Stereospecific antiarrhythmic effect of opioid receptor antagonists in myocardial ischaemia.

The effects of the stereoisomers of two different antagonists at opioid receptors were examined on the ventricular arrhythmias that result from acute coronary artery ligation in anaesthetized male rats. (-)-Mr 1452(but not the (+)-isomer, Mr 1453) reduced, in a dose-dependent manner, the number of ventricular ectopic beats and the incidence or duration of both ventricular tachycardia and fibrillation. (-)-WIN 44,441-3 (but not its (+)-isomer, WIN 44,441-2) had a similar protective effect in ischaemia. These results suggest that antagonism of the effects of endogenous opioid peptides at specific receptors results in reduced severity of arrhythmias in myocardial ischaemia.