A POSSIBLE INVOLVEMENT OF SODIUM-CHANNEL BLOCKADE OF CLASS-I-TYPE ANTIARRHYTHMIC AGENTS IN POSTISCHEMIC CONTRACTILE RECOVERY OF ISOLATED, PERFUSED HEARTS

The present study was undertaken to test the hypothesis that the degre e of sodium channel blockade by class-I-type antiarrhythmic agents acc ounts for enhancement of postischemic contractile recovery of ischemic /reperfused hearts. Electrophysiological studies showed that the class -I-type antiarrhythmic agents quinidine, disopyramide, procainamide, l idocaine mexiletine, flecainide and pilsicainide suppressed the V-max value of the rat left ventricular muscle cell, a marker of sodium chan nel blockade, in a concentration-dependent manner. Isolated rat hearts were subjected to 35 min of ischemia and 60 min of reperfusion. Posti schemic contractile recovery, which was never detected in untreated he arts, was enhanced in hearts pretreated with these antiarrhythmic agen ts during the last 3 min before ischemia at concentrations ranging fro m 3 to 300 mu M. Tissue Na, but not Ca, accumulation was also detected in the ischemic heart, and tissue Na and Ca accumulation was observed in the reperfused heart, which suggests that sodium overload occurs d uring ischemia, followed by sodium and calcium overload during reperfu sion. The degree of postischemic contractile recovery seen in the pres ence of these antiarrhythmic agents was inversely related to tissue Na or Ca accumulation after reperfusion, which suggests that class-I-typ e antiarrhythmic agents inhibit sodium overload occurring in ischemic/ reperfused myocardial cells. A close relationship between postischemic contractile recovery of the perfused heart and depression in the V-ma x value of the ventricular muscle was also observed. These results sug gest that the ability of class-I-type antiarrhythmic agents to inhibit myocardial sodium channels plays a significant role in the enhancemen t of postischemic contractile recovery of the ischemic/reperfused hear t.-