Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 50, Issue 2 M83-M90, Copyright © 1995 by The Gerontological Society of America
Influence of autonomic blockade and aging on AV conduction and responses to verapamil in the beagle
JB Schwartz, C Shen, J Garcia, H Capili and M Sniezek
Department of Medicine, University of California, San Francisco.
BACKGROUND. Age-related differences in responses to verapamil have been
noted in both intact humans and isolated denervated perfused rat hearts.
The study was designed to determine the effects of aging on intracardiac
conduction and pharmacodynamic responses to verapamil, and also to
determine the potential role of autonomic responses in previously reported
age-related differences in responses to verapamil. METHODS. After stability
of measures was demonstrated in senescent animals, nine young (aged 3-4
years: 12.3 +/- 2.4 kg; 5 female, four male) and nine senescent (aged 8-11
years: 12.0 +/- 2.2 kg; 5 female, four male) beagles were randomized to
undergo 60-minute verapamil infusions during pentobarbital anesthesia alone
or after 1 mg/kg propranolol and 0.5 mg/kg atropine. RESULTS. In the
nonblocked state, verapamil increased A-A intervals (p < .001), P-R (p
< .001), A-H intervals (p < .001), and AV Wenckebach block cycle
length (p < .0001) and decreased blood pressure (p < .001) without
age-related differences in responses. After autonomic blockade, heart rate
and blood pressure decreased (p < .0001) and AV conduction intervals (p
< .05) and AV Wenckebach block cycle length increased (p < .006). A-A
intervals, A-H intervals, and AV Wenckebach block cycle length were
significantly longer in senescent vs young beagles (559 +/- 87 vs 471 +/-
42 msec, p < .002; 103 +/- 6 vs 89 +/- 14, p < .05), 273 +/- 21 vs
238 +/- 26, p < .006, respectively). Verapamil effects on heart rate (p
< .001) and AV conduction intervals (p < .007) and diastolic blood
pressure (p < .003) were enhanced in younger, but not senescent, beagles
after propranolol and atropine. DISCUSSION. Verapamil produced similar
effects on heart rate, blood pressure, and AV conduction in young and
senescent beagles during barbiturate anesthesia. After double pharmacologic
autonomic blockade, heart rate and AV conduction intervals and AV
Wenckebach cycle length were significantly longer in senescent beagles when
compared to younger beagles. Responses to verapamil after pharmacologic
double autonomic blockade were enhanced only in younger beagles, suggesting
greater contribution of reflex responses to results during verapamil
infusions in the nonblocked state in younger animals.
