Cocaine, ethanol, and cocaethylelae cardiotoxity in an animal model of cocaine and ethanol abuse

Objectives: Simultaneous abuse of cocaine and ethanol affects 12 million Am ericans annually. In combination, these substances are substantially more t oxic than either drug alone. Their combined cardiac toxicity may be due to independent effects of each drug; however, they may also be due to cocaethy lene (CE), a cocaine metabolite formed only in the presence of ethanol. The purpose of this study was to delineate the role of CE in the combined card iotoxicity of cocaine and ethanol in a model simulating their abuse. Method s: Twenty-three dogs were randomized to receive either 1) three intravenous (IV) boluses of cocaine 7.5 mg/kg with ethanol (1 g/kg) as an IV infusion (C+E, n = 8), 2) three cocaine boluses only (C, n = 6), 3) ethanol infusion only (E, n = 5), or 4) placebo boluses and infusion (n = 4). Hemodynamic m easurements, electrocardiograms, and serum drug concentrations were obtaine d at baseline, and then at fixed time intervals after each drug was adminis tered. Results: Two of eight dogs in the C+E group experienced cardiovascul ar collapse. The most dramatic hemodynamic changes occurred after each coca ine bolus in the C+E and C only groups; however, persistent hemodynamic cha nges occurred in the C+E group. Peak CE levels were associated with a 45% ( SD +/- 22%, 95% CI = 22% to 69%) decrease in cardiac output (p < 0.05), a 5 6% (SD +/- 23%, 95% CI = 32% to 80%) decrease in dP/dt(max) (p < .006), and a 23% (SD +/- 15%, 95% CI = 7% to 49%) decrease in SVO2 (p < 0.025). Ventr icular arrhythmias were primarily observed in the C+E group, in which four of eight dogs experienced ventricular tachycardia. Conclusions: Cocaine and ethanol in combination were more toxic than either substance alone. Go-adm inistration resulted in prolonged cardiac toxicity and was dysrhythmogenic. Peak serum cocaethylene concentrations were associated with prolonged myoc ardial depression.