Antiadrenergic effects of adenosine on His-Purkinje automaticity. Evidence for accentuated antagonism.
The effects of adenosine on the human His-Purkinje system (HPS) were studied in nine patients with complete atrioventricular (AV) block. Adenosine had minimal effect on the control HPS cycle length, but in the presence of isoproterenol increased it from 906 +/- 183 to 1,449 +/- 350 ms, P less than 0.001. Aminophylline, a competitive adenosine antagonist, completely abolished this antiadrenergic effect of adenosine. In isolated guinea pig hearts with surgically induced AV block, isoproterenol decreased the HPS rate by 36%, whereas in the presence of 1,3-dipropyl-8-phenyl-xanthine, a potent adenosine antagonist, the HPS rate decreased by 48% and was associated with an increased release of adenosine. Therefore, by blocking the effects of adenosine at the receptor level, the physiologic negative feedback mechanism by which adenosine antagonizes the effects of catecholamines was uncoupled. The results of this study indicate that adenosine's effects on the human HPS are primarily antiadrenergic and are thus consistent with the concept of accentuated antagonism. These effects of adenosine may serve as a counterregulatory metabolic response that improves the O2 supply-demand ratio perturbed by enhanced sympathetic tone. Some catecholamine-mediated ventricular arrhythmias that occur during ischemia or enhanced adrenergic stress may be due to an imbalance in this negative feedback system.
Lerman
B B
BB
Department of Medicine, University of Virginia Medical Center, Charlottesville 22908.
Wesley
R C
RC
DiMarco
J P
JP
Haines
D E
DE
Belardinelli
L
L
D000241:Adenosine / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002036:Bundle of His / Q000187:drug effects*; D004176:Dipyridamole / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006327:Heart Block; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010101:Oxygen Consumption; D011690:Purkinje Fibers / Q000187:drug effects*
D000628:Aminophylline; D004176:Dipyridamole; D001285:Atropine; D000241:Adenosine; D007545:Isoproterenol