Pyruvate Dehydrogenase Activity and Malonyl CoA Levels in Normal and Ischemic Swine Myocardium: Effects of Dichloroacetate

The pruposes of this study were to: (1) assess myocardial pyruvate dehydrogenase (PDH) activity and substrate exchange under well-perfused and eschemic conditions; (2) determine the metabolic effects of an intra-coronary infusion of the PDH activator, dichloroacetate (DCA); and (3) measure the effec...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 1996-05, Vol.28 (5), p.905-914
Main Authors: Stanley, William C., Hernandez, Lisa A., Spires, Doreen, Bringas, John, Wallace, Sonja, McCormack, James G.
Format: Article
Language:English
Subjects:
Animals
carbohydrate
cardiac
Dichloroacetic Acid - administration & dosage
fatty acids
Infusions, Intra-Arterial
ischemia
Male
Malonyl Coenzyme A - analysis
Malonyl Coenzyme A - metabolism
mitochondria
Myocardial Ischemia - enzymology
Pyruvate Dehydrogenase Complex - analysis
Pyruvate Dehydrogenase Complex - metabolism
Swine
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Summary:The pruposes of this study were to: (1) assess myocardial pyruvate dehydrogenase (PDH) activity and substrate exchange under well-perfused and eschemic conditions; (2) determine the metabolic effects of an intra-coronary infusion of the PDH activator, dichloroacetate (DCA); and (3) measure the effects of ischemia and DCA on malonyl CoA levels. Experiments were performed in anesthetised open-chest swine under non-ischemic conditions, followed by 40 min with a 60% reduction in left anterior descending coronary artery (LAD) blood flow. Myocardial needle biopsies for measurement of PDH activity were taken after an intracoronary infusion of either saline or DCA (1mM in LAD blood) under aerobic conditions, and after 37 min of ischemia. Pyruvate dehydrogenase activity was measured with and without maximal activation by swine PDH phosphatase. Malonyl CoA and acetyl CoA were measured after 40 min of LAD ischemia in myocardium from the ischemic DCA- or saline-treated LAD bed, and the non-ischemic untreated left circumflex coronary artery (CFX) perfusion bed. Net glucose, lactate and free fatty acid (FFA) uptakes were measured across the LAD perfusion bed throughout the study. Dichloroacetate treatment increased the amount of active dephosphorylated PDH to 88% of the total activity under aerobic conditions, compared to 55% with saline ( P
ISSN:0022-2828
1095-8584
DOI:10.1006/jmcc.1996.0085