Document Detail


Impact of low-flow ischemia on substrate oxidation and glycolysis in the isolated perfused rat heart.
MedLine Citation:
PMID:  15001444     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interventions that stimulate carbohydrate oxidation appear to be beneficial in the setting of myocardial ischemia or infarction. However, the mechanisms underlying this protective effect have not been defined, in part because of our limited understanding of substrate utilization under ischemic conditions. Therefore, we used (1)H and (13)C NMR spectroscopy to investigate substrate oxidation and glycolytic rates in a global low-flow model of myocardial ischemia. Isolated male Sprague-Dawley rat hearts were perfused for 30 min under conditions of normal flow (control) and low-flow ischemia (LFI, 0.3 ml/min) with insulin and (13)C-labeled lactate, pyruvate, palmitate, and glucose at concentrations representative of the physiological fed state. Despite a approximately 50-fold reduction in substrate delivery and oxygen consumption, oxidation of all exogenous substrates plus glycogen occurred during LFI. Oxidative metabolism accounted for 97% of total calculated ATP production in the control group and approximately 30% in the LFI group. For controls, lactate oxidation was the major source of ATP; however, in LFI, this shifted to a combination of oxidative and nonoxidative glycogen metabolism. Interestingly, in the LFI group, anaplerosis relative to citrate synthase increased sevenfold compared with controls. These results demonstrate the importance of oxidative energy metabolism for ATP production, even during very-low-flow ischemia. We believe that the approach described here will be valuable for future investigations into the underlying mechanisms related to the protective effect of increasing cardiac carbohydrate utilization and may ultimately lead to identification of new therapeutic targets for treatment of myocardial ischemia.
Authors:
Steven G Lloyd; Peipei Wang; Huadong Zeng; John C Chatham
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-03-04
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  287     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-22     Completed Date:  2004-07-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H351-62     Citation Subset:  IM    
Affiliation:
Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, McCallum Bldg., Rm. 684 1530 3rd Ave. South, Birmingham, AL 35294-0005, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / biosynthesis
Animals
Coronary Circulation*
Energy Metabolism*
Glycolysis*
Heart / physiopathology
Male
Myocardial Ischemia / metabolism,  physiopathology*
Myocardium / metabolism*
Oxidation-Reduction
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
5T32 HL-07703/HL/NHLBI NIH HHS; CA-13148/CA/NCI NIH HHS; HL-48789/HL/NHLBI NIH HHS; HL-67464/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
56-65-5/Adenosine Triphosphate

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


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