Persistent left ventricular dysfunction after cocaine treatment in rabbits.
The present study was undertaken to determine whether the diminished cardiac performance associated with cocaine administration persists after the drug has been eliminated from the body. Cocaine (5 or 10 mg/kg iv) was administered to conscious (n = 7) or pentobarbital-anesthetized (n = 7) rabbits, respectively. Seven conscious and seven anesthetized control rabbits received the saline vehicle. Two and one-half hours later, the hearts were removed from the animals and perfused under cocaine-free conditions. Left ventricular (LV) contractility was evaluated by plotting steady-state LV systolic and diastolic pressures as a function of LV end-diastolic volume (preload). LV systolic performance was diminished in a dose-related manner in hearts isolated from cocaine-treated rabbits, but was statistically different from control only at the higher cocaine dose (P < 0.05). In a second set of experiments, hearts (n = 6) were isolated, and their LV function was evaluated before, during, and after cocaine exposure. In these experiments, cocaine was added to the perfusate in increments to produce concentrations of 5, 10, and 15 mg/liter. After LV function was evaluated at the highest cocaine dose, cocaine-free perfusion conditions were restored, and LV function was reevaluated. In these experiments, cocaine produced a dose-dependent decrease in LV function that readily reversed when cocaine-free perfusion was reinstated. We conclude that cocaine diminishes LV contractility, and that the diminished cardiac performance may not readily reverse after in vivo exposure. Moreover, the rapid restoration of cardiac performance after exposure to cocaine in vitro suggests that the mechanism operating in vivo involves more than a simple direct action on the myocyte. Catecholamine cardiotoxicity does not appear to be a primary factor.
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Department of Physiology, Northeastern Ohio Universities College of Medicine, Rootstown 44272.
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D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011817:Rabbits; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
D003042:Cocaine; D009638:Norepinephrine; D004837:Epinephrine