Influence of autonomic blockade and aging on AV conduction and responses to verapamil in the beagle.
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.


CONCLUSIONS
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.
Schwartz
J B
JB
Department of Medicine, University of California, San Francisco.
Shen
C
C
Garcia
J
J
Capili
H
H
Sniezek
M
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects* / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006327:Heart Block / Q000139:chemically induced / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D014700:Verapamil / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D001285:Atropine; D011433:Propranolol; D014700:Verapamil; D010424:Pentobarbital