">12-16</span></p><p class="elsevierStylePara">To compare the results obtained for the pressure&#47; flow for the studied PH - COPD patients&#44; we analyzed the pressure&#47;flow in 66 normal subjects &#40;20 to 64 years of age&#41;&#59; where 40 cases were collected form the literature&#59; &#40;6 from Harris&#44;<span class="elsevierStyleSup">2</span> 4 from Lewis&#44;<span class="elsevierStyleSup">24</span> 3 from Riley&#44;<span class="elsevierStyleSup">25 </span>8 from Hickam&#44;<span class="elsevierStyleSup">26</span> 5 from Slonin&#44;<span class="elsevierStyleSup">27</span> 7 from Fishman&#44;<span class="elsevierStyleSup">28</span> 7 from Dexter<span class="elsevierStyleSup">29</span>&#41; and from 26 healthy volunteers studied at our institution&#46; Also&#44; we compare our results obtained for the pressure&#47;flow from 70 COPD patients where the pertinent pulmonary hemodynamic information could be individually analyzed published by Emirgil<span class="elsevierStyleSup">30 </span>&#40;n &#61; 6&#41;&#44; Evans<span class="elsevierStyleSup">31</span> &#40;n &#61; 7&#41;&#44; Khaja<span class="elsevierStyleSup">32</span> &#40;n &#61; 3&#41;&#44; Kitchin33 &#40;n &#61; 2&#41; and by Williams34 &#40;n &#61; 52&#41;&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Hemodynamic and exercise measurements&#46; </span>All the procedures were explained in detail and informed consent was obtained for all patients&#46; Our procedure for RHC at rest and during steady - state - exercise has been previously described&#46;<span class="elsevierStyleSup">19&#44;20</span> Briefly&#44; all patients were studied in the morning&#44; in the fasting&#44; non-sedated state&#46; Supplemental oxygen therapy was discontinued 4 hours before the RHC study&#46; The hemodynamic evaluation was done with the patient in the supine position and according to the protocol part while breathing room air&#44; on oxygen 99&#46;5&#37; and then after receiving supplemental oxygen by nasal prongs at rest&#46; Pulmonary vascular pressures were measured at end-expiration and sampled at 200 Hz using an analog&#47;digital converter and stored and analyzed on a personal computer&#46; The following measurements were obtained&#58; mPAP&#44; mean pulmonary wedge pressure &#40;mPWP&#41; and mean systemic arterial pressure &#40;mSAP&#41;&#46; Cardiac output &#40;CO&#41; was measured by triplicate by the thermodilution method&#46; For 99&#46;5&#37; O<span class="elsevierStyleInf">2</span> breathing&#44; the mixture was inspired throughout a non-rebreathing valve from a reservoir bag &#40;surrounded by atmospheric pressure&#41; during 15 minutes previous to the hemodynamic basal measurements and then after while exercising&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Study protocol&#46; </span>Before the hemodynamic study all patients were familiarized with the exercise technique&#46; After steady-state conditions were ensured &#40;stable heart rate &#40;HR&#41;&#44; CO&#44; mPAP and mSAP for 10 minutes&#41; a baseline set of hemodynamic measurements&#44; expired gases and blood samples were obtained over - 1 minute period &#40;<span class="elsevierStyleItalic">resting baseline measurements</span>&#41;&#46; Systemic and pulmonary pressures were measured by averaging over 3 normal respiratory cycles&#46; After 30 minutes equilibration period between each exercise protocol part&#44; the measurements were then repeated pedaling in the supine position on a bicycle-ergometer for at least 6 minutes &#91;maximum 9 minutes&#93; at a load of 35 W to 40 W&#59; during the following conditions&#58; 1&#41; breathing room air and 2&#41; on 99&#46;5&#37; O<span class="elsevierStyleInf">2</span> &#46; The exercise level was so selected that no more than mild to moderate dyspnea or fatigue appeared for all studied patients&#46; An exercise set of hemodynamic measurements&#44; expired gases and blood samples were never collected before 5 minutes of completed exercise &#40;<span class="elsevierStyleItalic">exercise measurements</span>&#41;&#46; The collection period for all exercise measurements starts at the moment when the patient refer by a pre-established signal dyspnea&#47;fatigue&#44; and was never &#60;1 minute &#40;maximum 3 minutes&#41;&#46; In order that the work done in the two exercise periods should be equal the rate of peddling were kept constant during exercising&#46; </p><p class="elsevierStylePara">One hour after the last exercise test&#44; while breathing room air&#44; resting baseline measurements was repeated&#46; Supplemental oxygen was initiated and maintained for 4 hours to 6 hours and a second set of measurements were repeated&#46; Each patient received the lowest flow in whole L&#47;min &#40;3 to 4 L&#47;min&#41; that demonstrably increased resting&#44; semi recumbent PaO<span class="elsevierStyleInf">2</span> of 65 mmHg to 70 mmHg&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Data analysis&#46; </span>We analyzed the hemodynamic characteristics for the whole cohort and separately for each group PH - COPD patients &#40;with resting &#60; or &#62; 30 mmHg mPAP&#41;&#46; The stated results at rest&#47;exercise while breathing room air&#44; oxygen 99&#46;5&#37;&#44; at rest breathing room air and supplemental oxygen represent the average of 3 clustered measurements with less than 10&#37; variation&#46; Harvey and Enson&#44;<span class="elsevierStyleSup">35 </span>equations were used to assess the relative roles played by active and passive factors for PH genesis&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Plot and interpretation