Ld. Wilson et al., Cocaine, ethanol, and cocaethylelae cardiotoxity in an animal model of cocaine and ethanol abuse, ACAD EM MED, 8(3), 2001, pp. 211-222
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.