Negative dromotropism of adenosine under beta-adrenergic stimulation with isoproterenol

Abstract

Adenosine depresses atrioventricular (AV) nodal function by binding to specific A 1 receptors which activate the acetylcholine, adenosine-regulated potassium current. In addition, adenosine can act to antagonize the effects of β-adrenergic stimulation on AV nodal function. To assess the negative dromotropic effects of adenosine under β-adrenergic stimulation, 15 patients were studied during clinical electrophysiologic study. During high right atrial pacing at a cycle length of 400 to 600 ms, adenosine was injected intravenously at an initial dose of 0.5 mg followed by a stepwise increment of 0.5 or 1.0 mg given at 5-minute intervals until a maximal dose of 12 mg was achieved or AV block developed. Intravenous isoproterenol (1 to 3 μg/min) was then infused to accelerate sinus rate by 20 to 30% during which intravenous injection of incremental doses of adenosine as described was repeated. The AV nodal conduction time (AH interval) was measured at each dose of adenosine. Dose-response curves of AV nodal conduction time (expressed as percent increase in AH interval) were studied during the control state and during isoproterenol infusion. The dose of adenosine required to produce AV nodal Wenckebach block, the increase in the AH interval by 50% (ED 50) and the maximal response (E max) were 3.4 ± 0.9 mg, 1.8 ± 0.9 mg and 60 ± 4%, respectively, in the control state, and 3.7 ± 0.8 mg, 2.0 ± 0.7 mg and 56 ± 4%, respectively, during isoproterenol infusion. No significant changes in ED 50, E max and the dose of adenosine yielding AV nodal Wenckebach block could be demonstrated between the control state and during isoproterenol infusion. Thus, the negative dromotropic effects of adenosine on AV nodal conduction remained unchanged with β-adrenergic stimulation. These findings suggest that adenosine may remain efficacious in terminating catecholamine-sensitive supraventricular tachycardia involving the AV node as part of the reentrant circuit.