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Oxygen dependence of energy state and cardiac work in the perfused rat heart
1Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia 19104.
Abstract:
The relationship between oxygen concentrations in arteries, cytosol, and mitochondria and high energy phosphate metabolism was studied in perfused rat hearts subjected to low and high workloads during gradual hypoxia. PCr, ATP, and Pi were measured by 31P-NMR. Myoglobin oxygenation and cytochrome aa3 oxidation were measured by the optical method. When influent oxygen tension was decreased gradually, PCr, ATP, %MbO2, %Cytaa3, cardiac work and MvO2 decreased while Pi and Pi/PCr increased in Langendorff and working hearts. These changes occurred, however, at higher PaO2 values in working hearts. The decrease of %MbO2 and %Cytaa3 in Langendorff hearts was parallel where the ratio of %MbO2 / %Cytaa3 was 1:1. However, this ratio was more than 1:1 in working hearts. It had been demonstrated that oxygen gradients change with changing oxygen consumption. Metabolic and heart work changes occurred simultaneously and significant changes occurred at low levels of %MbO2 and %Cytaa3. Some differences were observed between Langendorff and working hearts. Oxidative phosphorylation is a good indicator of ATP synthesis during hypoxia and is regulated by the intracellular oxygen concentration as well as oxygen gradients.