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Research Article

Cocaethylene's Effects on Coronary Artery Blood Flow and Cardiac Function in a Canine Model

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Pages 535-546 | Published online: 08 Jan 2002
 

Abstract

Objectives: Cocaethylene is a toxic metabolite of cocaine formed in the presence of ethanol. Though cocaine causes coronary vasoconstriction, cocaethylene's effects on coronary flow are unknown. The aim of our study was to describe cocaethylene's effects on coronary flow and cardiac function. Methods: Sixteen alpha-chloralose anesthetized dogs were monitored with Swan-Ganz, arterial and venous catheters, and an electrocardiogram. Doppler flow probes were placed on the circumflex and left anterior descending coronary arteries. Dogs were allotted 15 mg/kg (n=10) or 30 mg/kg (n=6) of cocaethylene given as a continuous intravenous infusion. Measurements were made at fixed time intervals during the 60-minute cocaethylene infusion and 2-hour observation period. Results: The cocaethylene concentrations were maximal at the end of the infusion and cocaethylene was rapidly metabolized to benzoylecognine. One low-dose animal died of ventricular fibrillation. Five high-dose dogs experienced ventricular arrhythmias or pulseless electrical activity (PEA), and three died. In the low-dose group, cocaethylene caused a 38% increase in mean arterial pressure relative to baseline, and increased systemic vascular resistance. In the high-dose group, at maximal cocaethylene concentrations, stroke volume decreased by 42% (p<0.0002), and circumflex blood flow decreased by 30% (p=0.03) relative to baseline, when arrhythmias occurred. The PR, QRS, and QTc intervals increased by 48, 209, and 29%, respectively (p<0.001). As cocaethylene levels declined, circumflex blood flow increased by 77% (p=0.05) and mean arterial pressure increased 49% (p<0.01), also relative to baseline. Conclusions: Cocaethylene caused hypertension and increased systemic vascular resistance. At high concentrations, it decreased myocardial function, slowed cardiac conduction, and was arrhythmogenic. The cocaethylene's toxicity does not appear to be mediated by effects on coronary blood flow.

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