Document Detail

Electrophysiological effects of high cocaine concentrations on intact canine heart. Evidence for modulation by both heart rate and autonomic nervous system.
MedLine Citation:
PMID:  8443914     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Previous clinical reports have suggested that cocaine intoxication may produce severe ventricular arrhythmias due to a direct effect on the heart. However, the effects of high plasma levels of cocaine on the electrophysiology of the heart have not been well characterized and remain poorly understood. METHODS AND RESULTS: The purpose of this study was to characterize the electrophysiological effects of high doses of cocaine on the in situ dog heart. In dogs anesthetized with morphine and alpha-chloralose, cocaine (2-11 micrograms/mL) increased both atrial and ventricular refractory periods and produced rate-dependent increases in atrial, atrioventricular, His-Purkinje, and ventricular conduction intervals. The time constant for the onset of cocaine's conduction slowing effect following a reduction in pacing cycle length from 400 to 260 msec was approximately two beats, and the time constant for diastolic recovery from conduction slowing was approximately 200 msec, which are similar to values reported for several class Ib antiarrhythmic drugs. Cocaine produced a rate-dependent increase in QT interval that was greatest at high heart rates yet produced no change in the ST (QT-QRS) interval. This suggests that high plasma levels of cocaine delay repolarization primarily via slowing of conduction. Cocaine's effects on both atrioventricular and intraventricular conduction were significantly larger in autonomically blocked than in autonomically intact animals. CONCLUSIONS: We conclude that high plasma levels of cocaine, similar to those reported in autopsy reports following fatal cocaine overdose in humans, produce significant rate-dependent conduction slowing effects on atrial, atrioventricular, and ventricular conduction in the in situ heart. These rate-dependent effects are intensified following autonomic blockade.
C W Clarkson; C Chang; A Stolfi; W J George; S Yamasaki; A S Pickoff
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  87     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1993 Mar 
Date Detail:
Created Date:  1993-04-06     Completed Date:  1993-04-06     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  950-62     Citation Subset:  AIM; IM    
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112-2699.
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MeSH Terms
Arrhythmias, Cardiac / etiology
Autonomic Nervous System / physiology*
Bundle of His / physiology
Cardiac Pacing, Artificial
Cocaine / pharmacology*
Coronary Circulation
Dose-Response Relationship, Drug
Heart / drug effects*,  physiology
Heart Conduction System / drug effects
Heart Rate / physiology*
Osmolar Concentration
Refractory Period, Electrophysiological
Grant Support
Reg. No./Substance:
Comment In:
Circulation. 1993 Mar;87(3):1046-7   [PMID:  8443884 ]

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