for mPAP&#47;CI and Pext</span>&#46; The mPAP&#47;CI coordinate generated from the resting state to the exercise condition was evaluated by linear regression analysis&#46;<span class="elsevierStyleSup">36</span> The slope obtained was considered to be &#34;the true PVR&#34;&#46;<span class="elsevierStyleSup">1</span> Yield mPAP&#47;CI - 95&#37; confidence interval &#40;CI&#41; was analyzed for all the cohort and for each group&#46;</p><p class="elsevierStylePara">The following steps were followed for the construction of the pressure&#47;flow picture&#58; 1&#41; the average-mPAP&#43;1SD obtained from the resting-exercising maneuver was located in the pressure&#47;CI diagram&#46; 2&#41; The slope was drawn&#46; 3&#41; Pext was traced and 4&#41; CI &#177; 1SD was over printed on the slope line &#40;solid gross line&#41;&#46;</p><p class="elsevierStylePara">If the tested mPAP&#47;CI - 95&#37; CI were located outside for that derived for the normal population it was consider to be an increased linear PVR&#46; It was considered non similar between or among groups&#58; if&#44; the tested mPAP&#47;CI -95&#37; CI was statistically different located in relation to the control&#46; Slope 95&#37; CI values were considered non similar if they were statistically different from the control&#46; </p><p class="elsevierStylePara">Pext was considered abnormal for &#62;10 mmHg values&#44;<span class="elsevierStyleSup">1&#44;9-11</span> and dissimilar if Pext &#177; 1SD was significant statistically different in relation to the evaluated&#46; Vascular pulmonary vasomotion was considered to occur if&#44; a significant statistical decrease&#47;increase occurs for mPAP&#47; CI - 95&#37; CI tested in relation to the control &#40;i&#46;e&#46; if the mPAP&#47;CI 95&#37; CI constructed breathing air do not overlap with the obtained breathing oxygen&#41;&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Statistical analysis&#46; </span>Continuous data are expressed as mean 1 &#177; SD&#46; Independent Student <span class="elsevierStyleItalic">t </span>test&#44; 1 way ANOVA &#40;for multiple comparison Bonferroni&#39;s Test &#40;i&#46;e&#46; baseline condition <span class="elsevierStyleItalic">vs&#46;</span> exercise during air or oxygen breathing&#41;&#44; <span class="elsevierStyleItalic">X<span class="elsevierStyleSup">2</span></span>&#44; or Fisher exact test was used as appropriate&#46; Correlations were calculated using Pearson&#180;s correlation test&#44; <span class="elsevierStyleItalic">p</span> values &#60;0&#46;05 were accepted as indicating statistical significance&#46; Analyses were performed by using of SPSS-13 and STATA-9 software&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Results </span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Clinical and pulmonary function data&#46; </span>All patients were ex-smokers with a history of smoking equivalent to at least 20 pack-years&#46; The mean age of the studied population was 59y &#177; 4y&#44; the estimated symptom duration was 12y and male population predominate over females &#40;2&#46;3&#47;1&#41;&#46; Previous respiratory infections or the clinical syndrome of RV failure were observed in 75&#37; and 40&#37;&#44; respectively&#46; According to the NYHA&#47; WHO system 77&#46;5&#37; of the patients were in class II&#46; Increased residual volume &#40;Rvo&#41;&#44; abnormal FEV<span class="elsevierStyleInf">1</span>&#47;VC ratio and FEF<span class="elsevierStyleSup">25-75</span> and decreased MBC were noted for all COPD patients&#46; For COPD patients with a resting &#62;30 mmHg mPAP NYHA&#47;WHO class II and at least one previous respiratory infection treated without respiratory mechanical assistance were more frequently observed&#59; for measurements like VC&#44; Rvo&#44; FEV<span class="elsevierStyleInf">1</span> &#44; FEV<span class="elsevierStyleInf">1</span>&#47;VC and FEF<span class="elsevierStyleSup">25-75</span>&#44; all were more abnormal when compared to the measured for &#60;30 mmHg mPAP COPD patients &#40;<span class="elsevierStyleBold">Table 1</span>&#41;&#46; </p><p class="elsevierStylePara"><img src="293v81n03-90028657fig1.jpg" alt="Table 1&#46; Clinical&#44; demographic and pulmonary function test data&#46;"></img></p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Hemodynamic&#47;blood gas exchange data at rest and during exercise breathing room air&#46; </span>For all patients&#44; hypoxemia at rest &#40;PaO<span class="elsevierStyleInf">2</span> &#60;67 &#177; 2&#46;5 mmHg&#41;<span class="elsevierStyleSup">19&#44;20</span> that worse-ned with exercise associated with a decrease in SvO<span class="elsevierStyleInf">2</span> was a constant feature&#46; During exercise a significant increase for mPAP and CI was associated with an increase for VO<span class="elsevierStyleInf">2 </span> &#40;from 208 &#177; 38 to 602 &#177; 44 mL&#47;min&#44; <span class="elsevierStyleItalic">p</span> &#60;0&#46;02&#41;&#46; For all patients the increased noted for mPWP was &#60;12 mmHg during exercise &#40;<span class="elsevierStyleBold">Table 2</span>&#41;&#46; A significant negative correlation between FEV<span class="elsevierStyleInf">1</span> and mPAP was found &#40;r &#61; -0&#46;63&#44; <span class="elsevierStyleItalic">p</span> &#60;0&#46;05&#41;&#46; A significant positive correlation between calculated and measured diastolic-PAP and dPAP-mPWP was found &#40;r &#61; 0&#46;72&#44; r &#61; 0&#46;74&#44; respectively&#44; <span class="elsevierStyleItalic">p</span> &#60;0&#46;001&#41;&#46;</p><p class="elsevierStylePara"><img src="293v81n03-90028657fig2.jpg" alt="Table 