Glucose requirement for postischemic recovery of perfused working heart
Open Access
- 3 March 1990
- journal article
- research article
- Published by Wiley in European Journal of Biochemistry
- Vol. 188 (2), 481-493
- https://doi.org/10.1111/j.1432-1033.1990.tb15426.x
Abstract
The quantitative importance of glycolysis in cardiomyocyte reenergization and contractile recovery was examined in postischemic, preload-controlled, isolated working guinea pig hearts. A 25-min global but low-flow ischemia with concurrent norepinephrine infusion to exhaust cellular glycogen stores was followed by a 15-min reperfusion. With 5 mM pyruvate as sole reperfusion substrate, severe contractile failure developed despite normal sarcolemmal pyruvate transport rate and high intracellular pyruvate concentrations near 2 mM. Reperfusion dysfunction was characterized by a low cytosolic phosphorylation potential ([ATP]/([ADP][Pi]) due to accumulations of inorganic phosphate (Pi) and lactate. In contrast, with 5 mM glucose plus pyruvate as substrates, but not with glucose as sole substrate, reperfusion phosphorylation potential and function recovered to near normal. During the critical ischemia-reperfusion transition at 30 s reperfusion the cytosolic creatine kinase appeared displaced from equilibrium, regardless of the substrate supply. When under these conditions glucose and pyruvate were coinfused, glycolytic flux was near maximum, the glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase reaction was enhanced, accumulation of Pi was attenuated, ATP content was slightly increased, and adenosine release was low. Thus, glucose prevented deterioration of the phosphorylation potential to levels incompatible with reperfusion recovery. Immediate energetic support due to maximum glycolytic ATP production and enhancement of the glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase reaction appeared to act in concert to prevent detrimental collapse of [ATP]/([ADP][Pi]) during creatine kinase dysfunction in the ischemia-reperfusion transition. Dichloroacetate (2 mM) plus glucose stimulated glycolysis but failed fully to reenergize the reperfused heart; conversely, 10 mM 2-deoxyglucose plus pyruvate inhibited glycolysis and produced virtually instantaneous de-energization during reperfusion. The following conclusions were reached. (1) A functional glycolysis is required to prevent energetic and contractile collapse of the low-flow ischemic or reperfused heart (2). Glucose stabilization of energetics in pyruvate-perfused hearts is due in part to intensification of glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase activity. (3) 2-Deoxyglucose depletes the glyceraldehyde-3-phosphate pool and effects intracellular phosphate fixation in the form of 2-deoxyglucose 6-phosphate, but the cytosolic phosphorylation potential is not increased and reperfusion failure occurs instantly. (4) Consistent correlations exist between cytosolic ATP phosphorylation potential and reperfusion contractile function. The findings depict glycolysis as a highly adaptive emergency mechanism which can prevent deleterious myocyte deenergization during forced ischemia-reperfusion transitions in presence of excess oxidative substrate.This publication has 40 references indexed in Scilit:
- Pyruvate‐enhanced phosphorylation potential and inotropism in normoxic and postischemic isolated working heartEuropean Journal of Biochemistry, 1989
- Cytosolic adenylates and adenosine release in perfused working heartEuropean Journal of Biochemistry, 1986
- Pyruvate attenuation of hypoxia damage in isolated working guinea-pig heartJournal of Molecular and Cellular Cardiology, 1986
- The change of the free energy of ATP hydrolysis during global ischemia and anoxia in the rat heartIts possible role in the regulation of transsarcolemmal sodium and potassium gradientsJournal of Molecular and Cellular Cardiology, 1984
- On the inability of ketone bodies to serve as the only energy providing substrate for rat heart at physiological work loadBasic Research in Cardiology, 1983
- Mechanism of pyruvate dehydrogenase activation by increased cardiac workJournal of Molecular and Cellular Cardiology, 1983
- Novel dihydropyridines with positive inotropic action through activation of Ca2+ channelsNature, 1983
- Free energy change of ATP-hydrolysis: a causal factor of early hypoxic failure of the myocardium?,Journal of Molecular and Cellular Cardiology, 1982
- The Effect of Insulin and Growth Hormone on the Flux of Tracer from Labelled Lactate in Perfused Rat HeartEuropean Journal of Biochemistry, 1973
- Untersuchungen über die Substratspezifität der Glucose-6-phosphat-DehydrogenaseHoppe-Seyler´s Zeitschrift Für Physiologische Chemie, 1965