Differential sensitivity of cardiac pacemakers to exogenous adenosine in vivo

Adenosine exerts pronounced depressant effects on cardiac pacemakers. Previous studies in vitro have indicated that different pacemakers exhibit variable sensitivity to adenosine: ventricular greater than junctional greater than sinus node pacemakers. This study tested the hypothesis that ventricular pacemakers are more sensitive to adenosine than sinus node pacemakers in vivo in an experimental canine model and determined the mechanism involved in this phenomenon using specific pharmacological interventions. For this purpose, dogs with chronic atrioventricular block, stable ventricular escape rhythm, and bilateral stellectomy and cervical vagotomy were studied. Dose-response curves for negative chronotropic action of adenosine in the sinus node and ventricular pacemakers were obtained in group 1 under base-line conditions, during isoproterenol infusion, and after subsequent administration of propranolol; in group 2 before and after administration of quinidine; in group 3 before and after administration of aminophylline; and in group 4 before and after administration of 1,3-dipropyl-8-phenylxanthine amine congener (XAC). Adenosine exerted a dose-dependent negative chronotropic effect on sinus node and ventricular pacemakers. At all doses tested, this action was more pronounced in the ventricle. Isoproterenol accentuated the action of adenosine in the sinus node (by 60-138%; P less than 0.05) but suppressed it in the ventricle (-37 to 53%; P less than 0.05). These effects of isoproterenol were attenuated by propranolol. Quinidine suppressed the action of adenosine in the sinus node (-38 to -52%; P less than 0.05) but not in the ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)