Document Detail


Impact of anaerobic glycolysis and oxidative substrate selection on contractile function and mechanical efficiency during moderate severity ischemia.
MedLine Citation:
PMID:  18660443     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The role of anaerobic glycolysis and oxidative substrate selection on contractile function and mechanical efficiency during moderate severity myocardial ischemia is unclear. We hypothesize that 1) preventing anaerobic glycolysis worsens contractile function and mechanical efficiency and 2) increasing glycolysis and glucose oxidation while inhibiting free fatty acid oxidation improves contractile function during ischemia. Experiments were performed in anesthetized pigs, with regional ischemia induced by a 60% decrease in left anterior descending coronary artery blood flow for 40 min. Three groups were studied: 1) no treatment, 2) inhibition of glycolysis with iodoacetate (IAA), or 3) hyperinsulinemia and hyperglycemia (HI + HG). Glucose and free fatty acid oxidation were measured using radioisotopes and anaerobic glycolysis from net lactate efflux and myocardial lactate content. Regional contractile power was assessed from left ventricular pressure and segment length in the anterior wall. We found that preventing anaerobic glycolysis with IAA during ischemia in the absence of alterations in free fatty acid and glucose oxidation did not adversely affect contractile function or mechanical efficiency during myocardial ischemia, suggesting that anaerobic glycolysis is not essential for maintaining residual contractile function. Increasing glycolysis and glucose oxidation with HI + HG inhibited free fatty acid oxidation and improved contractile function and mechanical efficiency. In conclusion, these results show a dissociation between myocardial function and anaerobic glycolysis during moderate severity ischemia in vivo, suggesting that metabolic therapies should not be aimed at inhibiting anaerobic glycolysis per se, but rather activating insulin signaling and/or enhancing carbohydrate oxidation and/or decreasing fatty acid oxidation.
Authors:
Lufang Zhou; Hazel Huang; Tracy A McElfresh; Domenick A Prosdocimo; William C Stanley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-07-25
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  295     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-08     Completed Date:  2008-10-16     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H939-H945     Citation Subset:  IM    
Affiliation:
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
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MeSH Terms
Descriptor/Qualifier:
Anaerobiosis
Animals
Blood Gas Analysis
Blood Pressure / drug effects,  physiology
Coronary Circulation / drug effects,  physiology
Enzyme Inhibitors / pharmacology
Fatty Acids, Nonesterified / metabolism
Glucose / metabolism
Glycolysis / drug effects,  physiology*
Heart Rate / drug effects,  physiology
Hypoglycemic Agents / pharmacology
Insulin / blood,  pharmacology
Iodoacetates / pharmacology
Myocardial Contraction / physiology*
Myocardial Ischemia / metabolism*,  pathology,  physiopathology*
Oxidation-Reduction
Swine
Ventricular Function, Left / drug effects
Grant Support
ID/Acronym/Agency:
GM-66309/GM/NIGMS NIH HHS; HL-074237/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Fatty Acids, Nonesterified; 0/Hypoglycemic Agents; 0/Insulin; 0/Iodoacetates; 50-99-7/Glucose
Comments/Corrections

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