Antagonistic effects of alpha-adrenoceptor blocking agents on arrhythmias, enzyme release, and myocardial necrosis in isolated rat hearts with coronary occlusion and reperfusion

Abstract

In isolated perfused rat hearts reperfusion of the occluded left coronary artery led to arrhythmias, their severity depending on the duration of the foregoing period of myocardial ischaemia. Simultaneously, high activities of the myocardial enzyme creatine kinase (CK) were released into the perfusion fluid. Corynanthine, blocking mainly alpha 1-adrenoceptors, and rauwolscine, blocking mainly alpha 2-adrenoceptors, concentration-dependently antagonized the reperfusion-induced arrhythmias (3-30 mumol/l). The most severe kind of arrhythmia, i.e., ventricular fibrillation was completely prevented by 30 mumol/l of either drug. Also arrhythmias occurring already during the period of coronary occlusion were antagonized, as tested with corynanthine. The beta 1-adrenoceptor blocking agent metoprolol (1, and 10 mumol/l) had no effect at all against reperfusion arrhythmias, and the mainly alpha 1-adrenoceptor stimulating agent phenylephrine markedly increased the severity of these rhythm disturbances. The release of creatine kinase during the coronary reperfusion was significantly decreased by corynanthine, while the effect of rauwolscine was smaller and non-significant. Phenylephrine markedly increased the enzyme leakage from the myocardium. In all hearts the extent of the ischaemic and necrotic areas was determined. The percentage of the previously ischaemic area found necrotic at the end of the reperfusion, depended on the duration of the coronary occlusion. Corynanthine in a highly significant way decreased the area of myocardial necrosis, an effect obtained to some extent also with rauwolscine. The findings suggest that alpha-adrenoceptor stimulation is involved in the genesis of arrhythmias and myocardial damage associated with myocardial ischaemia and reperfusion. Possible mechanisms of action of corynanthine and rauwolscine are discussed, especially in view of the interrelationship between alpha-adrenoceptors and slow calcium channels.