The effect of intracellular oxygen concentration on lactate release, pyridine nucleotide reduction, and respiration rate in the rat cardiac tissue.
By measuring the absorbance change due to myoglobin oxygenation in hemoglobin-free isolated perfused rat hearts, we analyzed effects of perfusion pressure and heart rate upon the intracellular oxygen concentration. With Langendorff perfusion, the cardiac tissue was kept normoxic (above 50 microM O2) at aortic pressure above 50 cm H2O, but became hypoxic (8 microM O2) at 30 cm H2O. The increase in cardiac work, expressed as the product of peak systolic pressure and heart rate, increased oxygen consumption at aortic pressure of 50-200 cm H2O. The heart was kept normoxic under these conditions. Lactate release, oxygen consumption, and the oxidation-reduction state of pyridine nucleotide were measured as a function of myoglobin oxygenation under various normoxic and anoxic conditions. Pyridine nucleotide fluorescence and lactate release started to increase as the intracellular oxygen concentration decreased to 6 and 10 microM, respectively. Oxygen consumption was kept constant until the oxygen concentration decreased to 10 microM and slowed down below it. A close relationship between oxygen consumption and lactate release was observed. Infusions of epinephrine and norepinephrine under normoxic perfusion conditions increased cardiac work, oxygen consumption, and lactate release. More than 50% of myoglobin was then deoxygenated even under normoxic perfusion conditions. The increase in lactate release was ascribable to the increase in glycolytic flux caused by hypoxia. The change of pyridine nucleotide fluorescence by epinephrine was also explained by hypoxia in cardiac tissue.
D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006019:Glycolysis; D006339:Heart Rate; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000502:physiology*; D010101:Oxygen Consumption; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D007773:Lactates; D009211:Myoglobin; D009243:NAD; D019344:Lactic Acid; D010100:Oxygen; D004298:Dopamine; D004837:Epinephrine