Evidence for adenosine mediation of atrioventricular block in the ischemic canine myocardium.

Abstract

A B S T R A C T Adenosine levels in oxygen-deprived myocardium can rise to 10-100-,uM concentrations known to cause atrioventricular (AV) conduction delay and block. We reported that the AV conduction delay and block caused by hypoxia is markedly attenuated by 10 ,uM aminophylline, an adenosine competitive antagonist. The purpose of the present study was to investigate adenosine's role in ischemic AV conduction disturbances. Dogs were anesthetized and instrumented for His bundle and surface electrogram recordings. The total AV conduction time was subdivided into atrial-His bundle (AH) and His bundleventricle intervals. The atrioventricular node artery (AVNA) was cannulated for selective injection of drugs in the AV node region. Adenosine (10 to 100 ,ug), as a 2-ml bolus injection, rapidly produced a dose-dependent, transient increase in the AH interval; a 1,000-,ug dose caused second degree AV block. The duration of the increase in AH interval was also dose-dependent. Dipyridamole, an inhibitor of nucleoside transport, potentiated the negative dromotropic effects ofadenosine, whereas aminophylline attenuated them. In some dogs, after cannulation of the AVNA, first and second degree AV block occurred spontaneously or were induced by rapid atrial pacing. Injection of the aminophylline (5 mg/kg, i.v.) or theophylline (100-1,000 gg) into the AVNA rapidly reversed the AV blocks. Upon washout of the drugs the AV blocks recurred. We conclude that endogenously released adenosine may account for a major fraction of the AV conduction delay and block associated with impaired blood supply to the AV node, and that theophylline and aminophylline reverse the AV conduction defect by antagonizing the effects of adenosine. INTRODUCTION It has been demonstrated that adenosine and related compounds can produce heart block (1, 2). Recently we (3) reported that the atrioventricular (AV)' conduction delay and block caused by adenosine is due solely to a prolongation of the atria-to-His bundle (A-H) interval. Adenosine is also known to depress Ca2+-mediated action potentials in mammalian atria (4, 5) as well as inhibit the "slow" Ca2+-Na+-mediated action potential in the A-V node (6). This suggests that the A-V node conduction defect is restricted to the slow channel-dependent tissue of the A-V node.During hypoxia, the A-V node action potentials are depressed and, concomitantly, the A-H conduction time is markedly increased (7). Furthernore, ischemia and asphyxia also impair A-V node transmission (8)(9)(10) and enhance the atrial and ventricular cardiac cell production of adenosine (11,12). In addition, in isolated perfused guinea pig hearts, aminophylline, a competitive antagonist ofadenosine, significantly attenuates and reverses the A-V conduction delay and block caused by adenosine and/or hypoxia (3). These findings have led us to hypothesize a causal role for adenosine in the A-V conduction block seen during hypoxia. The objective of this study is to investigate the role of adenosine in the mediation of A-V conduction disturbances...

Relative Perioperative Bradycardia Does Not Lead to Adverse Outcomes After Cardiac Transplantation

“…The mechanism for this effect may be the release of adenosine in the allograft in response to injury or reperfusion (15). The transplanted, denervated heart has been shown to be supersensitive to the effects of adenosine (16) which can suppress sinus node automaticity and AV node conduction.…”

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

“…Dipyridamoie alone terminated SVT (and prevented reinduction) Adenosine production is increased in response to ischemia and hypoxia and functions to restore a physiologic 02 supply-demand ratio.7,8 For instance, increased adenosine release during myocardial hypoxia improves 02 supply by coronary vasodilation8 and decreases 02 demand by precipitating sinus bradycardia,9 AV block,10 and antagonizing the effects of sympathomimetic amines." [1][2][3][4][5][6][7][8][9][10][11][12][13] The electrophysiologic effects of adenosine have been primarily demonstrated by administering an exogenous preparation of the nucleoside because endogenous adenosine is not believed to be produced in sufficient amounts to have significant effects during normoxic conditions.1415 Recent evidence from studies in guinea pigs, however, suggests the contrary, that is, endogenous adenosine may have some physiologic role under normoxic conditions. 16 The purpose of this study was ProtocolA.…”

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

“…Dipyridamole (a drug that protects against adenosine degradation by blocking its uptake into cells and hence its deamination to inosine) potentiates and methylxanthines (competitive adenosine antagonists) attenuate the hypoxia and ischemia-induced AH prolongation and AV block. 8 myocardial infarction or spasm of the right coronary artery), which are sometimes not responsive to treatment with atropine, adenosine antagonists may prove to be useful.…”