Article information
La fibrilación ventricular, la isquemia miocárdica y la muerte súbita son fisiopatologías cardiacas inseparables. La influencia de la distribución de células del medio miocardio en la formación de arritmias en la pared heterogénea cardiaca en presencia de isquemia sub-epicárdica, no está del todo dilucidada. En este estudio se modela una porción plana de la pared transmural con diferentes configuraciones de células del medio miocardio que se adjuntan a las heterogeneidades bioquímicas presentes en isquemia sub-epicárdica para cuantificar su influencia en la formación de arritmias.
Se obtuvieron reentradas lobulares no sostenidas en torno de la lesión isquémica que interfieren con las células M, alterando la repolarización del tejido. La función de vulnerabilidad que cuantifica la prospección a reentradas es aproximada por una función logística, y su mayor expresión ocurre en el minuto 8,75 de isquemia modelada.
La heterogeneidad bioquímica y morfológica en el tejido virtual estudiado dan como resultado una arritmia por reentrada; su secuela en la vulnerabilidad del tejido aumenta a medida que crece la severidad de la hiperkalemia. Los electrogramas obtenidos muestran depresión TQ y elevación ST con una morfología de taquicardia ventricular polimórfica.
Palabras clave:
células M
electrogramas
función de vulnerabilidad
isquemia sub-epicárdica
modelo de Luo-Rudy
reentrada transmural
taquicardia polimórfica
Ventricular fibrillation, myocardial ischemia and sudden cardiac death are inseparable cardiac pathophysiologies. The influence of the distribution of myocardial cells in the formation of arrhythmias in the heterogeneous cardiac wall in the presence of sub-epicardial ischemia is not entirely elucidated. This study models a flat portion of the transmural wall under different myocardial cell configurations attached to the biochemical heterogeneity present in sub-epicardial ischemia to quantify their influence on the development of arrhythmias.
Lobular non-sustained reentries were obtained around the ischemic lesion that interfere with M cells, altering the tissue repolarization. Vulnerability function that quantifies prospection to reentries is approximated by a logistic function, and its main expression occurs in 8.75 minutes of modeled ischemia.
The biochemical and morphological heterogeneity in the virtual tissue studied results in a reentrant arrhythmia; its sequel to the tissue vulnerability increases as the severity of hyperkalemia grows. Electrograms obtained show TQ depression and ST elevation with a morphology of polymorphic ventricular tachycardia.
Key words:
M cells
electrograms
vulnerability function
sub-epicardial ischemia
Luo-Rudy model
transmural reentry
polymorphic tachycardia
Full text is only aviable in PDF
Bibliografía
[1.]
C. Antzelevitch, S. Sicouri, S.H. Litovsky, et al.
Heterogeneity within the ventricular wall. Electrophysiology and pharmacology of epicardial, endocardial, and M cells.
Circ Res, 69 (1991), pp. 1427-1449
[2.]
S.H. Litovsky, C. Antzelevitch.
Transient outward current prominent in canine ventricular epicardium but not endocardium.
Circ Res, 62 (1988), pp. 116-126
[3.]
S. Sicouri, C. Antzelevitch.
A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle.
The M cell. Circ Res, 68 (1991), pp. 1729-1741
[4.]
C. Antzelevitch.
Modulation of transmural repolarization.
Ann N Y Acad Sci, 1047 (2005), pp. 314-323
[5.]
D.W. Liu, G.A. Gintant, C. Antzelevitch.
Ionic bases for electrophysiological distinctions among epicardial, midmyocardial, and endocardial myocytes from the free wall of the canine left ventricle.
Circ Res, 72 (1993), pp. 671-687
[6.]
G.X. Yan, R.S. Lankipalli, J.F. Burke, S. Musco, P.R. Kowey.
Ventricular repolarization components on the electrocardiogram: cellular basis and clinical significance.
J Am Coll Cardiol, 42 (2003), pp. 401-409
[7.]
K. Gima, Y. Rudy.
Ionic current basis of electrocardiographic waveforms: a model study.
Circ Res, 90 (2002), pp. 889-896
[8.]
C. Antzelevitch.
Heterogeneity and cardiac arrhythmias: an overview.
Heart Rhythm, 4 (2007), pp. 964-972
[9.]
