Campos Fernando O, Shiferaw Yohannes, Vigmond Edward J, Plank Gernot
Department of Congenital Heart Diseases and Pediatric Cardiology, German Heart Institute Berlin, Berlin, Germany.
Department of Physics, California State University, Northridge, California 91330, USA.
Chaos. 2017 Sep;27(9):093910. doi: 10.1063/1.4999612.
Premature ventricular complexes (PVCs), the first initiating beats of a variety of cardiac arrhythmias, have been associated with spontaneous calcium release (SCR) events at the cell level. However, the mechanisms underlying the degeneration of such PVCs into arrhythmias are not fully understood. The objective of this study was to investigate the conditions under which SCR-mediated PVCs can lead to ventricular arrhythmias. In particular, we sought to determine whether sodium (Na) current loss-of-function in the structurally normal ventricles provides a substrate for unidirectional conduction block and reentry initiated by SCR-mediated PVCs. To achieve this goal, a stochastic model of SCR was incorporated into an anatomically accurate compute model of the rabbit ventricles with the His-Purkinje system (HPS). Simulations with reduced Na current due to a negative-shift in the steady-state channel inactivation showed that SCR-mediated delayed afterdepolarizations led to PVC formation in the HPS, where the electrotonic load was lower, conduction block, and reentry in the 3D myocardium. Moreover, arrhythmia initiation was only possible when intrinsic electrophysiological heterogeneity in action potential within the ventricles was present. In conclusion, while benign in healthy individuals SCR-mediated PVCs can lead to life-threatening ventricular arrhythmias when combined with Na channelopathies.
室性早搏(PVCs)是多种心律失常的首个起始搏动,在细胞水平上与自发钙释放(SCR)事件相关。然而,此类PVCs演变为心律失常的潜在机制尚未完全明确。本研究的目的是探究SCR介导的PVCs导致室性心律失常的条件。具体而言,我们试图确定结构正常的心室中钠(Na)电流功能丧失是否为SCR介导的PVCs引发的单向传导阻滞和折返提供了基础。为实现这一目标,将SCR的随机模型纳入包含希氏-浦肯野系统(HPS)的兔心室解剖学精确计算模型中。由于稳态通道失活的负向移位导致钠电流降低的模拟结果显示,SCR介导的延迟后去极化在HPS中导致PVC形成,HPS处的电紧张负荷较低,三维心肌中出现传导阻滞和折返。此外,只有当心室内动作电位存在固有电生理异质性时,心律失常才会起始。总之,虽然SCR介导的PVCs在健康个体中是良性的,但与钠通道病合并时可导致危及生命的室性心律失常。