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 bee n noted in both intact humans and isolated denervated perfused rat hea rts. The study was designed to determine the effects of aging on intra cardiac conduction and pharmacodynamic responses to verapamil, and als o 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, nin e young (aged 3-4 years: 12.3 +/- 2.4 kg; 5 female, four male) and nin e senescent (aged 8-11 years: 12.0 +/- 2.2 kg; 5 female, four male) be agles 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 A V Wenckebach block cycle length (p < .0001) and decreased blood pressu re (p < .001) without age-related differences in responses. After auto nomic blockade, heart rate and blood pressure decreased (p < .0001) an d AV conduction intervals (p < .05) and AV Wenckebach block cycle leng th increased (p < .006). A-A intervals, A-H intervals, and AV Wenckeba ch 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). Verap amil effects on heart rate (p < .001) and AV conduction intervals (p < .007) and diastolic blood pressure (p < .003) were enhanced in younge r, but not senescent, beagles after propranolol and atropine. Discussi on. Verapamil produced similar effects on heart rate, blood pressure, and AV conduction in young and senescent beagles during barbiturate an esthesia. After double pharmacologic autonomic blockade, heart rate an d AV conduction intervals and AV Wenckebach cycle length were signific antly longer in senescent beagles when compared to younger beagles. Re sponses to verapamil after pharmacologic double autonomic blockade wer e enhanced only in younger beagles, suggesting greater contribution of reflex responses to results during verapamil infusions in the nonbloc ked state in younger animals.