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 degradation of the nucleoside. In the first protocol, the effects of intravenous dipyridamole (0.56 mg/kg bolus i.v., 5 ,ug/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). Dipyridamoie alone terminated SVT (and prevented reinduction) in one of six patients. In the remaining five patients, dipyridamole reduced fourfold the minimum-efective dose of exogenous adenosine required to terminate SVT, that is, from 68±15 to 17+6 ,ug/kg (p=0.005). These 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 elfects 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 elfective therapeutic modality in patients with SVT. (Circulation 1989;80:1536-1543 A denosine is a unique endogenous nucleoside adenosine A1 receptor to K' channels by a guaninewith potent, site-specific electrophysiologic nucleotide-regulatory binding protein, Gk3'4 (although effects and antiarrhythmic properties within an effect on calcium channels has not been entirely the atrioventricular (AV) node.1'2 Similar to its action ruled out). Activation of K' channels by adenosine, in atrial myocytes, adenosine is believed to mediate which hyperpola...

Cardiac purinergic signalling in health and disease

“…The mechanism of terminating the arrhythmias by either adenosine or ATP is the induction of transient complete AV nodal conduction block. Dipyridamole, which inhibits the uptake of adenosine and thereby increasing its extracellular levels, was found to reduce the amount of adenosine required for the termination of PSVT involving the AV node [667]. In contrast, it has been suggested that caffeine (a non-selective adenosine receptor antagonist) ingestion reduces adenosine efficacy in the treatment of PSVT [668], although, the methodology of the latter study was subsequently criticised [669].…”

Cardiac electrophysiology of adenosine. Basic and clinical concepts.

“…Consistent with experimental findings, adenosine shortens action potential duration and refractoriness.62 These effects may precipitate atrial flutter or fibrillation and is the mechanism by which nucleoside transport blockers like dipyridamole induce atrial flutter that is reversed by aminophylline. 63 AV node. Adenosine slows conduction within the AV node (negative dromotropy), which can result in transient AV block.54,64 Intracardiac recordings demonstrate that heart block is preceded by prolongation of the A-H interval, effects that are unaltered by atropine.…”

“…The adenosine dose should be reduced to one fourth of the usual dose since dipyridamole potentiates the effects and half-life of adenosine. 63 Patients who are taking competitive antagonists such as theophylline or caffeine may require larger than usual doses of adenosine, although doses as high as 19 mg have been ineffective in patients on theophylline. 70 In heart transplant patients who develop PSVT, the adenosine dose should be reduced to one third to one fifth of the usual dose due to denervation-induced supersensitivity to the drug.…”

Atrial fibrillation after intravenous dipyridamole for thallium imaging

“…In addition, adenosine also prolongs intra-atrial conduction times (Bubinski et al 1989). These effects are thought to be important in the occasional cases of induction by adenosine of atrial flutter (DiMarco et al 1985;Lerman et al 1989). It is likely, therefore, that the induction of atrial fibrillation in this patient by dipyridamole was by a similar mechanism, particularly as no reversible myocardial ischaemia could be demonstrated by thallium tomography.…”