Age-associated decrease in heart rate response to isoproterenol in dogs

Aging results in a decrease in the maximum heart rate during exercise. To determine if the age-associated decline in maximal heart rate might be due to a decreased chronotropic response to catecholamines, the maximum heart rate induced by systemic injections of isoproterenol was compared in unanesthetized mature (1-4 year) and senescent (8-12 year) beagle dogs. Maximum rate was also assessed under pentobarbital anesthesia before and after cholinergic blockade with atropine. The unanesthetized baseline heart rates in the mature and senescent groups did not differ [148 ± 6 vs. 147 ± 7 beats/min (bpm)] but the maximum isoproterenol induced heart rate was lower in the senescent compared to the mature group (249 ± 7 vs. 286 ± 13 bpm, P < 0.03). After pentobarbital anesthesia the baseline heart rates also did not differ and the age difference in maximum heart rate persisted (senescent: 220 ± 8 bpm; mature: 260 ± 10 bpm; P < 0.02). The maximum heart rates were not affected by atropine. In contrast to the age difference in maximum rate after isoproterenol, both mature and senescent dogs could be paced electrically to a rate greater than two times the maximum drug induced heart rate. Dose-response curves under anesthesia demonstrated a diminished response in the aged group. These studies demonstrate an age-associated decline in chronotropic response and suggest that the mechanism responsible is located in the beta-adrenergic system and is not due to an age decrement in response of the pacemaker cells to direct electrical stimulation.