2&#46; Hemodynamic and blood gas exchange data at rest and during exercise breathing room air and FiO2 99&#46;5&#37;"></img></p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Hemodynamic and blood gas exchange data at rest and at exercise during oxygen breathing&#46; </span>After 15 minutes 99&#46;5&#37; O<span class="elsevierStyleInf">2</span> breathing at rest&#44; a significant decrease for mPAP&#44; CI&#44; dPAP-mPWP&#44; and HR were documented&#44; associated with a significant increase in PaO<span class="elsevierStyleInf">2</span>&#44; SaO<span class="elsevierStyleInf">2</span> and SvO<span class="elsevierStyleInf">2 </span>when compared to breathing room in the resting state&#46; During exercise a significant increase for mPAP&#44; CI&#44; mPWP level &#40;that remains &#60;10 mmHg&#41;&#44; dPAP-mPWP and HR was observed associated with a decrease in PaCO<span class="elsevierStyleInf">2</span> and SvO<span class="elsevierStyleInf">2</span> when compared to the resting condition breathing 99&#46;5&#37; O<span class="elsevierStyleInf">2</span> &#40;<span class="elsevierStyleBold">Table 2</span>&#41;&#46; When we compare both exercise conditions&#44; mPAP increase less while breathing oxygen &#40;<span class="elsevierStyleItalic">p</span> &#60;0&#46;02&#41;&#44; and was not associated with arterial hypoxemia or a significant change for PaCO<span class="elsevierStyleInf">2</span> and arterial pH&#46; SvO<span class="elsevierStyleInf">2 </span>remain increased when compared to the recorded breathing room air at exercise &#40;<span class="elsevierStyleBold">Table 2</span>&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic">mPAP&#47;CI and Pext results&#46; </span>mPAP&#47;CI-95&#37;CI location&#44; slope and Pext were abnormal for all PH - COPD patients breathing room air&#46; Breathing oxygen 99&#46;5&#37; a significant decrease for the mPAP&#47;CI - 95&#37; CI in parallel was documented not associated with a slope or a Pext change &#40;<span class="elsevierStyleBold">Table 3&#44; Figure 1</span>&#41;&#46;</p><p class="elsevierStylePara"><img src="293v81n03-90028657fig3.jpg" alt="Table 3&#46; mPAP&#47;CI and Pext results breathing room air and FiO2 99&#46;5&#37; in PH-COPD patients&#46;"></img></p><p class="elsevierStylePara"><img src="293v81n03-90028657fig4.jpg" alt="Figure 1&#46; PH-COPD patients showed an abnormal mPAP&#47;CI &#40;linear PVR&#41; location&#44; slope and Pext when compared to normal subjects &#40;in black&#41;&#46; A significant decrease in parallel for the mPAP&#47;CI &#40;without a slope change&#41; and without Pext change is observed breathing oxygen &#40;in grey&#41;&#46;"></img></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Figure 1&#46;</span> PH-COPD patients showed an abnormal mPAP&#47;CI &#40;linear PVR&#41; location&#44; slope and Pext when compared to normal subjects &#40;in black&#41;&#46; A significant decrease in parallel for the mPAP&#47;CI &#40;without a slope change&#41; and without Pext change is observed breathing oxygen &#40;in grey&#41;&#46;</p><p class="elsevierStylePara">When COPD patients were separated in those with resting or 30 mmHg mPAP&#44; for the first cohort it was noted a significant decline in average-mPAP &#40;12&#46;3 mmHg&#44; <span class="elsevierStyleItalic">p</span> &#60;0&#46;004&#41; associated with a significant slope decrease &#40;<span class="elsevierStyleItalic">p</span> &#60;0&#46;008&#41;&#44; a down-ward mPAP&#47;CI - 95&#37; CI displacement and a Pext decrease in relation to breathing room air&#46; For the &#62;30mmHg mPAP group&#44; a non-significant decrease for the average-mPAP &#40;3&#46;3 mmHg&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;23&#41; with no change for the mPAP&#47;CI - 95&#37; CI location&#44; associated with a slope trend to decrease and an increase in Pext in relation to breathing room air was documented&#46;</p><p class="elsevierStylePara">When we compare PH-COPD patients with resting mPAP or 30 mmHg&#44; significant differences for mPAP&#47;CI -95&#37; CI location&#44; for the average-mPAP and Pext values &#40;19&#46;5 &#177; 6 <span class="elsevierStyleItalic">vs&#46; </span>41&#46;2 &#177; 11&#46;5 mmHg&#59; 4&#46;7 &#177; 1&#46;4 <span class="elsevierStyleItalic">vs&#46; </span>20&#46;6 &#177; 4&#46;9 mmHg&#59; respectively&#44; <span class="elsevierStyleItalic">p</span> &#60;0&#46;001 for all comparisons&#41;&#44; without Sp differences between the two cohorts were found during 99&#46;5&#37; O<span class="elsevierStyleInf">2</span> breathing &#40;<span class="elsevierStyleBold">Table 4</span>&#44;<span class="elsevierStyleBold"> Figure 2</span>&#41;&#46; </p><p class="elsevierStylePara"><img src="293v81n03-90028657fig5.jpg" alt="Table 4&#46; mPAP&#47;CI and Pext results breathing room air and FiO2 99&#46;5&#37; for COPD patients with resting or 30mmHg mPAP&#46;"></img></p><p class="elsevierStylePara"><img src="293v81n03-90028657fig6.jpg" alt="Figure 2&#46; A non-significant decrease linear PVR is documented for COPD patients with a resting mPAP &#62;30 mmHg during 99&#46;5&#37; oxygen breathing &#40;in gray&#41;&#46; On the contrary&#44; for those with a resting mPAP &#60;30 mmHg&#44; a significant decrease for linear PVR was observed &#40;in gray&#41;&#46; Therefore&#44; RV hemodynamic benefit on afterload could be predicted for LTOT only for COPD patients with a resting mPAP of &#60;30 mmHg&#46; "></img></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Figure 2&#46;</span> A non-significant decrease linear PVR is documented for COPD patients with a resting mPAP &#62;30 mmHg during 