COCAINE-ENHANCED ARRHYTHMOGENESIS - NEURAL AND NONNEURAL MECHANISMS

Cocaine abuse increases the susceptibility to cardiovascular complicat ions and sudden cardiac death in man. We used programmed electrical st imulation of the heart to examine the arrhythmogenic influence of coca ine. Twenty-three pentobarbital-anesthetized adult dogs underwent prog rammed electrical stimulation using one to four extrastimuli before an d during cocaine infusion. Autonomic decentralization was performed pr ior to the protocol in eight dogs. Induced ventricular arrhythmias inc luded single premature ventricular depolarizations, doublets, triplets , ventricular tachycardia, and ventricular fibrillation. Intravenous c ocaine, and subsequent adrenergic and muscarinic receptor blockade, or calcium channel blockade were evaluated for their influence on arrhyt hmogenesis. The incidence of induced ventricular arrhythmias was signi ficantly elevated following cocaine and was reduced following proprano lol and atropine. Verapamil, however, did not reduce the incidence of induced arrhythmias. In addition, cocaine significantly increased arrh ythmia induction in decentralized animals, but propranolol, atropine, and phentolamine failed to reduce the proarrhythmic effects of cocaine in these animals. Thus, cocaine has a proarrhythmic effect on the hea rt with multiple mechanisms. The adrenergic mechanism appears to be a result of neurotransmitter uptake blockade, whereas the likely ionic m echanism is a neurally independent, direct effect on the heart.