Cocaine Plus Ethanol is More Cardiotoxic Than Cocaine or Ethanol Alone

Objectives: The purpose of this study was to determine the hemodynamic effects of recreational/toxic doses of ethanol, or cocaine, or ethanol followed by cocaine.

Design: Prospective, randomized study.

Setting: University research laboratory.

Subjects: Eighteen healthy, adult mongrel dogs.

Interventions: Dogs were randomized to receive ethanol (1 g/kg iv) over 20 mins and a 10-mL bolus of 0.9% sodium chloride, or 5% dextrose in water, over 20 mins, and then a cocaine bolus (7.5 mg/kg), or ethanol (1 g/kg iv), over 20 mins, and then a cocaine bolus (7.5 mg/kg).

Measurements And Main Results: Arterial, left ventricular, and pulmonary arterial pressures, mixed venous blood oxygen saturation, and heart rate (HR) were continuously recorded in each dog. The maximal rate of left ventricular pressure increase (dP/dtmax) and decrease (dP/dtmin), stroke volume, HR, pulmonary artery occlusion pressure (PAOP), and plasma concentrations of ethanol and cocaine were measured at baseline, after ethanol or placebo infusions, and then after a cocaine or placebo bolus at specific time intervals over a 5-hr study period. The plasma ethanol concentration increased to 160 +/- 8 mg/dL at 30 mins after the start of the infusion, and then decreased to 30 +/- 8 mg/dL at 180 mins. The plasma cocaine concentration increased to 4587 +/- 383 ng/mL within 2 mins of the bolus injection, and then decreased and approached the baseline at 240 mins. Immediately after injection, ethanol plus cocaine synergistically decreased dP/dtmax by 70% and dP/dtmin by 81% (both p < .001). In addition, immediately after injection, ethanol plus cocaine maximally decreased the stroke volume by 34% (p < .05) and maximally increased the HR by 89% and PAOP by 127% (both p < .002). The dP/dtmax and the stroke volume remained decreased by 15% to 20% for 5 hrs (p < .05). Cocaine alone, immediately after injection, maximally decreased dP/dtmax and dP/dtmin by 40% (p < .02), and caused a 26% decrease in stroke volume (p = .05), a 48% increase in HR (p < .02), and a 75% increase in PAOP. The decrease in dP/dtmax persisted for approximately 60 to 90 mins. Ethanol alone produced transient 6% to 13% decreases in dP/dtmax, dP/dtmin, and stroke volume (NS) and small (9%) increases in the HR (NS) during the first hour after injection.

Conclusion: Cocaine combined with ethanol produces a significant synergistic depression of ventricular contraction and relaxation that substantially exceeds the arithmetic sum of the depressive effects of either cocaine or ethanol alone.