99&#46;5&#37; oxygen breathing &#40;in gray&#41;&#46; On the contrary&#44; for those with a resting mPAP &#60;30 mmHg&#44; a significant decrease for linear PVR was observed &#40;in gray&#41;&#46; Therefore&#44; RV hemodynamic benefit on afterload could be predicted for LTOT only for COPD patients with a resting mPAP of &#60;30 mmHg&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Hemodynamic and blood gas exchange data during air and supplemental oxygen breathing at rest&#46; </span>Hemodynamic and blood gas exchange data at rest were not statistically different when compared to the recorded at the first resting baseline measurement during breathing air&#46; After 4h to 6h of receiving supplemental oxygen&#44; PaO<span class="elsevierStyleInf">2</span> increased &#40;from 52 &#177; 3&#46;9 to 67 &#177; 1&#46;3 mmHg&#44; <span class="elsevierStyleItalic">p</span> &#60;0&#46;001&#41;&#44; SvO2&#44; PaCO<span class="elsevierStyleInf">2</span> and arterial pH did not change &#40;48 &#177; 2&#46;3 <span class="elsevierStyleItalic">vs</span>&#46; 47 &#177; 1&#46;5&#37;&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;3&#59; 35&#46;2 &#177; 2&#46;1 <span class="elsevierStyleItalic">vs&#46;</span> 37&#46;3 &#177; 4 mmHg&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;2&#59; 7&#46;43 &#177; 0&#46;02 <span class="elsevierStyleItalic">vs&#46;</span> 7&#46;41 &#177; 0&#46;03 Units&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;3&#59; respectively&#41;&#46; No differences for blood gas exchange after receiving supplemental oxygen were documented between resting or 30 mmHg mPAP PH - COPD patients&#46;For the &#60;30 mmHg mPAP group&#44; a significant decrease for mPAP &#40;8&#46;9 &#177; 1&#46;2 mmHg&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;01&#41; was associated with a CI decrease &#40;0&#46;48 &#177; 0&#46;2 L min&#47;m<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">p</span> &#60;0&#46;05&#41; breathing supplemental oxygen when compared to breathing air&#46; For the &#62;30 mmHg mPAP group while breathing supplemental oxygen&#44; mPAP and CI did not change in relation to breathing air &#40;1&#46;9 &#177; 0&#46;3 mmHg&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;1&#59; 0&#46;32 &#177; 0&#46;1 L min&#47;m2&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;2&#59; respectively&#41;&#46; Hemoglobin &#40;18&#46;7 &#177; 0&#46;6 g&#37;&#41;&#44; hematocrit &#40;65 &#177; 1&#46;7&#37;&#41; and cumulative fluid balance &#40;1&#46;4 &#177; 0&#46;4 L&#41; did not change during the different protocol parts&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Comparison of our results in relation to the collected from literature&#46;</span> For the comparison of our results breathing room air in relation to the collected from literature we analyzed the studied normal population&#59; and separate the COPD patients hemodynamically characterized&#58; in those without resting or exercising PH &#40;Group I&#41;&#44; those without resting with exercising PH &#40;Group II&#41; and those with resting and exercising PH &#40;Group III&#41;&#46; Accordingly&#44; the following hemodynamic information was derived&#46;</p><p class="elsevierStylePara">When we compare the mPAP&#47;CI - 95&#37; CI location and slope values for the collected normal population our results were not different from that published for normal healthy volunteers by Reeves and collaborators&#59;<span class="elsevierStyleSup">37</span> and no differences were observed between the current cases collected from the literature <span class="elsevierStyleItalic">vs&#46;</span> the volunteers studied at our moderate altitude&#46; </p><p class="elsevierStylePara">In relation to the previously mentioned COPD groups&#58; 1&#41; mPAP&#47;CI - 95&#37; CI abnormal location and slopes values for all COPD patients&#46; 2&#41; Increased slope values for Groups II - III in relation to Group I &#40;<span class="elsevierStyleItalic">p</span> &#60;0&#46;01&#41;&#46; 3&#41; A progressive and significant mPAP&#47;CI - 95&#37; CI up-ward location for Group I in relation to our normal cases&#44; for Group II in relation to Group I and for Group III in relation to Group II&#46; 4&#41; No slope differences between Group II and III &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;1&#41; associated with a Pext significant increase &#40;<span class="elsevierStyleItalic">p</span> &#60;0&#46;001&#41; and 5&#41; no differences for the mPAP&#47;CI - 95&#37; CI location&#44; for the slope or for Pext between Group III collected from the literature when compared to our Group III PH - COPD patients were documented &#40;<span class="elsevierStyleBold">Table 5&#44; Figure 3</span>&#41;&#46; </p><p class="elsevierStylePara"><img src="293v81n03-90028657fig7.jpg" alt="Table 5&#46; Comparison of normal individuals and COPD patients and between COPD patients without resting or exercising PH &#40;Group - I&#41;&#44; with those without resting with exercising PH &#40;Group - II&#41; and with resting and exercising PH &#40;Group - III&#41; and between group III COPD collected from the literature and the studied PH - COPD patients&#46;"></img></p><p class="elsevierStylePara"><img src="293v81n03-90028657fig8.jpg" alt="Figure 3&#46; It could be seen a progressive and significant mPAP&#47;CI -95&#37; CI up-ward location for Group I in relation to normal subjects&#44; for Group II in relation to Group I&#44; and for Group III in relation to Group II COPD patients&#46; No differences between Groups III &#40;from the literature &#40;in gray&#41; and our studied COPD patients &#40;in black&#41; were observed&#46; "></img></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Figure 3&#46; </span>It could be seen a progressive and significant mPAP&#47;CI -95&#37; CI up-ward location for Group I in relation to normal subjects&#44; for Group II in relation to Group I&#44; and for Group III in relation to Group II COPD patients&#46; No differences between Groups III &#40;from the literature &#40;in gray&#41; and our studied COPD patients &#40;in black&#41; were observed&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Discussion </span></p><p class="elsevierStylePara">The hemodynamic data collected from the studied COPD patients&#44; who&#39;s hemodynamic profile was characterized by an abnormal mPAP at rest that increase with exercise&#44; illustrate that when the pulmonary circulation in this part of the hemodynamic spectrum of the pulmonary circulation is investigated for PH - COPD&#44; the location for mPAP&#47; CI&#44; for the slope and for Pext value resulted abnormal as has been reported by other investigators&#46;<span class="elsevierStyleSup">1-5&#44;37</span> However&#44; differences for linear PVR were observed among the studied PH-COPD patients&#44; characterized by different mPAP&#47;CI&#44; slopes and Pext values when they were separated according to the resting mPAP level &#60; or &#62; 30 mmHg&#46; Therefore&#44; when considered PH-COPD&#44; it is apparent that within the range of a normal mPWP&#44; raised mPAP could result from both an increased in mPAP&#47;CI and Pext for COPD who&#39;s mPAP &#62;30 mmHg or could be solely the result from an increased mPAP&#47;CI for those with a resting mPAP &#60;30 mmHg&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleItalic">mPAP&#47;Q and Pext interpretation&#46; </span>According to our results&#44; mPAP&#47;CI abnormal location&#44; increased slopes and Pext values could not be only attributed to functional &#40;endothelial vasoconstrictor-dilator imbalance&#44; alveolar hypoxia as well as to pulmonary-exercise-vasoconstriction induced by a decrease in SvO<span class="elsevierStyleInf">2</span>&#47;sympathetic nervous system activation&#41; abnormalities influences in the periphery of the pulmonary vasculature for all PH-COPD&#46; Otherwise&#44; could be also the result of the forces on the outside of the vessels&#44; due to lung remodeling &#40;inflammation-fibrosis&#41; or mechanical abnormalities &#40;increased pleural&#47;alveolar pressure&#44; over inflation&#44; bronchial obstruction&#41;&#46;<span class="elsevierStyleSup">1-7&#44;38-42 </span>Therefore&#44; due to the numerous involvedness factors for PH genesis&#44; for mPAP&#47;Q and Pext abnormalities in this scenario&#44; is not easy to accept we are just measuring always &#34;the true arteriolar PVR&#34; for all PH - COPD patients&#46; Accordingly&#44; it seems why for PH - COPD patients with a mPAP &#62;30 mmHg&#44; in addition to some non-hypoxemic active factors&#44; or more probably due to factors like more severe bronchial obstruction&#47;over-inflation when compared to those with a resting mPAP &#60;30 mmHg higher slope values were documented&#46; Moreover&#44; according to our findings for slope values&#44; for the mPAP&#47; CI location and Pext values results seems to depend on the pulmonary hemodynamic characteristic profile of the studied group PH-COPD patients&#59; conditions that in turn seems to be associated with the pathological lung stage of the disease&#46; Our results&#44; support that &#34;true arteriolar&#34; resistance seems to be non-preponderant at advanced stage of this disease&#44; as is supported by lack of vasodilatation &#40;oxygen mediated&#41; in a scenario were other non-active or fixed factors predominate in the genesis for linear PVR in PH-COPD with a mPAP &#62;30 mmHg&#46;<span class="elsevierStyleSup">1&#44;5&#44;6&#44;38-42 </span>Furthermore&#44; histological studies&#44; had shown that PH - COPD is not mainly a disease of the small muscular pulmonary arteries and arterioles&#59; and the degree of vascular involvement is characterized essentially by medial hypertrophy in arteries and arterioles&#47;cellular intimal proliferation in the smallest muscular arteries&#44; arterioles&#59; vascular pathological panorama that is not&#44; or even close to the degree of vascular damage ascribed for Idiopathic-pulmonary artery hypertension patients which is considered the prototype of a more pure arteriolar pulmonary vascular disease&#46;<span class="elsevierStyleSup">43&#44;44</span> With the information collected from the literature and from our own data we demonstrate that COPD patients without resting or exercising PH &#40;Group I&#41; will exhibit lower slopes than those with those without resting with exercising PH &#40;Group II&#41; or with resting and exercising PH &#40;Group III&#41;&#46; Hemodynamic aspects that could result important in clinical practice in order to better define&#44; at least in part&#44; some of the current therapeutic strategies &#40;like the impact of LTOT&#41; for COPD patients&#46; </p><p class="elsevierStylePara">The measured mPAP in the stable state for COPD patients is often &#60;35 mmHg&#44; level for mPAP that is in close agreement with the observed for our studied PH-COPD patients &#40;31&#46;7 &#177; 8&#46;2mmHg&#41;&#46;<span class="elsevierStyleSup">12-17</span> LTOT significantly improves the survival of hypoxemic COPD patients&#44; as demonstrated by NOTT and MRC trials&#46;<span class="elsevierStyleSup">12-14</span> Remarkable&#44; it has been observed that in COPD patients under LTOT&#44; the 5y