Effects of acute and chronic administration of acebutolol on the right ventricular effective refractory period in conscious dogs.
beta-Adrenergic blocking drugs are effective in reducing sudden cardiac death after acute myocardial infarction but the precise mechanism of this effect is unclear. We investigated the acute and chronic effects of acebutolol, a beta-adrenergic blocker, on electrocardiographic parameters, diastolic excitability threshold (DET), and right ventricular effective refractory period (RVERP) in chronically instrumented conscious dogs. These parameters were determined during spontaneous sinus rhythm and at a fixed pacing rate (200 beats/min). Acebutolol (0.5, 1, and 5 mg/kg i.v.) decreased the heart rate (HR) (by 23, 26, and 24%, respectively) without effects on any electrocardiographic parameters or on the DET. The maximal increases in ERP were 4.7, 7, and 7.8%, respectively, during pacing and 8.5, 13.3, and 10.3%, respectively, during sinus rhythm. Acebutolol, 10 mg/kg/day P.O. for 6 weeks, reduced the HR from the third day onward without altering the PR, QRS, QT, or QTc intervals or the DET. The increase in ERP was significant from the third day (14%) during pacing and from the seventh day (15.5%) during sinus rhythm. The degree of prolongation of the ERP subsequently remained stable during the 6 weeks of treatment. The ERP returned to the baseline value 7 days after acebutolol withdrawal. This increase in ERP, which was more marked during chronic oral treatment, could contribute to the documented protective effect of the beta-blocking drugs against sudden cardiac death after myocardial infarction.
Vincent
A
A
Laboratoire de Pharmacologie, Faculté de Médecine, Lille, France.
Werquin
S
S
Caron
J
J
Libersa
C
C
Fautrez
V
V
Dupuis
B
B
D000070:Acebutolol / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D016278:Ventricular Function, Right / Q000187:drug effects*
D000070:Acebutolol