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

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Abstract
1 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. 2 Intravenously administered (-)- and (+)-verapamil dose-dependently reduced ventricular arrhythmias. (-)-Verapamil was consistently 4 times more potent than (+)-verapamil. 3 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. 4 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. 5 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. 6 These results are compatible with the hypothesis that calcium antagonism in the ischaemic ventricular myocardium is antiarrhythmic during acute myocardial ischaemia.