Direct myocardial effects of cocaine.
OBJECTIVE
The aim was to determine whether cocaine has a direct effect on the myocardium which is independent of coronary vasospasm.


METHODS
Cocaine was introduced into the perfusate of the isolated rabbit ventricular septal preparation in the concentration range 10(-5) to 10(-3)M while holding coronary flow of oxygenated Krebs solution constant at 3.0 ml.min-1 by a perfusion pump. The septa were obtained from white male New Zealand rabbits and were paced at 48 beats.min-1. Mechanical and enzymatic measurements were performed.


RESULTS
Developed tension (T), maximum contraction velocity (+dT/dt), and maximum relaxation velocity (-dT/dt) were all depressed to approximately the same degree at each different cocaine concentration and averaged 4, 48, and 95% at 10(-5), 10(-4), and 10(-3)M cocaine respectively, with an ED50 = 9 x 10(-5)M. Relaxation time (tR/T) was prolonged, but the ED50 was greater (by 1.5 times) than for the other mechanical parameters. Simultaneously, an increase in excitation threshold dysrhythmia developed which resulted in 17, 50, and 90 beats missed per 100 stimulations at 10(-5), 10(-4), and 10(-3)M cocaine respectively. Resting tension (RT) was not altered. Coronary flow rate was not reduced in presence of cocaine because of the constant delivery pump. T, +dT/dt, -dT/dt and modulation of the excitation threshold completely recovered after washout of cocaine.


CONCLUSIONS
Cocaine has acute direct, though reversible, depressant effects on the myocardium, including depression of function and modulation of excitation threshold, which are independent of its effect on coronary flow.
Morcos
N C
NC
University of California, Irvine 91717.
Fairhurst
A
A
Henry
W L
WL
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003402:Creatine Kinase / Q000187:drug effects; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology; D011817:Rabbits
D007773:Lactates; D019344:Lactic Acid; D003402:Creatine Kinase; D003042:Cocaine