Document Detail

U74006F, a novel 21-aminosteroid, inhibits in vivo lipid peroxidation but fails to limit infarct size in a canine model of myocardial ischemia reperfusion.
MedLine Citation:
PMID:  1877444     Owner:  NLM     Status:  MEDLINE    
Peroxidation of membrane lipids has been suggested to play a role in the pathogenesis of myocardial ischemia/reperfusion injury. We therefore assessed the efficacy of U74006F, a potent in vitro vitamin E-like inhibitor of lipid peroxidation, in limiting infarct size in a canine model of transient coronary artery occlusion. Twenty dogs underwent 2 hours of occlusion of the left anterior descending coronary artery and 6 hours of reperfusion. U74006F or saline solution was administered continuously from 1 hour of occlusion to the end of the experiment. U74006F blunted any increase in production of conjugated dienes (an index of lipid peroxidation) at both 30 minutes (1.73 +/- 0.16 mol/L x 10(-4) vs 2.62 +/- 0.22 in control dogs, p less than 0.05) and 6 hours (1.39 +/- 0.22 vs 2.06 +/- 0.18 in control dogs, p less than 0.05) after reperfusion. Furthermore, 6 hours after reflow vitamin E levels tended to be lower than baseline values in control dogs and higher than baseline values in dogs treated with U74006F. However, analysis of infarct size indicated no statistically significant difference between the two groups when expressed either as a percentage of the left ventricle (10.4 +/- 1.8% in U74006F vs 15.2 +/- 2.4% in control dogs) or as a percentage of the area at risk (33.0 +/- 5.5% in U74006F vs 37.8 +/- 4.5% in control dogs). Although U74006F appeared to be a potent in vivo inhibitor of lipid peroxidation, it failed to limit infarct size after 2 hours of occlusion and 6 hours of reperfusion in this canine model.
M Ovize; M de Lorgeril; A Ovize; M Ciavatti; J Delaye; S Renaud
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American heart journal     Volume:  122     ISSN:  0002-8703     ISO Abbreviation:  Am. Heart J.     Publication Date:  1991 Sep 
Date Detail:
Created Date:  1991-09-26     Completed Date:  1991-09-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370465     Medline TA:  Am Heart J     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  681-9     Citation Subset:  AIM; IM    
INSERM Unit 63, Lyon, France.
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MeSH Terms
Hemodynamics / drug effects
Leukocyte Count
Lipid Peroxides / antagonists & inhibitors*
Myocardial Infarction / blood,  drug therapy*,  pathology
Myocardial Reperfusion Injury / prevention & control*
Myocardium / pathology
Pregnatrienes / therapeutic use*
Time Factors
Vitamin E / blood
Reg. No./Substance:
0/Lipid Peroxides; 0/Pregnatrienes; 110101-67-2/tirilazad; 1406-18-4/Vitamin E

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

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