survival rate was 66&#37; in those whose initial mPAP was &#60;25 mmHg&#44; but only 36&#37; when initial mPAP was &#62;25 mmHg&#46;<span class="elsevierStyleSup">14</span> This improved prognosis could partly be explained by the reduction of episodes of the syndrome of RV failure under LTOT and the duration and the severity of alveolar hypoxia in these patients&#46; However&#44; according to our results and interpretation for the PVR nature&#44; mPAP pointed prognostic information could also be due to the prevail influence of more advanced lung disease component over the &#34;vascular-alveolar-hypoxic potentially reversible component&#34; for stable PH - COPD patients&#44; in a context where mPAP was &#62;25 mmHg&#46; More over for those PH - COPD patients included in NOTT and MRC trials&#44; with a 29 mmHg to 35 mmHg mPAP&#44; little change had been observed over the years for mPAP and only sometimes reverses the progression of PH&#46;<span class="elsevierStyleSup">12-16 </span>Observation that also give support for the non-preponderant vascular reactivity oxygen mediated PVR nature for PHCOPD patients whose resting mPAP is &#62;30 mmHg&#46; </p><p class="elsevierStylePara"> These observations suggest and support the opinion in relation to supplemental oxygen therapy&#44;<span class="elsevierStyleSup">15-17</span> that LTOT should be started earlier in hypoxemic patients &#40;with resting mPAP&#60;30 mmHg&#41; to achieve the reversal or lack for PH related to alveolar hypoxia&#47;induced pulmonary-exercise-vasoconstriction induced by a decrease in SvO<span class="elsevierStyleInf">2</span> for PH - COPD patients&#46; Hemodynamic therapeutic gold target that had not been demonstrated to our knowledge for PH - COPD under LTOT&#59; and now is suggested on the mPAP&#47;CI analysis basis for this group PH - COPD patients&#44; where acute oxygen breathing&#47;pulmonary hemodynamic effect benefit was demonstrated for COPD patients with a resting mPAP &#60;30 mmHg&#46; Moreover&#44; our present observation could give support&#44; at least in part&#44; to the benefit in mortality referred by the NOTT group for those COPD patients with a baseline mPAP &#60;27 mmHg &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;03&#41; and not for those with a mPAP &#62;27 mmHg &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;14&#41;&#44;13 were the hemodynamic positive benefit on the pulmonary circulation and in consequence on RV afterload could account for a better long-term evolution for the resting mPAP &#60;30 mmHg PH-COPD patients&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Limitations&#46; </span>It is clear&#44; we only studied linear PVR at a clinical mPAP&#47;CI range&#44; and the non-linear segment was not directly investigated at low flows due to the nature of the protocol used&#46;<span class="elsevierStyleSup">2&#44;9-11&#44;45</span> Although&#44; we analyzed mPAP&#47;CI behavior for PH - COPD&#44; due to the requisites to perform the exercise-technique&#44; the derived results could only be applied for NYHA&#47;WHO I - II classes PH - COPD stable patients&#46; With the protocol used&#44; we have to accept that this maneuver increase flow but also affect vascular tone due to exercise-induced-pulmonary-vasoconstriction&#46;<span class="elsevierStyleSup">45 </span> However&#44; if this factor or others &#40;like lung mechanics&#47; anatomical&#47;blood-gas abnormalities&#41; when present&#44; are taken properly in consideration&#44; will allow us to better precise the resistive information derived from mPAP&#47;CI and in consequence will improve its clinical interpretation at the onset of LTOT&#46; We also are aware&#44; that the obtained &#34;acute hemodynamic information of the pulmonary circulation&#34; in relation to oxygen breathing&#44; information that must be validated in the next coming future at short- and long-term in PH - COPD patients&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conclusions</span></p><p class="elsevierStylePara">Although&#44; CO-exercise changes may led to spurious increased slopes in some PH patients&#44; we demonstrate that when mPAP&#47;CI are constructed according to the logistic provided and the derived information is analyzed in relation to PH pathogenesis&#44; mPAP&#47;CI could give a valuable information regarding the true linear PVR nature&#46; We also found that mPAP&#47;CI abnormalities&#44; due to the influence of active&#47;passive factors related to PH pathogenesis&#44; could not only reflect precisely increased &#34;true PVR for small muscular arteries&#47;arterioles&#34; in all the hemodynamic spectrum for PH - COPD&#46; We should focus on resting mPAP values for PH - COPD patients&#44; because for those with a resting &#60;30 mmHg mPAP could probably benefit more with LTOT by in addition reducing RV afterload&#44; hemodynamic condition which in turn should give a better long-term prognosis for this category PH - COPD patients&#46;</p><hr></hr><p class="elsevierStylePara"><span class="elsevierStyleBold">Corresponding author&#58; </span>Eulo Lupi Herrera&#46; <br></br> Sur 136 N&#176; 116&#46; Col&#46; Las Am&#233;ricas&#44; 01120&#44; M&#233;xico&#44; D&#46; F&#46; M&#233;xico&#46; <br></br> Telephone&#58; 52 308 000&#44; ext&#46; 3762&#46; <br></br> E-mail&#58; <a href="mailto&#58;elupiherrera&#64;hotmail&#46;com" class="elsevierStyleCrossRefs">elupiherrera&#64;hotmail&#46;com</a>&#46;</p><p class="elsevierStylePara">Received on April 16&#44; 2009&#59; <br></br> accepted on March 30&#44; 2011&#46;</p>"
