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

Abstract

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 automaFrom the Departments of Physiology/Medicine and Division of Cardiology, University of Virginia, Charlottesville.The studies cited in this review were supported in part by grant-in-aid 81-911 from the American Heart Association, AHA-Virginia Affiliate, and from NHLBI (HL10384 and HL-3111). ticity, spontaneous depolarization is inhibited. These effects of adenosine have been attributed to an increase in K' conductance."'-'' Catecholamine-induced triggered automaticity is also prevented by the addition of adenosine to the media.'4 Direct effects of adenosine on isolated ventricular myocytes are less marked, but the effects of isoproterenol on the action potential duration of these cells is antagonized by adenosine. 14 In all of these systems, the effects of adenosine are potentiated by inhibitors of adenosine uptake (e.g., dipyridamole) and antagonized by methylxanthines. Less permeable analogues of adenosine retain electrophysiologic activity, suggesting that the effects of adenosine are mediated by a receptor located on the extracellular surface of the plasma membrane.6 Although significant interspecies differences in sensitivity to adenosine have been noted, qualitatively similar effects have been reported in all mammalian species studied, including man.Of interest was the finding that when AV nodal conduction was impaired by interventions, such as hypoxia or ischemia, that caused increas...

Effects of Exogenous Adenosine in a Patient with Transplanted Heart. Evidence for Adenosine as a Messenger in Angina Pectoris

“…The patient experienced respiratory stimulation at dl dosages also in accordance with previous findings (1,12).…”

“…The response did not differ from the reference values (table 1). The flow responses shown in table 1 are after intracoronary and intravenous injection of 1 mg respectively 5 mg adenosine. These doses were choosen because they were given to all of the tested subjects.…”

Circulatory and respiratory effects of infused adenosine in conscious man.

“…Adenosine has been reported to induce a fall in peripheral vascular resistance and systemic blood pressure (Hedqvist & Fredholm, 1979), and to reduce heart rate and depress atrioventricular conduction (Drury & Szent-Gyorgi, 1929;Berne et al, 1984). More recently adenosine infusions in conscious man have been reported to increase heart rate and widen pulse pressure (Biaggioni et al, 1986) in a dose dependent fashion.…”

Effect of infused adenosine on cardiac output and systemic resistance in normal subjects.

“…It is also a coronary vasodilator (Watt et al, 1987). It has been used clinically to prevent platelet aggregation , as an anti-arrythmic agent (Berne et al, 1984;Clarke et al, 1987) and as a systemic vasodilator during anaesthesia Torsell et al, 1985). Its short half-life potentially makes its effects easy to control.…”