C. Antzelevitch.
Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes.
Am J Physiol Heart Circ Physiol, 293 (2007), pp. H2024-H2038
[10.]
S. Atar, A. Barbagelata, Y. Birnbaum.
Electrocardiographic diagnosis of ST-elevation myocardial infarction.
Cardiol Clin, 24 (2006), pp. 343-365
[11.]
C. Antzelevitch, J. Fish.
Electrical heterogeneity within the ventricular wall.
Basic Res Cardiol, 96 (2001), pp. 517-527
[12.]
C. Antzelevitch.
Cardiac repolarization.
The long and short of it. Europace, 7 (2005), pp. 3-9
[13.]
R. Coronel, J.W. Fiolet, F.J. Wilms-Schopman, et al.
Distribution of extracellular potassium and its relation to electrophysiologic changes during acute myocardial ischemia in the isolated perfused porcine heart.
Circulation, 77 (1988), pp. 1125-1138
[14.]
M.J. Janse, J. Cinca, H. Morena, et al.
The “border zone” in myocardial ischemia.
An electrophysiological, metabolic, and histochemical correlation in the pig heart. Circ Res, 44 (1979), pp. 576-588
[15.]
H. Morena, M.J. Janse, J.W. Fiolet, et al.
Comparison of the effects of regional ischemia, hypoxia, hyperkalemia, and acidosis on intracellular and extracellular potentials and metabolism in the isolated porcine heart.
Circ Res, 46 (1980), pp. 634-646
[16.]
W.E. Cascio, T.A. Johnson, L.S. Gettes.
Electrophysiologic changes in ischemic ventricular myocardium: I. Influence of ionic, metabolic, and energetic changes.
J Cardiovasc Electrophysiol, 6 (1995), pp. 1039-1062
[17.]
A.A. Wilde, A.G. Kleber.
The combined effects of hypoxia, high K+, and acidosis on the intracellular sodium activity and resting potential in guinea pig papillary muscle.
Circ Res, 58 (1986), pp. 249-256
[18.]
A.A. Wilde, G. Aksnes.
Myocardial potassium loss and cell depolarisation in ischaemia and hypoxia.
Cardiovasc Res, 29 (1995), pp. 1-15
[19.]
M.J. Janse, A.L. Wit.
Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction.
Physiol Rev, 69 (1989), pp. 1049-1169
[20.]
E. Carmeliet.
Cardiac ionic currents and acute ischemia: from channels to arrhythmias.
Physiol Rev, 79 (1999), pp. 917-1017
[21.]
J.M. Ferrero Jr., J. Saiz, J.M. Ferrero, N.V. Thakor.
Simulation of action potentials from metabolically impaired cardiac myocytes. Role of ATP-sensitive K+ current.
Circ Res, 79 (1996), pp. 208-221
[22.]
R. Dumaine, J.A. Towbin, P. Brugada, et al.
Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent.
Circ Res, 85 (1999), pp. 803-809
[23.]
P.C. Viswanathan, R.M. Shaw, Y. Rudy.
Effects of IKr and IKs heterogeneity on action potential duration and its rate dependence: a simulation study.
Circulation, 99 (1999), pp. 2466-2474
[24.]
A.G. Kleber, M.J. Janse, F.J. Wilms-Schopmann, A.A. Wilde, R. Coronel.
Changes in conduction velocity during acute ischemia in ventricular myocardium of the isolated porcine heart.
Circulation, 73 (1986), pp. 189-198
[25.]
W.E. Cascio.
Myocardial ischemia: what factors determine arrhythmogenesis?.
J Cardiovasc Electrophysiol, 12 (2001), pp. 726-729
[26.]
G.M. Faber, Y. Rudy.
Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study.
Biophys J, 78 (2000), pp. 2392-2404
[27.]
C.H. Luo, Y. Rudy.
A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes.
Circ Res, 74 (1994), pp. 1071-1096
[28.]
Y. Rudy, J.R. Silva.
Computational biology in the study of cardiac ion channels and cell electrophysiology.
Q Rev Biophys, 39 (2006), pp. 57-116
[29.]
A.L. Hodgkin, A.F. Huxley.
A quantitative description of membrane current and its application to conduction and excitation in nerve.
J Physiol, 117 (1952), pp. 500-544
[30.]