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        "resumen" => "Objetivos&#58; En esta investigaci&#243;n cl&#237;nica-hemodin&#225;mica&#44; analizamos la relaci&#243;n que se establece entre la presi&#243;n arterial pulmonar media &#40;PAPm&#41; con la del &#237;ndice cardiaco &#40;IC&#41;&#44; obtenida durante el ejercicio&#44; con miras a expandir los conceptos relacionados con su propia naturaleza&#46; Con ello&#44; tratar de identificar mejor a los sujetos portadores de EPOC que se han caracterizado por ser respondedores durante la administraci&#243;n aguda de ox&#237;geno &#40;AAO2 - 99&#46;5&#37;&#41;&#46; M&#233;todos&#58; Se obtuvieron la PAPm&#47;IC y la presi&#243;n extrapolada a cero flujo &#40;Pext &#61; bo&#41;en 40 sujetos con EPOC y portadores de hipertensi&#243;n pulmonar &#40;HP&#41; cl&#237;nicamente estables&#44; respirando aire ambiental &#40;RAA&#41; y bajo la influencia de la AAO2 - 99&#46;5&#37; en las condiciones de reposo y durante el ejercicio&#46; Las caracter&#237;sticas hemodin&#225;micas se analizaron para toda la cohorte y para aquellos sujetos con PAPm en resposo &#60; o &#62; de 30 mmHg &#40;Cohorte A y B&#44; respectivamente&#41;&#46; Resultados&#58; La ubicaci&#243;n anormal de la PAPm&#47;IC&#44; de la pendiente &#40;Sp&#58; 5&#46;77&#59; 95&#37; IC&#58; 5&#46;02 - 6&#46;52 mmHg&#47;L min&#47;m2&#41; y la de los valores para Pext &#40;15&#46;8 mmHg&#41; se asociaron con&#58; hipoxemia&#47; disminuci&#243;n de la presi&#243;n venosa mezclada del O2&#44; as&#237; como con anormalidades de la mec&#225;nica pulmonar&#46; Condiciones hemodin&#225;micas que no se modificaron para la Sp &#40;5&#46;47&#59; 95&#37; IC&#58; 3&#46;64 - 7&#46;3 mmHg&#47;L min&#47;m2&#44; p &#61; 0&#46;4&#41; y la Pext &#40;15&#46;7 mmHg&#44; p &#61; 0&#46;2&#41;&#59; sin embargo&#44; s&#237; se vieron asociadas a una disminuci&#243;n significativa en paralelo de la PAPm&#47;IC durante la AAO2 99&#46;5&#37;&#46; Observaciones hemodin&#225;micas que para la cohorte A&#44; se caracterizaron por una reducci&#243;n de la PAPm promedio &#40;12&#46;3 mmHg&#44; p &#60;0 004 por una disminución de la sp 6 02 95 ci: 4 04 - 8 a 3 11 49 mmhg l min m2 p &#60;0 008 y por el descenso de pext 8 58 plusmn 3 a 4 7 1 mmhg p &#60;0 01 al compararse con las documentadas raa en cambio para la cohorte b papm promedio y ic no se modificaron sp mostró sólo tendencia a disminuir p pext aumento de 12 plusmn 2 9 20 6 4 mmhg &#60;0 03 en relación a las registradas raa bajo la aao2 - 99 5 se observaron diferencias significativas para papm ic 95 su localización promedio a: 19 plusmn 6 vs b: 41 2 11 mmhg p &#60;0 001 y pext a: 4 7 plusmn 1 vs b: 20 6 9 mmhg p &#60;0 001 y sin cambios en la sp entre cohorte a b conclusiones: cuando se analiza papm ic obtiene información que es valiosa para interpretar resistencia vascular pulmonar linear sujetos con epoc e hp embargo las anormalidades de no necesariamente reflejan aumento exclusivo arteriolar acuerdo observaciones agudas este estudio posiblemente solo sea esperarse beneficio oxigenoterapia largo plazo sobre circulación post-carga del ventrículo derecho aquellos portadores el reposo <30 mmhg</30>      "
      ]
      "en" => array:1 [
        "resumen" => "Objectives&#58; We sought to analyze exercise-derived mean pulmonary artery pressure &#40;Mpap&#41; - cardiac index &#40;CI&#41; - relationship to expand the concepts regarding its nature and to better identify pulmonary hemodynamic responders to acute oxygen breathing &#40;AOB - 99&#46;5&#37;&#41; in pulmonary hypertension &#40;PH&#41; - COPD patients&#46; Methods&#58; mPAP&#47;CI and extrapolated pressure &#40;Pext&#41; to zero flow were obtained breathing room air &#40;BRA&#41; and under AOB - 99&#46;5&#37; in 40 stable COPD patients with rest and exercise PH&#46; Hemodynamic characteristics were analyzed for the entire cohort and separate for cases those with resting &#60; or &#62; 30 mmHg mPAP &#40;cohort - A and B&#44; respectively&#41;&#46; Results&#58; mPAP&#47;CI abnormal location&#44; slope &#40;Sp&#58; 5&#46;77&#59; 95&#37; CI&#58; 5&#46;02 - 6&#46;52 mmHg&#47;L min&#47;m2&#41; and Pext values &#40;15&#46;8 mmHg&#41; were associated with hypoxemia&#47;decreased mixed venous - PO2 and lung mechanics abnormalities&#46; Hemodynamic conditions that did not change for Sp &#40;5&#46;47&#59; 95&#37; CI&#58; 3&#46;64 - 7&#46;3 mmHg&#47;L min&#47;m2&#44; p &#61; 0&#46;4&#41; and Pext &#40;15&#46;7 mmHg&#44; p &#61; 0&#46;2&#41; associated with a mPAP&#47;CI significantly decrease in parallel during AOB - 99&#46;5&#37;&#46; For cohort - A&#44; an average-mPAP decline &#40;12&#46;3 mmHg&#44; p &#60;0 004 associated with a slope decrease from 6 02 95 ci: 4 04 - 8 to 3 11 49 mmhg l min m2 p &#60;0 008 mpap ci - 95 down-ward displacement and pext decrease from 8 58 plusmn 3 to 4 7 1 mmhg p &#60;0 01 in relation to bra were observed for cohort-b average-mpap and mpap ci - 95 location did not change sp show a trend decrease p pext significantly increase from 12 plusmn 2 9 20 6 4 mmhg &#60;0 03 in relation to bra under aob - 99 5 significant differences for mpap ci 95 location average-mpap a: 19 plusmn 6 vs b: 41 2 11 mmhg p &#60;0 001 and pext a: 4 7 plusmn 1 vs b: 20 6 9 mmhg p &#60;0 001 without sp change between cohorts a and b were documented conclusions: when exercise derived mpap ci is analyzed valuable information for linear-pulmonary vascular resistance - lpvr could be obtained ph copd patients abnormalities not always reflect pure arteriolar increased all ph-copd hemodynamic benefit on the pulmonary circulation right ventricular afterload expected with long-term oxygen therapy in resting <30 mmhg mpap-ph-copd patients</30>      "
