THE EFFECT OF ADRENERGIC-RECEPTOR ANTAGONISTS ON COCAINE-INDUCED VENTRICULAR-FIBRILLATION - ALPHA-ADRENERGIC-RECEPTOR BUT NOT BETA-ADRENERGIC-RECEPTOR ANTAGONISTS PREVENT MALIGNANT ARRHYTHMIAS INDEPENDENT

Cocaine-induced increases in catecholamines and the resulting enhanced activation of myocardial adrenergic receptors could contribute signif icantly 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 a nimals were selected in which this test failed to provoke ventricular arrhythmias. The test was repeated after cocaine HCl (1.0 mg/kg). Coca ine significantly (P <.01) increased heart rate, left ventricular syst olic pressure and positive left ventricular dP/dt, as well as elicited VF in 34 animals. The cocaine exercise plus ischemia test was repeate d in animals after pretreatment with either the beta adrenergic recept or antagonist propranolol HCl (1.0 mg/kg, n = 14) or the alpha adrener gic receptor antagonist prazosin HCl (0.5 mg/kg, n = 15). Both propran olol and prazosin reduced the hemodynamic effects of cocaine and preve nted VF in 12 of 14 and 12 of 15 animals, respectively. The studies we re then repeated with heart rate matched to the cocaine heart rate by ventricular pacing. Prazosin (n = 5) but not propranolol (n = 4) still prevented VF even with heart rate held constant. Finally, the alpha-1 A adrenergic receptor subtype antagonist WB4101 (2.0 mg/kg, n = 10) al so prevented cocaine VF in 7 of 10 animals without changing heart rate . In contrast, the alpha-1B adrenergic receptor antagonist chloroethyl clonidine (2.0 mg/kg, n = 3) failed to prevent VF. Thus, alpha but not beta adrenergic receptor antagonists can prevent cocaine-induced mali gnant arrhythmias independently of their action on heart rate. These d ata suggest that enhanced activation of alpha adrenergic receptors (pa rticularly the alpha-1A subtype) may contribute significantly to cocai ne-induced VF.