Mechanisms of action and therapeutic potential of adenosine and its analogues in the treatment of cardiac arrhythmias

Abstract

Adenosine is a purine nucleoside found in every cell of the human body. In addition to its well-established role in cellular metabolism, extracellular adenosine exerts pronounced effects on the cardiovascular system. These effects, mediated by specific cell surface receptors, include a negative chronotropic effect on cardiac pacemakers, a negative dromotropic effect on atrioventricular nodal conduction, an antiadrenergic effect, and a vasodilatory effect on blood vessels. In addition, adenosine can attenuate platelet aggregation and neutrophil activation and alter cardiac metabolism. Its electrophysiologic effects on atrioventricular nodal conduction constitute the rationale for the use of adenosine as an antiarrhythmic drug for the acute management of paroxysmal reentrant supraventricular tachycardias involving the atrioventricular node, as well as for its use as a diagnostic tool in broad complex tachycardias and in preexcitation. The antiadrenergic action of adenosine explains its potential use in the acute management of catecholamine-dependent ventricular tachycardias. Several of the other effects of adenosine suggest the use of this compound as well as its analogues as cardioprotective agents in the setting of myocardial ischemia (occlusion then reperfusion of coronary vessels, cardioplegia, coronary angioplasty, thrombolysis, and so forth).