PERSISTENT LEFT-VENTRICULAR DYSFUNCTION AFTER COCAINE TREATMENT IN RABBITS

The present study was undertaken to determine whether the diminished c ardiac performance associated with cocaine administration persists aft er the drug has been eliminated from the body. Cocaine (5 or 10 mg/kg iv) was administered to conscious (n = 7) or pentobarbital-anesthetize d (n = 7) rabbits, respectively. Seven conscious and seven anesthetize d control rabbits received the saline vehicle. Two and one-half hours later, the hearts were removed from the animals and perfused under coc aine-free conditions. Left ventricular (LV) contractility was evaluate d by plotting steady-state LV systolic and diastolic pressures as a fu nction of LV end-diastolic volume (preload). LV systolic performance w as 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, h earts (n = 6) were isolated, and their LV function was evaluated befor e, during, and after cocaine exposure. In these experiments, cocaine w as 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 dos e-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 re adily reverse after in vivo exposure. Moreover, the rapid restoration of cardiac performance after exposure to cocaine in vitro suggests tha t the mechanism operating in vivo involves more than a simple direct a ction on the myocyte. Catecholamine cardiotoxicity does not appear to be a primary factor.