S. Weidmann.
Electrical constants of trabecular muscle from mammalian heart.
J Physiol, 210 (1970), pp. 1041-1054
[31.]
H.J. Jongsma, R. Wilders.
Gap junctions in cardiovascular disease.
Circ Res, 86 (2000), pp. 1193-1197
[32.]
A.G. Kleber, Y. Rudy.
Basic mechanisms of cardiac impulse propagation and associated arrhythmias.
Physiol Rev, 84 (2004), pp. 431-488
[33.]
J. Beaumont, N. Davidenko, J.M. Davidenko, J. Jalife.
Spiral waves in two-dimensional models of ventricular muscle: formation of a stationary core.
Biophys J, 75 (1998), pp. 1-14
[34.]
R. Coronel.
Heterogeneity in extracellular potassium concentration during early myocardial ischaemia and reperfusion: implications for arrhythmogenesis.
Cardiovasc Res, 28 (1994), pp. 770-777
[35.]
J.M. Ferrero Jr., B. Trenor, B. Rodríguez, J. Sáiz.
Electrical activity and reentry during acute regional myocardial ischemia: insights from simulations.
Int J Bifurcation and Chaos, 13 (2003), pp. 3703-3715
[36.]
D.W. Liu, C. Antzelevitch.
Characteristics of the delayed rectifier current (IKr and IKs) in canine ventricular epicardial, midmyocardial, and endocardial myocytes. A weaker IKs contributes to the longer action potential of the M cell.
Circ Res, 76 (1995), pp. 351-365
[37.]
R.H. Clayton, A.V. Holden.
Propagation of normal beats and re-entry in a computational model of ventricular cardiac tissue with regional differences in action potential shape and duration.
Prog Biophys Mol Biol, 85 (2004), pp. 473-499
[38.]
F.G. Akar, G.X. Yan, C. Antzelevitch, D.S. Rosenbaum.
Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome.
Circulation, 105 (2002), pp. 1247-1253
[39.]
S. Poelzing, D.S. Rosenbaum.
Nature, significance, and mechanisms of electrical heterogeneities in ventricle.
Anat Rec A Discov Mol Cell Evol Biol, 280 (2004), pp. 1010-1017
[40.]
O. Henao, J.M. Ferrero, E. Ramírez, J. Sáiz.
Arritmias cardiacas generadas por heterogeneidad electrofisiológica: estudio mediante simulación.
Rev Colomb Cardiol, 14 (2007), pp. 185-197
[41.]
D.B. Geselowitz.
On the theory of the electrocardiogram.
Proceedings of the IEEE, 77 (1989), pp. 857-876
[42.]
J. Saiz, J.M. Ferrero Jr., M. Monserrat, J.M. Ferrero, N.V. Thakor.
Influence of electrical coupling on early afterdepolarizations in ventricular myocytes.
IEEE Trans Biomed Eng, 46 (1999), pp. 138-147
[43.]
A.T. Winfree.
On measuring curvature and electrical diffusion coefficients in anisotropic myocardium: comments on “effects of bipolar point and line simulation in anisotropic rabbit epicardium: assessment of the critical radius of curvature for longitudinal block”.
IEEE Trans Biomed Eng, 43 (1996), pp. 1200-1203
[44.]
A.T. Winfree.
Electrical singular filaments in the heart wall.
The Geometry of Biological Time,, 2nd, pp. 455-526
[45.]
V.Y. Sidorov, R.R. Aliev, M.C. Woods, et al.
Spatiotemporal dynamics of damped propagation in excitable cardiac tissue.
Phys Rev Lett, 91 (2003), pp. 208104
[46.]
A.T. Winfree.
Heart muscle as a reaction-diffusion medium: The roles of electric potential diffusion, activation front curvature, and anisotropy.
Int J Bifurcation and Chaos, 7 (1997), pp. 487-526
[47.]
V.G. Fast, A.G. Kleber.
Role of wavefront curvature in propagation of cardiac impulse.
Cardiovasc Res, 33 (1997), pp. 258-271
[48.]
L.S. Gettes, W.E. Cascio.
Effect of acute ischemia on cardiac electrophysiology.
The Heart and Cardiovascular System, pp. 2021-2053
[49.]
M.R. Franz, M. Zabel.
