Effects of dual endothelin receptor blockade on sympathetic activation and arrhythmogenesis during acute myocardial infarction in rats

Abstract The effects of dual (ETA and ETB) endothelin receptor blockade on ventricular arrhythmogenesis during acute myocardial infarction are not well defined. We randomly allocated Wistar rats to bosentan (100 mg/kg daily, n  = 24), a dual endothelin receptor antagonist, or vehicle ( n  = 23). After 7 days of treatment, myocardial infarction was induced by permanent coronary ligation. Ventricular tachyarrhythmias were evaluated for 24 h following ligation, using a miniature telemetry electrocardiogram recorder. Action potential duration was measured from monophasic epicardial recordings and sympathetic activation was assessed by heart rate variability and catecholamine serum level measurements. Compared to controls (1012 ± 185 s), bosentan (59 ± 24 s) markedly decreased ( P P  = 0.053). Treatment did not affect infarct size or total mortality. Action potential duration at 90% repolarization prolonged in controls (from 93.1 ± 4.7 ms to 117.6 ± 6.9 ms), displaying increased temporal dispersion (from 4.14 ± 0.45 ms to 10.42 ± 2.51 ms, both P