The mechanism of action of the optical enantiomers of verapamil against ischaemia-induced arrhythmias in the conscious rat.

Abstract

The actions of (-)-verapamil (0.2-6 mg kg-1) and (+)-verapamil (0.4-12 mg kg-1) against arrhythmias induced by coronary artery occlusion were studied in conscious rats. Intravenously administered (-)- and (+)-verapamil dose-dependently reduced ventricular arrhythmias. (-)-Verapamil was consistently 4 times more potent than (+)-verapamil. In the same animals, (-)-verapamil was approximately 4 times more potent than (+)-verapamil for effects on heart rate and blood pressure. Both enantiomers prolonged P-R interval, but had no effect on QRS interval. In separate groups of conscious rats, neither enantiomer influenced the threshold voltage and pulse width required to elicit fibrillo-flutter, or altered the maximum following frequency, during electrical stimulation of the left ventricle. In isolated, paced, Langendorff-perfused ventricles of the rat, both enantiomers dose-dependently reduced contractility, (-)-verapamil being 8-21 times more potent than (+)-verapamil; both absolute and relative potencies were dependent on potassium concentration. These results are compatible with the hypothesis that calcium antagonism in the ischaemic ventricular myocardium is antiarrhythmic during acute myocardial ischaemia.