Cocaine-enhanced arrhythmogenesis: neural and nonneural mechanisms.
Cocaine abuse increases the susceptibility to cardiovascular complications and sudden cardiac death in man. We used programmed electrical stimulation of the heart to examine the arrhythmogenic influence of cocaine. Twenty-three pentobarbital-anesthetized adult dogs underwent programmed electrical stimulation using one to four extrastimuli before and during cocaine infusion. Autonomic decentralization was performed prior to the protocol in eight dogs. Induced ventricular arrhythmias included single premature ventricular depolarizations, doublets, triplets, ventricular tachycardia, and ventricular fibrillation. Intravenous cocaine, and subsequent adrenergic and muscarinic receptor blockade, or calcium channel blockade were evaluated for their influence on arrhythmogenesis. The incidence of induced ventricular arrhythmias was significantly elevated following cocaine and was reduced following propranolol and atropine. Verapamil, however, did not reduce the incidence of induced arrhythmias. In addition, cocaine significantly increased arrhythmia 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 heart with multiple mechanisms. The adrenergic mechanism appears to be a result of neurotransmitter uptake blockade, whereas the likely ionic mechanism is a neurally independent, direct effect on the heart.
Gantenberg
N S
NS
Department of Physiology and Biophysics, University of Alabama, Birmingham 35294.
Hageman
G R
GR
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000294:innervation / Q000502:physiology; D008297:Male; D018727:Muscarinic Antagonists; D009474:Neurons / Q000502:physiology*; D010276:Parasympatholytics / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D003042:Cocaine