LOSARTAN EXERTS ANTIARRHYTHMIC ACTIVITY INDEPENDENT OF ANGIOTENSIN-IIRECEPTOR BLOCKADE IN SIMULATED VENTRICULAR ISCHEMIA AND REPERFUSION

The purpose of this study was to determine whether specific angiotensi n II (All) type 1 receptor blockade with losartan would affect arrhyth mia generation in an isolated guinea pig ventricular model of simulate d ischemia and reperfusion, Effects of losartan were evaluated in the presence and absence of exogenous All. Transmembrane potentials and an electrocardiogram were recorded during-perfusion with normal Tyrode's solution, exposure to simulated ischemia for 15 min (hypoxia, acidosi s, lactate, hyperkalemia, glucose-free) and reperfusion for 30 min, Un der normal conditions, losartan did not affect endocardial or transmur al conduction times, action potential duration at 90% repolarization o r effective refractory period (ERP). However, losartan and All each ha d significant effects on electrophysiological parameters during simula ted ischemia and reperfusion. Further, losartan and All, both independ ently and in combination, exerted antiarrhythmic effects in early repe rfusion. Neither losartan nor All affected action potential duration a t 90% repolarization during simulated ischemia or reperfusion. However , All exerted antiarrhythmic effects by preventing pronounced shorteni ng of ERP in simulated ischemia and early reperfusion. Losartan by its elf had no effect on ERP. Nevertheless, losartan preserved antiarrhyth mic efficacy by attenuating prolongation of transmural conduction time s in simulated ischemia and early reperfusion. This antiarrhythmic act ion occurred in the absence or presence of All. Our results indicate t hat losartan has antiarrhythmic efficacy which is independent of All t ype 1 receptor blockade.