Antiarrhythmic Effects of Coronary Vasodilators on Canine Ventricular Arrhythmia Models

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Abstract
Antiarrhythmic effects of i.v. coronary vasodilators (verapamil, diltiazem, bepridil, trimetazidine and nicorandil) were evaluated using 2 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 .mu.g/ml and 7.0 .+-. 1.5 .mu.g/ml, respectively. Nicorandil (1 mg/kg) did not suppress the 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.