Cocaethylene's effects on coronary artery blood flow and cardiac function in a canine model.
OBJECTIVE
Cocaethylene is a toxic metabolite of cocaine formed in the presence of ethanol. Though cocaine causes coronary vasoconstriction, cocaethylene's effects on coronaryflow 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. Dopplerflow probes were placed on the circumflex and left anterior descending coronary arteries. Dogs were allotted 15 mg/kg (n = 10) or 30mg/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.
Wilson
Lance D
LD
Department of Emergency Medicine, MetroHealth Medical Center, Cleveland, Ohio 44109, USA. ldwilson@pol.net
French
Scott
S
D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D018765:Dopamine Uptake Inhibitors / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous
D018765:Dopamine Uptake Inhibitors; C066444:cocaethylene; D003042:Cocaine