Electrophysiological basis of QT dispersion measurements.
Prog Cardiovasc Dis, 42 (2000), pp. 311-324
[50.]
F.L. Burton, S.M. Cobbe.
Dispersion of ventricular repolarization and refractory period.
Cardiovasc Res, 50 (2001), pp. 10-23
[51.]
M. Restivo, W.B. Gough, N. El-Sherif.
Ventricular arrhythmias in the subacute myocardial infarction period. High-resolution activation and refractory patterns of reentrant rhythms.
Circ Res, 66 (1990), pp. 1310-1327
[52.]
T. Osaka, I. Kodama, N. Tsuboi, J. Toyama, K. Yamada.
Effects of activation sequence and anisotropic cellular geometry on the repolarization phase of action potential of dog ventricular muscles.
Circulation, 76 (1987), pp. 226-236
[53.]
M. Restivo, E.B. Caref, D.O. Kozhevnikov, N. El-Sherif.
Spatial dispersion of repolarization is a key factor in the arrhythmogenicity of long QT syndrome.
J Cardiovasc Electrophysiol, 15 (2004), pp. 323-331
[54.]
F.G. Akar, G.X. Yan, C. Antzelevitch, D.S. Rosenbaum.
Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome.
Circulation, 105 (2002), pp. 1247-1253
[55.]
G.X. Yan, W. Shimizu, C. Antzelevitch.
Characteristics and distribution of M cells in arterially perfused canine left ventricular wedge preparations.
Circulation, 98 (1998), pp. 1921-1927
[56.]
N. Gaborit, S. Le Bouter, V. Szuts, et al.
Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart.
J Physiol, 582 (2007), pp. 675-693
[57.]
E. Soltysinska, S. Olesen, T. Christ, et al.
Transmural expression of ion channels and transporters in human nondiseased and end-stage failing hearts.
Pflugers Archiv Eur J Physiol, 459 (2009), pp. 11-23
[58.]
C. Antzelevitch, W. Shimizu, G.X. Yan, et al.
The M cell: Its contribution to the ECG and to normal and abnormal electrical function of the heart.
J Cardiovasc Electrophysiol, 10 (1999), pp. 1124-1152
[59.]
C. Antzelevitch.
Cellular basis for the repolarization waves of the ECG.
Ann N Y Acad Sci, 1080 (2006), pp. 268-281
[61.]
M.J. Janse.
ST-segment elevation or TQ-segment depression?.
Heart Rhythm, 4 (2007), pp. 207
[62.]
A. Glukhov, V. Fedorov, Q. Lou, et al.
Transmural dispersion of repolarization in failing and nonfailing human ventricle.
Circ Res, 106 (2010), pp. 981-991
[63.]
A. Burashnikov, C. Antzelevitch.
Prominent I(Ks) in epicardium and endocardium contributes to development of transmural dispersion of repolarization but protects against development of early afterdepolarizations.
J Cardiovasc Electrophysiol, 13 (2002), pp. 172-177
[64.]
A.G. Kleber.
Resting membrane potential, extracellular potassium activity, and intracellular sodium activity during acute global ischemia in isolated perfused guinea pig hearts.
Circ Res, 52 (1983), pp. 442-450
[65.]
A.G. Kleber, M.J. Janse, F.J. Wilms-Schopmann, A.A. Wilde, R. Coronel.
Changes in conduction velocity during acute ischemia in ventricular myocardium of the isolated porcine heart.
Circulation, 73 (1986), pp. 189-198
[66.]
B.M. Tice, B. Rodríguez, J. Eason, N. Trayanova.
Mechanistic investigation into the arrhythmogenic role of transmural heterogeneities in regional ischaemia phase 1A.
Europace, 9 (2007), pp. VI46-VI58
[67.]
R. Coronel, F.J. Wilms-Schopman, L.R. Dekker, M.J. Janse.
Heterogeneities in [K+] o and TQ potential and the inducibility of ventricular fibrillation during acute regional ischemia in the isolated perfused porcine heart.
Circulation, 92 (1995), pp. 120-129
[68.]
X. Wan, S.M. Bryant, G. Hart.
The effects of [K+]o on regional differences in electrical characteristics of ventricular myocytes in guinea-pig.
