A study of early afterdepolarizations in human ventricular tissue

摘要

Early afterdepolarizations (EADs) are additional small amplitude spikes during the repolarization phase of the action potential. The presence of EADs strongly correlates with the onset of dangerous cardiac arrhythmias. Most in silico studies target various mechanisms of EAD formation and are mainly performed in animal models of cardiac cells and at a single cell level. However, most EAD-related cardiac arrhythmias feature complex spatial organization. Here, we first present our recent studies on 2D spatial wave patterns in models of human ventricular tissue with EAD-shaped action potentials. Next, we report on our first steps in studies of EAD-related arrhythmias in an anatomically accurate model of the human heart. For these studies, we use a TP06 model modified to mimic the effect of certain drugs. We show that from the initial conditions representing normal excitation of the heart, we can obtain two types of complex spatial patterns of excitation: (1) of the re-entrant type produced by Ca waves and mainly manifested as a complex focal activity on the surface of the heart, due to transmural filament orientation. For a more reduced repolarizaiton reserve, we also obtain (2) complex spatial oscillatory patterns of excitation.