High levels of fatty acids delay the recoveryof intracellular pH and cardiac efficiency inpost-ischemic hearts by inhibiting glucose oxidation
Que Liu, MD*,
John C. Docherty, PhD ,
John C. T. Rendell, PhD,
Alexander S. Clanachan, PhD* and
Gary D. Lopaschuk, PhD*,*
* Cardiovascular Research Group, University of Alberta, Edmonton, Canada
National Research Council, Institute for Biodiagnostics, Winnipeg, Canada
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Figure 1 Effects of palmitate on the recovery of cardiac work, cardiac efficiency and pHi of isolated working rat hearts reperfused after ischemia. Values are mean ± SEM of eight glucose-perfused hearts (open circles) and eight glucose+palmitate perfused hearts (closed circles). 31P-NMR measurement of pHi was performed as described in the Methods section. Isolated working hearts were subjected to 20 min of global no-flow ischemia, followed by 40 min of aerobic reperfusion. *Significant time-treatment interaction as determined by two-way analysis of variance with repeated measures on time. After application of the Huyhn-Feldt correction, p values for the time-treatment interactions for cardiac work, cardiac efficiency and pHi are 0.004, 0.007 and <0.0001, respectively.
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Figure 2 Effects of 1.2 mmol/l palmitate on cumulative rates of glycolysis, glucose oxidation and H+ production from glucose metabolism during reperfusion of ischemic hearts. Values are means ± SEM of eight glucose perfused hearts (open circles) and eight glucose+palmitate perfused hearts (closed circles). Hearts were subjected to 30 min of aerobic perfusion, 20 min of global no-flow ischemia and 40 min of aerobic reperfusion. Pre-ischemic values taken at 30 min of aerobic perfusion. Values were determined between 10 and 40 min of reperfusion *Significant time-treatment interaction as determined by two-way analysis of variance with repeated measures on time. After application of the Huyhn-Feldt correction, p values for the time-treatment interactions for glycolysis, glucose oxidation and proton production are 0.533, <0.0001 and <0.0001, respectively.
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Figure 3 Effects of dichloroacetate (DCA) on the recovery of cardiac work, cardiac efficiency and pHi of hearts reperfused after ischemia. Values are mean ± SEM of eight glucose+palmitate perfused hearts (closed circles) and eight glucose+palmitate + DCA perfused hearts (closed triangles). Isolated working hearts were subjected to 20 min of global no-flow ischemia and 40 min of aerobic reperfusion. DCA (3 mmol/l) was added immediately before reperfusion. *Significant time-treatment interaction as determined by two-way analysis of variance with repeated measures on time. After application of the Huyhn-Feldt correction, p-values for the time-treatment interaction for cardiac work, cardiac efficiency and pHi are 0.004, 0.008 and <0.0001, respectively.
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Figure 4 Effects of dichloroacetate (DCA) on cumulative glycolysis, glucose oxidation and H+ production from glucose metabolism during reperfusion of ischemic hearts in the presence of 1.2 mmol/l palmitate. Values are means ± SEM of eight glucose+palmitate perfused hearts (closed circles) and eight glucose+palmitate+DCA perfused hearts (closed triangles). Hearts were subjected to 30 min of aerobic perfusion, 20 min of global no-flow ischemia and 40 min of aerobic reperfusion. Pre-ischemic values were taken at 30 min of aerobic perfusion. Values were determined between 10 and 40 min of reperfusion. Dichloroacetate (3 mmol/l), when present, was added immediately before reperfusion. *Significant time-treatment interaction as determined by two-way analysis of variance with repeated measures on time. After application of the Huyhn-Feldt correction, p values for the time-treatment interactions for glycolysis, glucose oxidation and proton production are 0.345, <0.0001 and 0.029, respectively.
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