RESUMO

Electrophysiological alterations of the myocardium caused by acute ischemia constitute a pro-arrhythmic substrate for the generation of potentially lethal arrhythmias. Experimental evidence has shown that the main components of acute ischemia that induce these electrophysiological alterations are hyperkalemia, hypoxia (or anoxia in complete artery occlusion), and acidosis. However, the influence of each ischemic component on the likelihood of reentry is not completely established. Moreover, the role of the His-Purkinje system (HPS) in the initiation and maintenance of arrhythmias is not completely understood. In the present work, we investigate how the three components of ischemia affect the vulnerable window (VW) for reentry using computational simulations. In addition, we analyze the role of the HPS on arrhythmogenesis. A 3D biventricular/torso human model that includes a realistic geometry of the central and border ischemic zones with one of the most electrophysiologically detailed model of ischemia to date, as well as a realistic cardiac conduction system, were used to assess the VW for reentry. Four scenarios of ischemic severity corresponding to different minutes after coronary artery occlusion were simulated. Our results suggest that ischemic severity plays an important role in the generation of reentries. Indeed, this is the first 3D simulation study to show that ventricular arrhythmias could be generated under moderate ischemic conditions, but not in mild and severe ischemia. Moreover, our results show that anoxia is the ischemic component with the most significant effect on the width of the VW. Thus, a change in the level of anoxia from moderate to severe leads to a greater increment in the VW (40 ms), in comparison with the increment of 20 ms and 35 ms produced by the individual change in the level of hyperkalemia and acidosis, respectively. Finally, the HPS was a necessary element for the generation of approximately 17% of reentries obtained. The retrograde conduction from the myocardium to HPS in the ischemic region, conduction blocks in discrete sections of the HPS, and the degree of ischemia affecting Purkinje cells, are suggested as mechanisms that favor the generation of ventricular arrhythmias.

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RESUMO

AIMS: This computational modelling work illustrates the influence of hyperkalaemia and electrical uncoupling induced by defined ischaemia on action potential (AP) propagation and the incidence of reentry at the Purkinje-ventricle interface in mammalian hearts. METHODS AND RESULTS: Unidimensional and bidimensional models of the Purkinje-ventricle subsystem, including ischaemic conditions (defined as phase 1B) in the ventricle and an ischaemic border zone, were developed by altering several important electrophysiological parameters of the Luo-Rudy AP model of the ventricular myocyte. Purkinje electrical activity was modelled using the equations of DiFrancesco and Noble. Our study suggests that an extracellular potassium concentration [K(+)]o >14 mM and a slight decrease in intercellular coupling induced by ischaemia in ventricle can cause conduction block from Purkinje to ventricle. Under these conditions, propagation from ventricle to Purkinje is possible. Thus, unidirectional block (UDB) and reentry can result. When conditions of UDB are met, retrograde propagation with a long delay (320 ms) may re-excite Purkinje cells, and give rise to a reentrant pathway. This induced reentry may be the origin of arrhythmias observed in phase 1B ischaemia. CONCLUSION: In a defined setting of ischaemia (phase 1B), a small amount of uncoupling between ventricular cells, as well as between Purkinje and ventricular tissue, may induce UDBs and reentry. Hyperkalaemia is also confirmed to be an important factor in the genesis of reentrant rhythms, since it regulates the range of coupling in which UDBs may be induced.

Assuntos

RESUMO

Las arritmias ventriculares usualmente se presentan como consecuencia de isquemia miocárdica aguda, lo cual causa la mayoría de las muertes súbitas. La heterogeneidad cardiaca tanto funcional (diferente comportamiento eléctrico en los miocitos) como bioquímica (diferentes concentraciones iónicas en isquemia), altera el comportamiento eléctrico del ventrículo y genera dispersión en la repolarización del potencial de acción, por lo que se convierte en sustrato funcional para la generación de arritmias fatales. En este trabajo se revisan las técnicas experimentales para el estudio y la detección de arritmias por reentrada, y se valida un modelo geométrico de isquemia, en presencia de heterogeneidad eléctrica en la región transmural de la pared ventricular. Para ello se utilizaron simulaciones bidimensionales de un modelo biofísicamente detallado y se obtuvieron reentradas lobulares en diferentes configuraciones de las células M de la pared ventricular.

Ventricular arrhythmias usually appear as consequence of acute myocardial ischemia, responsible for most of sudden deaths. Functional (different electrical behavior of myocytes) as well as biochemical (different ionic concentrations during ischemia) cardiac heterogeneity alter the ventricle electric performance and generate dispersion in the action potential repolarization that turns into functional substrate for the generation of fatal arrhythmias. In this work the experimental techniques for the study and detection of arrhythmias by re-entry are reviewed and a geometrical model of ischemia is validated in the presence of electrical heterogeneity in the trans-mural region of the ventricular wall. For this purpose, bi-dimensional simulations of a detailed biophysical model were used and lobular re-entries in different configurations of the M cells of the ventricular wall were obtained.

Assuntos