Electrophysiologic effects of dipyridamole on atrioventricular nodal conduction and supraventricular tachycardia. Role of endogenous adenosine

Abstract

Exogenous adenosine has been shown to have potent electrophysiologic effects and antiarrhythmic properties within the atrioventricular (AV) node. Endogenous adenosine, a nucleoside with an increased release signaled by ischemia and hypoxia, is not believed to exert significant effects during homeostatic conditions. Recent experimental evidence suggests, however, that under normoxic conditions, the amount of adenosine released may be sufficient to mediate some of its physiologic effects. This study was designed to test the hypothesis that in humans the electrophysiologic effects of endogenously released adenosine on AV nodal conduction can be demonstrated under normoxic conditions by inhibiting uptake and degration of the nucleoside. In the first protocol, the effects of intravenous dipyridamole (0.56 gm/kg bolus i.v., 5 χ/kg/minute infusion), a nucleoside-transport blocker that elevates endogenous plasma levels of adenosine on AV nodal conduction were evaluated in seven patients. At a constant atrial paced cycle length, dipyridamole increased the AH interval from 110 ± 19 to 164 ± 26 msec, p = 0.002 (±SEM). Aminophylline (5.6 mg/kg i.v.), a competitive antagonist of adenosine, completely reversed the effects of dipyridamole on AV nodal conduction. Similarly, dipyridamole increased the cycle length at which pacing-induced AV nodal Wenckebach occurred, from 348 ± 31 (control) to 388 ± 33 msec (dipyridamole) (p = 0.002). In a second protocol, the effects of intravenous dipyridamole were evaluated in another group of six patients who had supraventricular tachycardia (SVT) in which the AV node was part of the reentrant circuit. Dipyridamole increased the cycle length of SVT from 344 ± 29 to 379 ± 30 msec (p < 0.05), effects that were confined primarily to the AV node (AH interval). Dipyridamole alone terminated SVT (and prevented reinduction) in one of six patients. In the remaining five patients, dipyridamole reduced fourfold the minimum-effective dose of exogenous adenosine required to terminate SVT, that is, from 68 ± 15 to 17 ± 6 μg/kg (p = 0.005). The results show that the electrophysiologic and antiarrhythmic properties of endogenous adenosine on the AV node may be demonstrated in the absence of ischemia by attenuating nucleoside transport and degradation. Although the effects of dipyridamole during SVT were modest, the results of this study suggest that the development of more potent and specific nucleoside-transport blockers that elevate endogenous adenosine levels may provide an effective therapeutic modality in patients with SVT.