Mechanisms involved in reperfusion arrhythmias.

Clinical and experimental studies indicate that reperfusion of the ischaemic myocardium may play an important role in the genesis of life-threatening arrhythmias. Reflow may occur as a result of abrupt cessation of coronary artery spasm or upon dislodgment of platelet aggregates with the attendant washout of products of cellular ischaemia. The released substances exert a transient but potent arrhythmogenic effect. Calcium channel blocking agents, by virtue of their broad spectrum of action, can interrupt the cascade of events leading to arrhythmias. In experimental animals, verapamil has been shown to reduce vulnerability to ventricular fibrillation during sympathetic stimulation and to prevent spontaneous fibrillation during both myocardial ischaemia and reperfusion. Comparable antifibrillatory effects have been observed with diltiazem and prenylamine. Tiapamil is effective during sympathetic stimulation and myocardial ischaemia but not during reperfusion. Nifedipine appears to exert a moderate antifibrillatory influence during myocardial ischaemia and is ineffectual in preventing reperfusion-induced fibrillation. These observations indicate that calcium channel blocking agents differ considerably in their ability to suppress arrhythmias during myocardial ischaemia and reperfusion. Their effectiveness appears to depend critically both on the pathophysiologic mechanisms and on the pharmacologic profile of the individual agent.