EFFECTS OF ACUTE GLOBAL ISCHEMIA ON RE-ENTRANT ARRHYTHMOGENESIS: A SIMULATION STUDY

Abstract

Sudden cardiac death is mainly caused by arrhythmogenesis. For a functional abnormal heart, such as an ischemic heart, the probability of arrhythmia occurring is greatly increased. During myocardial ischemia, re-entry is prone to degenerate into ventricular fibrillation (VF). Therefore it has important meaning to investigate the intricate mechanisms underlying VF under an ischemic condition in order to better facilitate therapeutic interventions. In this paper, to analyze the functional influence of acute global ischemia on cardiac electrical activity and subsequently on re-entrant arrhythmogenesis, we take into account three main pathophysiological consequences of ischemia: hyperkalaemia, acidosis, and anoxia, and develop a 3D human ventricular ischemic model that combines a detailed biophysical description of the excitation kinetics of human ventricular cells with an integrated geometry of human ventricular tissue which incorporates fiber direction anisotropy and the stimulation activation sequence. The results show that under acute global ischemia, the tissue excitability and the slope of ventricular cellular action potential duration restitution (APDR) are greatly decreased. As a result, the complexity of VF activation patterns is reduced. For the three components of ischemia, hyperkalaemia is the dominant contributor to the stability of re-entry under acute global ischemia. Increasing [K+]o acts to prolong the cell refractory period, reduce the tissue excitability and slow the conduction velocity. Our results also show that VF can be eliminated by decreasing cellular excitability, primarily by elevating the concentration value of extracellular K+.