Document Detail


Cocaethylene's effects on coronary artery blood flow and cardiac function in a canine model.
MedLine Citation:
PMID:  12215047     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: 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.
Authors:
Lance D Wilson; Scott French
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of toxicology. Clinical toxicology     Volume:  40     ISSN:  0731-3810     ISO Abbreviation:  J. Toxicol. Clin. Toxicol.     Publication Date:  2002  
Date Detail:
Created Date:  2002-09-06     Completed Date:  2002-09-18     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8213460     Medline TA:  J Toxicol Clin Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  535-46     Citation Subset:  AIM; IM    
Affiliation:
Department of Emergency Medicine, MetroHealth Medical Center, Cleveland, Ohio 44109, USA. ldwilson@pol.net
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MeSH Terms
Descriptor/Qualifier:
Animals
Cocaine / analogs & derivatives*,  blood,  metabolism,  pharmacology*
Coronary Circulation / drug effects*
Dogs
Dopamine Uptake Inhibitors / blood,  metabolism,  pharmacology*
Dose-Response Relationship, Drug
Electrocardiography / drug effects*
Heart / drug effects
Hemodynamics / drug effects*
Infusions, Intravenous
Chemical
Reg. No./Substance:
0/Dopamine Uptake Inhibitors; 50-36-2/Cocaine; 529-38-4/cocaethylene

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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