AJP - Heart and Circulatory Physiology, Vol 258, Issue 6 1815-H1822, Copyright © 1990 by American Physiological Society
Differential sensitivity of cardiac pacemakers to exogenous adenosine in vivo
A. Pelleg, C. Hurt, A. Miyagawa, E. L. Michelson and L. S. Dreifus
Lankenau Medical Research Center, Hahnemann University, Philadelphia, Pennsylvania 19102-1192.
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)
