The effects of
saralasin on electrophysiological changes and arrhythmias induced by simulated
ischemia and reperfusion were examined in an isolated tissue model. Segments of guinea pig right ventricles, stimulated regularly, were exposed to simulated
ischemia for 15 min and then were reperfused with normal
Tyrode's solution for 30 min. Transmembrane electrical activity and a high-gain electrogram were recorded. Arrhythmias and electrophysiological changes accompanying simulated
ischemia and reperfusion in control preparations were compared to those in preparations treated with 0.1 or 1 microM
saralasin. Simulated
ischemia caused abbreviation of action potential duration measured at 90% repolarization, 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. Rapid sustained or
nonsustained ventricular tachycardia occurred in approximately 60% of control preparations in early reperfusion. The overall incidence of arrhythmias and the incidence of
ventricular tachycardia in early reperfusion were significantly decreased by 1 microM but not 0.1 microM
saralasin.
Saralasin (1 microM) prolonged the ERP in normoxic tissues, but it did not alter changes induced by
ischemia or reperfusion in ERP or the action potential duration at 90% repolarization. Prolongation of transmural conduction time during
ischemia and early reperfusion was significantly inhibited by both concentrations of
saralasin. However, only 1 microM
saralasin reduced the ratio of transmural conduction time to ERP enough to prevent arrhythmias. Our observations demonstrate that
saralasin exerts antiarrhythmic effects in myocardial reperfusion by a mechanism independent of circulatory and central actions.