Dromotropic effects of adenosine and adenosine antagonists in the treatment of cardiac arrhythmias involving the atrioventricular node.

THE ELECTROPHYSIOLOGIC EFFECTS of adenosine and other adenine derivatives were first described by Drury and Szent-Gyorgyi in 1929.' These investigators clearly demonstrated that intravenous administration of adenosine produced a decrease in sinus rate and transient atrioventricular (AV) block. Adenosine is a mediator of many physiologic phenomena and most of the interest in its effects on the cardiovascular system have, until recently, been centered on its ability to regulate regional blood flow in the heart and other organs. During the last several years, we and several other investigators have reexamined the electrophysiologic effects of adenosine.2'6 In our initial experiments, we showed that adenosine produced variable degrees of dose-related reversible AV block in guinea pig and rabbit hearts perfused by the Langendorff technique. The negative dromotropic effect was localized to AV nodal tissue.5 6 In the anesthetized dog, perfusion of the sinus and AV nodal arteries with solutions containing adenosine produced a decrease in sinus nodal discharge and an increase in AV nodal conduction time, respectively.3'4' 7,8 Studies in isolated segments of the AV node and the isolated perfused mammalian heart have confirmed the earlier observations that adenosine impairs conduction through AV nodal tissue, and that its action is restricted to the proximal portion of the node, i.e., the slow channel-dependent tissue of the AV node.9 In addition to these effects on the sinoatrial and AV nodes, adenosine shortens the action potential duration and hyperpolarizes the membrane of atrial cells. '° " In isolated atrial cells with intrinsic automa-