Exp. Physiol, 85 (2000), pp. 769-774
[69.]
N. Gronich, A. Kumar, Y. Zhang, I. Efimov, N. Soldatov.
Molecular remodeling of ion channels, exchangers and pumps in atrial and ventricular myocytes in ischemic cardiomyopathy.
Channels, 4 (2010), pp. 1-7
[70.]
Y. Kagiyama, J.L. Hill, L.S. Gettes.
Interaction of acidosis and increased extracellular potassium on action potential characteristics and conduction in guinea pig ventricular muscle.
Circ Res, 51 (1982), pp. 614-623
[71.]
J. Jalife, O. Berenfeld.
Molecular mechanisms and global dynamics of fibrillation: an integrative approach to the underlying basis of vortex-like reentry.
J Theor Biol, 230 (2004), pp. 475-487
[72.]
J. Ferrero Jr., V. Torres, F. Montilla, E. Colomar.
Simulation of reentry during acute myocardial ischemia: role of ATP-sensitive potassium current and acidosis.
Computers in Cardiology, 27 (2000), pp. 239-242
[73.]
C.A. Remme, A.A. Wilde.
KATP channel openers, myocardial ischemia, and arrhythmias -should the electrophysiologist worry?.
Cardiovasc. Drugs Ther, 14 (2000), pp. 17-22
[74.]
P. Taggart, D.M. Yellon.
Preconditioning and arrhythmias.
Circulation, 106 (2002), pp. 2999-3001
[75.]
G.X. Yan, K.A. Yamada, A.G. Kleber, J. McHowat, P.B. Corr.
Dissociation between cellular K+ loss, reduction in repolarization time, and tissue ATP levels during myocardial hypoxia and ischemia.
Circ Res, 72 (1993), pp. 560-570
[76.]
B. Trenor, L. Romero, J.M. Ferrero Jr., et al.
Vulnerability to reentry in a regionally ischemic tissue: a simulation study.
Ann Biomed Eng, 35 (2007), pp. 1756-1770
[77.]
P. Taggart, P.M. Sutton, T. Opthof, et al.
Transmural repolarisation in the left ventricle in humans during normoxia and ischaemia.
Cardiovasc Res, 50 (2001), pp. 454-462
[78.]
P.M.I. Sutton, P. Taggart, T. Opthof, et al.
Repolarisation and refractoriness during early ischaemia in humans.
Heart, 84 (2000), pp. 365-369
[79.]
R.M. Donaldson, F.S. Nashat, D. Noble, P. Taggart.
Differential effects of ischaemia and hyperkalaemia on myocardial repolarization and conduction times in the dog.
J Physiol, 353 (1984), pp. 393-403
[80.]
J.N. Weiss, N. Venkatesh, S.T. Lamp.
ATP-sensitive K+ channels and cellular K+loss in hypoxic and ischaemic mammalian ventricle.
J Physiol, 447 (1992), pp. 649-673
[81.]
M.J. Janse, F.J. van Capelle, H. Morsink, et al.
Flow of “injury” current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts. Evidence for two different arrhythmogenic mechanisms.
Circ Res, 47 (1980), pp. 151-165
[82.]
A. Glukhov, T. Flagg, V. Fedorov, I. Efimov, C. Nichols.
Differential KATP channel pharmacology in intact mouse heart.
J Molec Cell Cardiol, 48 (2010), pp. 152-160
[83.]
J. Keener.
A mathematical model for the vulnerable phase in myocardium.
Mathematical Biosciences, 90 (1988), pp. 3-18
[84.]
A.T. Winfree.
Electrical instability in cardiac muscle: phase singularities and rotors.
J Theor Biol, 138 (1989), pp. 353-405
[85.]
K.R. Laurita, S.D. Girouard, F.G. Akar, D.S. Rosenbaum.
Modulated dispersion explains changes in arrhythmia vulnerability during premature stimulation of the heart.
Circulation, 98 (1998), pp. 2774-2780
[86.]
X. Wan, K.R. Laurita, E.J. Pruvot, D.S. Rosenbaum.
Molecular correlates of repolarization alternans in cardiac myocytes.
J Mol Cell Cardiol, 39 (2005), pp. 419-428
Copyright © 2011. Sociedad Colombiana de Cardiología y Cirugía Cardiovascular