Alpha-adrenergic influences in canine ischemic sudden death: effects of alpha 1-adrenoceptor blockade with prazosin

Abstract

The antiarrhythmic and antifibrillatory actions of the alpha 1-adrenoceptor 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 micrograms/kg and the higher multiple dose administration of 500 micrograms/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 less than 0.05) in animals pretreated with 100 micrograms/kg prazosin and 3 of 8 (37%, p less than 0.05) in animals pretreated with 500 micrograms/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 postinfarction dogs relative to the vehicle group [24-h survival: 1 of 16 (6%) vehicle v 4 of 8 (50%) in higher dose prazosin group, p less than 0.05]. These findings suggest that the blockade of alpha 1-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 postinfarction setting.