Role of the Transient Outward Current

Background. Acute ischemia is known to produce more severe electrophysiological disturbances in canine ventricular epicardium than endocardium, although the mechanism for the differential sensitivity is still unresolved. Recent studies have demonstrated the presence of a prominent transient outward current (It.) in ventricular epicardium but not endocardium. The present study was designed to test the hypothesis that the differential sensitivity of these two tissues to ischemia results, at least in part, from a more prominent I,. in epicardium than in endocardium. Methods and Results. Isolated canine ventricular epicardial and endocardial tissues and myocytes were studied by standard microelectrode techniques. Simulated ischemia (hyperkalemia, hypoxia, and acido-sis) abolished the action potential plateau and caused a 50 % to 60 % shortening of action potential duration in epicardium but only a 10 % to 20%o shortening in endocardium. 4-Aminopyridine, an I,0 inhibitor, restored the plateau in epicardium and reduced the dispersion of action potential duration between epicardium and endocardium. Stimulation protocols that minimized the contribution of I,, such as acceleration of the stimulation rate or introduction of early premature beats, produced a paradoxical prolongation of the epicardial response caused by restoration of the action potential dome. Thus, ischemia-induced dispersion of repolarization was greatly diminished at rapid rates and after prematur