Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia.

Lopaschuk, Gary D.; Spafford, Marguerite A.; Davies, Norman J.; Wall, Stephen R.

doi:10.1161/01.res.66.2.546

Cited by 220 publications

(129 citation statements)

References 35 publications

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“…Moreover, pharmacological inhibition of fatty acid oxidation (ie, inhibition of carnitine palmitoyltransferase I) has also been shown to be beneficial to the reperfused ischemic heart. 33 Thus, our data with regard to FAT/CD36-KO hearts are more consistent with previously published data than the results of Irie et al 21 One observation made in the study of Irie et al 21 that cannot be attributed to perfusion conditions is that nonperfused FAT/CD36-KO hearts exhibited lower levels of ATP than the wild-type hearts. This decrease in ATP may reflect lower energy production in vivo due to decreased rates of fatty acid oxidation.…”

Section: Discussionsupporting

confidence: 92%

Fatty Acid Translocase/CD36 Deficiency Does Not Energetically or Functionally Compromise Hearts Before or After Ischemia

et al. 2004

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Background-Evidence from humans suggests that fatty acid translocase (FAT)/CD36 deficiency can lead to functionally and/or energetically compromised hearts, but the data are equivocal, and the subject remains controversial. In this report we assessed the contribution of FAT/CD36 to overall fatty acid oxidation rates in the intact heart and determined the effect of FAT/CD36 on energy metabolism during reperfusion of ischemic hearts. Methods and Results-Isolated working hearts from wild-type and FAT/CD36-knockout (KO) mice were perfused with Krebs-Henseleit solution containing 0..5 mmol/L calcium, and 100 U/mL insulin at a preload pressure of 11.5 mm Hg and afterload pressure of 50 mm Hg. Hearts were aerobically perfused for 30 minutes or aerobically perfused for 30 minutes, followed by 18 minutes of global no-flow ischemia and 40 minutes of aerobic reperfusion. Rates of fatty acid oxidation in FAT/CD36-KO hearts were significantly lower than in wild-type hearts at both concentrations of palmitate (0.4 or 1.2 mmol/L). In addition, hearts from FAT/CD36-KO mice displayed a compensatory increase in glucose oxidation rates. On aerobic reperfusion after ischemia, cardiac work of FAT/CD36-KO hearts recovered to the same extent as wild-type hearts. Conclusions-FAT/CD36-deficient

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Section: Discussionsupporting

confidence: 92%

Fatty Acid Translocase/CD36 Deficiency Does Not Energetically or Functionally Compromise Hearts Before or After Ischemia

et al. 2004

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“…Aside from oxaloacetate (OAA), pyruvate also supplies acetyl-CoA to the CAC. Both pyruvate carboxylation and decarboxylation were linked to some beneficial effects on heart function (16,(23)(24)(25)(26)(27), although the partitioning of pyruvate through these two reactions remains to be clarified. Using 14 C-and 13 C-labeled substrates, several authors documented the reciprocal regulation of pyruvate decarboxylation and fatty acid oxidation (see for example Refs.…”

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confidence: 99%

A 13C Mass Isotopomer Study of Anaplerotic Pyruvate Carboxylation in Perfused Rat Hearts

Comte

Vincent

Bouchard

et al. 1997

Journal of Biological Chemistry

113

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Anaplerotic pyruvate carboxylation was examined in hearts perfused with physiological concentrations of glucose, [U-13 C 3 ]lactate, and [U-13 C 3 ]pyruvate. Also, a fatty acid, [1-13 C]octanoate, or ketone bodies were added at concentrations providing acetyl-CoA at a rate resulting in either low or substantial pyruvate decarboxylation. Relative contributions of pyruvate and fatty acids to citrate synthesis were determined from the 13 C labeling pattern of effluent citrate by gas chromatography-mass spectrometry (see companion article, Comte, B., Vincent, G., Bouchard, B., and Des Rosiers, C. (1997) J. Biol. Chem. 272, 26117-26124). Precision on flux measurements of anaplerotic pyruvate carboxylation depended on the mix of substrates supplied to the heart. Anaplerotic fluxes were precisely determined under conditions where acetyl-CoA was predominantly supplied by ␤-oxidation, as it occurred with 0.2 or 1 mM octanoate. Then, anaplerotic pyruvate carboxylation provided 3-8% of the OAA moiety of citrate and was modulated by concentrations of lactate and pyruvate in the physiological range. Also, the contribution of pyruvate to citrate formation through carboxylation was equal to or greater than through decarboxylation. Furthermore, 13 C labeling data on tissue citric acid cycle intermediates and pyruvate suggest that (i) anaplerosis occurs also at succinate and (ii) cataplerotic malate decarboxylation is low. Rather, the presence of citrate in the effluent perfusate of hearts perfused with physiological concentrations of glucose, lactate, and pyruvate and concentrations of octanoate leading to maximal oxidative rates suggests a cataplerotic citrate efflux from mitochondria to cytosol. Taken altogether, our data raise the possibility of a link between pyruvate carboxylation and mitochondrial citrate efflux. In view of the proposed feedback regulation of glycolysis by cytosolic citrate, such a link would support a role of anaplerosis and cataplerosis in metabolic signal transmission between mitochondria and cytosol in the normoxic heart.

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“…Increased glucose metabolism has been demonstrated in reperfused relative to normal myocardium 24 hours after reperfusionl-4; however, early after reperfusion (0-3 hours), no such increase is observed. [4][5][6][7] The increase in glucose ; by an investigative group uptake in reperfused myocardium 24 hours after reperfusion reflects at least in part enhanced nonoxidative glucose utilization. 3 Qualitative evaluation of glucose utilization in chronically instrumented dogs demonstrated that glucose metabolism remained significantly higher in postischemic myocardium relative to remote normal myocardium 1 week after reperfusion.2 Quantitative measurements in chronically instrumented dogs demonstrated that relative enhancement of glucose metabolism in postischemic myo-cardium was observed only when glucose metabolism in normal myocardium was low.…”

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confidence: 99%

Quantitative assessment of prolonged metabolic abnormalities in reperfused canine myocardium.

et al. 1992

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Background. Prolonged metabolic abnormalities have been demonstrated previously in postischemic myocardium, including relative increases in glucose uptake and abnormal fatty acid kinetics. However, quantitative metabolic information is limited, and the time course of changes in MVo2 in postischemic myocardium is unknown. To address these issues, chronically instrumented dogs were studied serially over 1 month after transient left anterior descending coronary artery (LAD) occlusion, using positron emission tomography.Methods and Results. Dynamic imaging protocols were used in conjunction with tracer kinetic models to quantify blood flow and metabolic rates. Myocardial sectors were defined as normal, predominantly reversibly injured, and infarct-containing, based on occlusion blood flow images and postmortem histochemistry. Myocardial blood flow and metabolism were homogeneous at baseline. During LAD occlusion for 3 hours, myocardial blood flow in reversibly injured and infarct-containing sectors (determined with 13NH3) was decreased to 46% and 23%, respectively, of blood flow in normal tissue.

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Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia.

Cited by 220 publications

References 35 publications

Fatty Acid Translocase/CD36 Deficiency Does Not Energetically or Functionally Compromise Hearts Before or After Ischemia

Fatty Acid Translocase/CD36 Deficiency Does Not Energetically or Functionally Compromise Hearts Before or After Ischemia

A 13C Mass Isotopomer Study of Anaplerotic Pyruvate Carboxylation in Perfused Rat Hearts

Quantitative assessment of prolonged metabolic abnormalities in reperfused canine myocardium.

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