Document Detail


Effects of dichloroacetate on mechanical recovery and oxidation of physiologic substrates after ischemia and reperfusion in the isolated heart.
MedLine Citation:
PMID:  9514176     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of dichloroacetate (DCA) on fatty acid oxidation and flux through pyruvate dehydrogenase (PDH) were studied in ischemic, reperfused myocardium supplied with glucose, long-chain fatty acids, lactate, pyruvate, and acetoacetate. The oxidation rates of all substrates were determined by combined 13C nuclear magnetic resonance (NMR) spectroscopy and oxygen-consumption measurements, and PDH flux was assessed by lactate plus pyruvate oxidation. In nonischemic control hearts, DCA increased PDH flux more than eightfold (from 0.68 +/- 0.28 to 5.81 +/- 1.16 micromol/min/g dry weight; n = 8 each group; p < 0.05) and significantly inhibited the oxidation of acetoacetate and fatty acids. DCA also improved mechanical recovery after 30 min of ischemia plus 30 min of reperfusion but did not significantly increase PDH flux measured at the end of the reperfusion period (1.35 +/- 0.42 micromol/min/g dry weight) compared with untreated ischemic hearts (0.87 +/- 0.28 micromol/min/g dry weight; n = 8 each group; p = NS). Although DCA had a modest effect on functional recovery in the reperfused myocardium, this beneficial effect was not associated with either marked stimulation of PDH flux or inhibition of fatty acid oxidation.
Authors:
C Barak; M K Reed; S P Maniscalco; A D Sherry; C R Malloy; M E Jessen
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  31     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-04-16     Completed Date:  1998-04-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  336-44     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Texas Southwestern Medical Center at Dallas, 75235-8879, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetoacetates / metabolism
Animals
Dichloroacetate / pharmacology*
Fatty Acids / metabolism
Glucose / metabolism
Heart / drug effects*,  physiopathology
Lactates / metabolism
Magnetic Resonance Spectroscopy
Male
Myocardial Ischemia / metabolism,  physiopathology*
Myocardial Reperfusion Injury / metabolism,  physiopathology*
Oxidation-Reduction
Oxygen / metabolism
Pyruvic Acid / metabolism
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
RR02584/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Acetoacetates; 0/Fatty Acids; 0/Lactates; 127-17-3/Pyruvic Acid; 13425-80-4/Dichloroacetate; 50-99-7/Glucose; 541-50-4/acetoacetic acid; 7782-44-7/Oxygen

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


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