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Losartan but not enalaprilat acutely reduces reperfusion ventricular tachyarrhythmias in hypertrophied rat hearts after low‐flow ischaemia

Based on clinical and experimental studies, angiotensin II receptor blockers and angiotensin converting enzyme inhibitors have been proposed to exert acute anti‐arrhythmic effects in heart failure patients. Therefore, the goal of this study was to assess acute anti‐arrhythmic effects of losartan and enalaprilat in hypertrophied rat hearts during low‐flow ischaemia and reperfusion. In dose‐finding experiments in non‐hypertrophied isolated perfused hearts, we performed dose‐response curves of losartan and enalaprilat studying monophasic action potential duration at 90% repolarisation (MAPD90%) and ventricular fibrillation (VF) threshold. Subsequently, we determined the effects of losartan and enalaprilat (in therapeutically relevant concentrations) on ventricular tachyarrhythmias induced by low‐flow ischaemia/reperfusion in hearts demonstrating left ventricular (LV) hypertrophy 70 days after aortic banding. We found that neither drug significantly affected MAPD90% (1 nm‐1 mm) or VF threshold (1 μm losartan and 10 μm enalaprilat) in non‐hypertrophied hearts. Similarly in hypertrophied hearts, neither drug significantly affected the incidence or the duration of ventricular tachyarrhythmias (ventricular tachycardia and VF) during low‐flow ischaemia. However, 1 μm losartan significantly reduced the duration of ventricular tachyarrhythmias during reperfusion. In conclusion, neither losartan nor enalaprilat is acutely anti‐arrhythmic in hypertrophied rat hearts during low‐flow ischaemia. During reperfusion, however, losartan but not enalaprilat exerts acute anti‐arrhythmic effects.