Differences in the electrophysiological response of canine ventricular epicardium and endocardium to ischemia. Role of the transient outward current.

BACKGROUNDAcute 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 (Ito) 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 Ito in epicardium than in endocardium.METHODS AND RESULTSIsolated canine ventricular epicardial and endocardial tissues and myocytes were studied by standard microelectrode techniques. Simulated ischemia (hyperkalemia, hypoxia, and acidosis) abolished the action potential plateau and caused a 50% to 60% shortening of action potential duration in epicardium but only a 10% to 20% shortening in endocardium. 4-Aminopyridine, an Ito inhibitor, restored the plateau in epicardium and reduced t...