Long-lasting AC stimulation of myocardial tissue

Fibrillation, the life-threatening loss of cardiac output that occurs through a severe disruption in the normal propagation of the electrical wavefront responsible for triggering regular contraction of the heart, is treated through timely delivery of strong electrical shocks, termed defibrillation. While the clinical procedure is performed with direct current (DC) waveforms, recent experimental studies have shown that long-lasting alternating current (AC) waveforms can defibrillate the heart via novel mechanisms, such as entrainment and sustained depolarization. The purpose of this research is, through the use of computational models, to explore the mechanisms by which long-lasting AC shocks affect cardiac tissue and elucidate the role of entrainment and sustained depolarization in defibrillation.; The first phase of the study explores the affects of long-lasting AC stimuli on cardiac tissue in diastole (at rest), which insures that the tissue response is not obscured by the pre-shock state of the myocardium. Simulations are performed using models of single cardiac cells and sections of myocardial tissue, to determine important mechanisms at both the cell membrane and multicellular level. Entrainment and sustained depolarization are observed on both spatial levels; these responses are effected through both the simultaneous activation and resetting of individual ionic membrane channels, and the interaction between the regions of shock-induced virtual electrode polarization (VEP) during the shock. The conditions that give rise to various types of phase-locking of the transmembrane potential to the stimulus are also explored.; The second phase of the study focuses on the role that entrainment and sustained depolarization play in defibrillation by long-lasting AC shocks. In this study, long-lasting AC stimulus is applied to a computational model of cardiac architecture and fiber geometry based on the canine ventricles, in which a stable scroll wave has been induced. This study demonstrates that tissue entrainment by long-lasting high frequency shocks results in strong post-shock VEP, which result in higher defibrillation efficacy.; Results of this study elucidate the ability of long-lasting AC waveforms to entrain cardiac tissue, and illustrate the mechanisms by which depolarization is sustained during the shock. The study also reveals the frequency-dependent role of entrainment in successful cardioversion using long-lasting AC shocks. This study of long-lasting AC waveforms and their ability to defibrillate cardiac tissue contributes to the body of knowledge of defibrillation and explores mechanisms that could be further employed in the development of more efficient AC defibrillation protocols.