Document Detail

Glucose oxidation is stimulated in reperfused ischemic hearts with the carnitine palmitoyltransferase 1 inhibitor, Etomoxir.
MedLine Citation:
PMID:  2779537     Owner:  NLM     Status:  MEDLINE    
The effect of the carnitine palmitoyltransferase 1 (CPT 1) inhibitor, Etomoxir, on glucose oxidation rates was determined in ischemic hearts reperfused in the presence of fatty acids. Isolated working rat hearts were perfused with 11 mM (14C)-glucose and 1.2 mM palmitate at a 15 cm H2O preload, 80 mm Hg afterload. Hearts were subjected to either 60 min aerobic perfusion, or 15 min work followed by 25 min global ischemia then 60 min of aerobic reperfusion. Steady state glucose oxidation rates in reperfused ischemic hearts were not significantly different from non-ischemic hearts. If 10(-9) M Etomoxir was added immediately prior to reperfusion no significant change in glucose oxidation occurred. Addition of 10(-8) M and 10(-6) M Etomoxir, however, significantly increased glucose oxidation. Etomoxir also significantly improved recovery of mechanical function at a concentration of 10(-8) M or greater. As we previously reported, no significant improvement of function was seen when 10(-9) M Etomoxir was added to the perfusate (Lopaschuk GD et al., Circ Res 63: 1036-1043, 1988). Long chain acylcarnitine levels were significantly reduced in the presence of both 10(-9) M and 10(-8) M Etomoxir. These data demonstrate that the beneficial effect of Etomoxir on reperfusion recovery of ischemic hearts is not due to a lowering of long chain acylcarnitine levels. Etomoxir may improve recovery of function by overcoming fatty acid inhibition of glucose oxidation.
G D Lopaschuk; G F McNeil; J J McVeigh
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  88     ISSN:  0300-8177     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:    1989 Jun 27-Jul 24
Date Detail:
Created Date:  1989-10-26     Completed Date:  1989-10-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  175-9     Citation Subset:  IM    
Department of Pediatrics, Faculty of Medicine, University of Alberta, Edmonton, Canada.
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MeSH Terms
Acyltransferases / antagonists & inhibitors*
Carnitine / analogs & derivatives,  metabolism
Carnitine O-Palmitoyltransferase / antagonists & inhibitors*
Epoxy Compounds / pharmacology*
Ethers, Cyclic / pharmacology*
Glucose / metabolism*
Myocardial Reperfusion Injury / metabolism,  prevention & control*
Myocardium / metabolism*
Palmitates / metabolism
Rats, Inbred Strains
Reg. No./Substance:
0/Epoxy Compounds; 0/Ethers, Cyclic; 0/Palmitates; 50-99-7/Glucose; 541-15-1/Carnitine; 82258-36-4/etomoxir; EC 2.3.-/Acyltransferases; EC O-Palmitoyltransferase

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