Electrophysiological effects of high cocaine concentrations on intact canine heart. Evidence for modulation by both heart rate and autonomic nervous system.
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.


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.
Clarkson
C W
CW
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112-2699.
Chang
C
C
Stolfi
A
A
George
W J
WJ
Yamasaki
S
S
Pickoff
A S
AS
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D001341:Autonomic Nervous System / Q000502:physiology*; D002036:Bundle of His / Q000502:physiology; D002304:Cardiac Pacing, Artificial; D003042:Cocaine / Q000494:pharmacology*; D003326:Coronary Circulation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000502:physiology*; D006439:Hemodynamics; D008297:Male; D009994:Osmolar Concentration; D012032:Refractory Period, Electrophysiological
D003042:Cocaine