      ]
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          "en" => "0028657fig3&#46;jpg&#34; width&#61;&#34;1025&#34; height&#61;&#34;812&#34; alt&#61;&#34;Table 3&#46; mPAP&#47;CI and Pext results breath"
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          "en" => "028657fig4&#46;jpg&#34; width&#61;&#34;1050&#34; height&#61;&#34;1100&#34; alt&#61;&#34;Figure 1&#46; PH-COPD patients showed an abnormal mPAP&#47;CI &#40;linear PVR&#41; location&#44; slope and Pext when compared to normal subjects &#40;in black&#41;&#46; A significant decrease in parallel for the mPAP&#47;CI &#40;without a slope change&#41; and without Pex"
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          "en" => "0028657fig5&#46;jpg&#34; width&#61;&#34;2008&#34; height&#61;&#34;750&#34; alt&#61;&#34;Table 4&#46; mPAP&#47;CI and Pext results breathing room air and FiO2 99&#46;5"
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          "en" => "A non-significant decrease linear PVR is documented for COPD patients with a resting mPAP &#62;30 mmHg during 99&#46;5&#37; oxygen breathing &#40;in gray&#41;&#46; On the contrary&#44; for those with a resting mPAP &#60;30 mmHg&#44; a significant decrease for linear PVR was observed &#40;in gray&#41;&#46; Therefore&#44; RV hemodynamic benefit on afterload could be predicted for LTOT only for COPD patients with a resting mPAP of &#60;30 mmHg&#46;"
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          "en" => "Comparison of normal individuals and COPD patients and between COPD patients without resting or exercising PH &#40;Group - I&#41;&#44; with those without resting with exercising PH &#40;Group - II&#41; and with resting and exercising PH &#40;Group - III&#41; and between group III COPD collected from the literature and the studied PH - COPD patients&#46;"
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          "en" => "0028657fig8&#46;jpg&#34; width&#61;&#34;1029&#34; height&#61;&#34;908&#34; alt&#61;&#34;Figure 3&#46; It could be seen a progressive and significant mPAP&#47;CI -95&#37; CI up-ward location for Group I in relation to normal subjects&#44; for Group II in relation to Group I&#44; and for Group III in relation to Group II COPD patients&#46; No differences between Groups III &#40;from the literature &#40;in gray&#41; and our"
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Article information

ISSN: 14059940
Original language: English

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Year/Month	Html	Pdf	Total

2024 November	3	0	3
2024 October	18	11	29
2024 September	40	20	60
2024 August	18	15	33
2024 July	20	9	29
2024 June	17	5	22
2024 May	10	3	13
2024 April	16	5	21
2024 March	15	12	27
2024 February	21	6	27
2024 January	21	2	23
2023 December	17	7	24
2023 November	29	7	36
2023 October	10	9	19
2023 September	9	5	14
2023 August	6	4	10
2023 July	6	3	9
2023 June	7	4	11
2023 May	14	14	28
2023 April	17	2	19
2023 March	6	1	7
2023 February	18	5	23
2023 January	16	7	23
2022 December	11	5	16
2022 November	23	8	31
2022 October	14	9	23
2022 September	15	5	20
2022 August	11	7	18
2022 July	16	4	20
2022 June	12	8	20
2022 May	20	6	26
2022 April	32	16	48
2022 March	12	8	20
2022 February	20	4	24
2022 January	16	9	25
2021 December	9	12	21
2021 November	15	18	33
2021 October	22	11	33
2021 September	16	9	25
2021 August	15	6	21
2021 July	6	11	17
2021 June	15	5	20
2021 May	14	8	22
2021 April	76	17	93
2021 March	31	5	36
2021 February	31	5	36
2021 January	28	16	44
2020 December	15	7	22
2020 November	22	11	33
2020 October	21	6	27
2020 September	10	5	15
2020 August	19	9	28
2020 July	17	12	29
2020 June	20	8	28
2020 May	19	3	22
2020 April	16	7	23
2020 March	8	2	10
2020 February	21	7	28
2020 January	15	5	20
2019 December	15	7	22
2019 November	22	7	29
2019 October	17	2	19
2019 September	14	10	24
2019 August	12	3	15
2019 July	17	14	31
2019 June	42	9	51
2019 May	96	21	117
2019 April	53	0	53
2019 March	4	3	7
2019 February	6	5	11
2019 January	3	1	4
2018 December	3	1	4
2018 November	4	3	7
2018 October	11	8	19
2018 September	25	10	35
2018 August	9	0	9
2018 July	10	1	11
2018 June	9	6	15
2018 May	4	5	9
2018 April	11	10	21
2018 March	5	0	5
2018 February	6	0	6
2018 January	2	1	3
2017 December	11	0	11
2017 November	8	0	8
2017 October	15	0	15
2017 September	7	2	9
2017 August	10	4	14
2017 July	8	3	11
2017 June	20	7	27
2017 May	20	1	21
2017 April	15	2	17
2017 March	22	35	57
2017 February	34	5	39
2017 January	11	1	12
2016 December	12	2	14
2016 November	18	1	19
2016 October	24	2	26
2016 September	15	1	16
2016 August	13	0	13
2016 July	12	3	15
2016 June	42	6	48
2016 May	36	11	47
2016 April	32	12	44
2016 March	29	13	42
2016 February	32	18	50
2016 January	21	12	33
2015 December	27	11	38
2015 November	21	11	32
2015 October	31	15	46
2015 September	28	4	32
2015 August	42	4	46
2015 July	38	7	45
2015 June	27	0	27
2015 May	24	2	26
2015 April	39	6	45
2015 March	20	9	29
2015 February	22	2	24
2015 January	35	5	40
2014 December	56	4	60
2014 November	43	4	47
2014 October	44	3	47
2014 September	50	1	51
2014 August	30	3	33
2014 July	31	3	34
2014 June	32	3	35
2014 May	32	3	35
2014 April	27	0	27
2014 March	54	13	67
2014 February	53	8	61
2014 January	30	8	38
2013 December	52	6	58
2013 November	38	8	46
2013 October	43	9	52
2013 September	42	8	50
2013 August	53	6	59
2013 July	41	4	45
2013 June	21	6	27
2013 May	13	3	16
2013 April	16	13	29
2013 March	24	7	31
2013 February	14	6	20
2013 January	9	3	12
2012 December	10	2	12
2012 November	4	4	8
2012 October	9	2	11
2012 September	2	1	3
2011 June	562	0	562

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