The Journal of pharmacology and experimental therapeutics
-
J. Pharmacol. Exp. Ther. · Apr 1994
The effect of adrenergic receptor antagonists on cocaine-induced ventricular fibrillation: alpha but not beta adrenergic receptor antagonists prevent malignant arrhythmias independent of heart rate.
Cocaine-induced increases in catecholamines and the resulting enhanced activation of myocardial adrenergic receptors could contribute significantly to the formation of ventricular fibrillation (VF). In order to test this hypothesis, a 2-min coronary occlusion was initiated during the last minute of exercise in instrumented mongrel dogs. Forty-one animals were selected in which this test failed to provoke ventricular arrhythmias. ⋯ Finally, the alpha-1A adrenergic receptor subtype antagonist WB4101 (2.0 mg/kg, n = 10) also prevented cocaine VF in 7 of 10 animals without changing heart rate. In contrast, the alpha-1B adrenergic receptor antagonist chloroethylclonidine (2.0 mg/kg, n = 3) failed to prevent VF. Thus, alpha but not beta adrenergic receptor antagonists can prevent cocaine-induced malignant arrhythmias independently of their action on heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)