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. The test was repeated after cocaine HCl (1.0 mg/kg). Cocaine significantly (P < .01) increased heart rate, left ventricular systolic pressure and positive left ventricular dP/dt, as well as elicited VF in 34 animals. The cocaine exercise plus ischemia test was repeated in animals after pretreatment with either the beta adrenergic receptor antagonist propranolol HCl (1.0 mg/kg, n = 14) or the alpha adrenergic receptor antagonist prazosin HCl (0.5 mg/kg, n = 15). Both propranolol and prazosin reduced the hemodynamic effects of cocaine and prevented VF in 12 of 14 and 12 of 15 animals, respectively. The studies were 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-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)
Billman
G E
GE
Department of Physiology, Ohio State University, Columbus.
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D011224:Prazosin / Q000627:therapeutic use; D011433:Propranolol / Q000627:therapeutic use; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000517:prevention & control*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D011433:Propranolol; D003042:Cocaine; D011224:Prazosin