[Show abstract][Hide abstract] ABSTRACT: Ventricular arrhythmias are commonly observed in patients with ischemia. It is reported that the electrophysiological changes evoked by ischemia are greater in the epicardium than in the endocardium. To investigate the effects of this heterogeneity on transmural reentry, the computer simulation method is used. A two-dimensional model which can reproduce the endocardial, epicardial and middle cell types, approximate the ischemic characteristics and distribution of the ischemic severity is developed by setting different ratios of the maximum conductance of the rapid and slow inward rectifier potassium currents and considering the three major component conditions of acute ischemia at the ionic level. The results demonstrate that action potentials of the ischemic cells have elevated resting potential, shortened duration, slowed upstroke and declined amplitude. Conduction velocity is much more depressed in the epicardium because of the ischemia-induced transmural gradient of excitability. The epicardially initiated activation has wider vulnerable window and more possibility to cause unidirectional propagation even reentry. Dispersion of the excitability is proposed to be the underlying mechanism.
General Physiology and Biophysics 03/2010; 29(1):12-22. DOI:10.4149/gpb_2010_01_12 · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ventricular arrhythmias are commonly observed in patients with acute coronary occlusion and ischemia. The purpose of the present study is to determine ischemic electrophysiological effects and their role in ischemia-induced arrhythmia. Optical mapping of the membrane potential with voltage-sensitive dyes was used in the study. The mapping was performed with di-4-ANEPPS in Langendorff-perfused rabbit hearts. The excitation-contraction decoupler 2,3-butanedione monoxime was used to suppress motion artifacts caused by contraction of the heart. The acute global ischemia was developed by a rapid reduction of the flow rate. The experiments revealed that ischemic tissues were characterized by an obvious reduction in action potential duration and action potential upstroke, slower conduction velocity (CV) and the property of post-repolarization refractoriness. Moreover, the magnitude of CV reduced both in control and ischemia when the pacing cycle length was short. CV reduction was even early in ischemia, resulting in a broader curve during ischemia. Moreover, the dominant frequency of ventricular tachycardia/ventricular fibrillation (VT/VF) in ischemia was less than that in control, implying a decreasing tendency of VT/VF frequency for low excitability. Therefore, combined with our previous simulation study, the dynamic changes of CV and longer refractory period were suggested to play an important role in the ischemia-related arrhythmia. Low excitability in ischemic tissue was the fundamental mechanism in it.