Antiarrhythmic Effects of Coronary Vasodilators on Canine Ventricular Arrhythmia Models

Abstract

Antiarrhythmic effects of intravenous coronary vasodilators (verapamil, diltiazem, bepridil, trimetazidine and nicorandil) were evaluated using two canine ventricular arrhythmia models (halothane-adrenaline arrhythmia and digitalis arrhythmia), and the minimum effective plasma concentrations of the drugs were determined for each arrhythmia model. Verapamil (0.1 mg/kg), diltiazem (0.1 mg/kg), bepridil (1 mg/kg) and high dose trimetazidine (10 mg/kg) were effective on halothane-adrenaline arrhythmia; and the minimum effective plasma concentrations of the above drugs were less than 30±10 ng/ml, less than 18±5 ng/ml, 0.38±0.11 μg/ml and 7.0±1.5 μg/ml, respectively. Nicorandil (1 mg/kg) did not suppress halothane-adrenaline arrhythmia. Verapamil, diltiazem and bepridil must have suppressed the halothane-adrenaline arrhythmia by blocking the Ca channel. Verapamil (1 mg/kg), diltiazem (1 mg/kg), bepridil (5 mg/kg), trimetazidine (3 mg/kg) and nicorandil (3 mg/kg) were ineffective on digitalis arrhythmia, even though their maximum hypotensive doses were used.