Ns. Gantenberg et Gr. Hageman, COCAINE-ENHANCED ARRHYTHMOGENESIS - NEURAL AND NONNEURAL MECHANISMS, Canadian journal of physiology and pharmacology, 70(2), 1992, pp. 240-246
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.