α-Adrenergic Influences in Canine Ischemic Sudden Death

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Abstract
The antiarrhythmic and antifibrillatory actions of the α1-adrenoeeptor antagonist prazosin were evaluated in conscious dogs 4–7 days after anterior myocardial infarction. Both the intravenous (i.v.) low single dose administration of 100 μg/kg and the higher multiple dose administration of 500 μg/kg every 6 h for 24 h failed to alter electrocardiographic intervals, ventricular effective refractory periods, or the induction of ventricular tachycardia (VT) by programmed ventricular stimulation. During the first 30 min of a subsequent episode of acute posterolateral ischemia, the incidence of ventricular fibrillation (VF) was reduced from 13 of 16 (81%) in vehicle-pretreated control animals to 2 of 8 (25%. p < 0.05) in animals pretreated with 100 μg/kg prazosin and 3 of 8 (37%. p < 0.05) in animals pretreated with 500 μ-g/kg prazosin every 6 h for 24 h. The continued administration of prazosin in the higher dose regimen, every 6 h for 24 h. significantly enhanced survival at 24 h after the onset of posterolateral ischemia in postinfaretion dogs relative to the vehicle group [24-h survival: 1 of 16 (6%) vehicle r 4 of 8 (50%) in higher dose prazosin group, p < 0.05]. These findings suggest that the blockade of α1-adrenoceptor stimulation may be efficacious in preventing lethal ventricular arrhythmias associated with acute ischemia, despite the lack of effect on electrophysiologic parameters and induction of VT in the postinfaretion setting.

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