SARALASIN SUPPRESSES ARRHYTHMIAS IN AN ISOLATED GUINEA-PIG VENTRICULAR FREE-WALL MODEL OF SIMULATED ISCHEMIA AND REPERFUSION

The effects of saralasin on electrophysiological changes and arrhythmi as induced by simulated ischemia and reperfusion were examined in an i solated tissue model. Segments of guinea pig right ventricles, stimula ted regularly, were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode's solution for 30 min. Transmembran e electrical activity and a high-gain electrogram were recorded. Arrhy thmias and electrophysiological changes accompanying simulated ischemi a and reperfusion in control preparations were compared to those in pr eparations treated with 0.1 or 1 mu M saralasin. Simulated ischemia ca used abbreviation of action potential duration measured at 90% repolar ization, abbreviation of endocardial effective refractory period (ERP) and prolongation of transmural conduction time. Premature ventricular beats, ventricular tachycardia and conduction block were observed in approximately 35% of control preparations during simulated ischemia. R apid sustained or nonsustained ventricular tachycardia occurred in app roximately 60% of control preparations in early reperfusion. The overa ll incidence of arrhythmias and the incidence of ventricular tachycard ia in early reperfusion were significantly decreased by 1 mu M but not 0.1 mu M saralasin. Saralasin (1 mu M) prolonged the ERP in normoxic tissues, but it did not alter changes induced by ischemia or reperfusi on in ERP or the action potential duration at 90% repolarization. Prol ongation of transmural conduction time during ischemia and early reper fusion was significantly inhibited by both concentrations of saralasin . However, only 1 mu M saralasin reduced the ratio of transmural condu ction time to ERP enough to prevent arrhythmias. Our observations demo nstrate that saralasin exerts antiarrhythmic effects in myocardial rep erfusion by a mechanism independent of circulatory and central actions .