Endothelin receptor - A blockade decreases ventricular arrhythmias after myocardial infarction in rats

Objective: Endothelin-1 (ET-1) production increases during acute myocardial infarction (MI) and may contribute to the genesis of ventricular tachycardia, (VT) and ventricular fibrillation (VF). However, the antiarrhythmic effects of ET-I receptor blockade, examined shortly after MI, have been debated. In the present study, we examined the effects of such treatment on VT/VF during the first 24 h post-MI. Methods: Thirty-five Wistar rats (223 +/- 22 g) were randomly allocated to either the ET-I receptor-A (ETA) antagonist BQ-123 (0.4 mg/kg, BQ-123 group, n=17), or normal saline (control group, n=18) and were subjected to coronary artery ligation. A single-lead electrocardiogram was continuously recorded for 24 h post-MI, using an implanted telemetry system, and episodes of VT/VF were analyzed. Monophasic action potential (MAP) recordings were obtained from the left (LV) and right (RV) ventricular epicardium at baseline, 5 min after treatment and 24 h post-MI. Results: There were 15.94 +/- 19.35 episodes/h/rat of VT/VF in the control group and 1.66 +/- 2.22 in the BQ-123 group (p=0.010), resulting in a lower (p=0.030) arrhythmic mortality in treated animals. The mean episode duration was 7.40 +/- 7.16 s for the control group and 2.30 +/- 1.37 s for the BQ-123 group (p=0.011). The maximum decrease in VT/VF was observed during the 1st, 5th and 6th hours post-MI. In the control group, LV MAP duration increased 24 It post-MI, displaying an increased beat-to-beat variation, but remained unchanged in the BQ-123 group. Conclusion: Acute ETA blockade reduces the incidence of VT/VF during the first 24-h post-MI in the rat, through a decrease in the dispersion of repolarization. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.