Alpha-adrenergic influences in canine ischemic sudden death: effects of alpha 1-adrenoceptor blockade with prazosin.
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.
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D004285:Dogs; D004594:Electrophysiology; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000401:mortality* / Q000503:physiopathology; D011224:Prazosin / Q000627:therapeutic use*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013610:Tachycardia / Q000188:drug therapy
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D011224:Prazosin