| Sudden cardiac death (SCD) is a leading cause of death in the United States, resulting in 325,000 deaths per annum. A sizeable majority of SCD cases are preceded by ventricular tachyarrhythmias that are commonly terminated in medical practice with defibrillators. Nevertheless, several instances of defibrillation failure have been documented in both medical and physiological investigations. This dissertation is devoted to investigating tachycardia-induced early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs), in the presence of intracellular calcium (Ca) accumulation, as possible reasons for defibrillation failure.;Accomplishing this investigation required utilization of a bidomain representation of cardiac tissue consisting of cardiomyocyte AP models with developed intracellular Ca dynamics, using parallel supercomputer resources. In order to reduce overall computation time, a novel parallelized multigrid method was developed.;Incorporating the specific characteristics of the AP model (such as electroporation, Ca alternans, and various formulations of spontaneous Ca release), significantly expanded the possibilities of the proposed model.;The presented studies showed that clusters of EADs and DADs were found to affect defibrillation outcomes by preventing immediate electrical quiescence of the cardiac tissue. Indeed, a transient period of tachyarrhythmic electrical activity was observed following the shock and eventually subsided after a time interval less than several seconds. In this scenario, these clusters introduce electrical heterogeneity in the cardiac tissue that is encountered by waves generated by normal cardiac pacemaker system function, which can either prolong the transient tachyarrhythmia or produce frank defibrillation failure.;In summary, our findings show that intracellular Ca dynamics, via clusters of EADs and DADs, can facilitate the appearance of defibrillation failure as a result of an interaction with subsequent pacemaker-generated excitation waves. This gives insights into the preconditions for these events to occur and possible therapeutic interventions to address these scenarios. |
