Mitochondrial Function in Normal and Hypoxic States of the Myocardium
The relationships among isometric tension development, the oxidation-reduction states of pyridine nucleotides and cytochrome c, and the oxygenation state of myoglobin have been assessed using the arterially perfused rabbit interventricular septum under different conditions of contraction rate, perfusate [Ca2+] and pH, catecholamine stress, and hypoxia. Hypoxia was produced either by decreasing oxygen availability with maintained flow (high-flow hypoxia) or by decreasing the flow rate (ischemia). Under normoxic conditions, increased work caused a fall of the cytosolic adenine nucleotide phosphorylation potential, ΔG (ATP)c, an oxidation of the pyridine nucleotides, and a reduction of cytochrome c; the opposite occurred with decreased work. Thus, the redox potential span from NADH to cytochrome c, ΔG h , varied with the energy demand such that ΔG h and ΔG (ATP)c changed in the same direction. Under hypoxic conditions, all respiratory components became more reduced, and myoglobin was partially deoxygenated. The percentage change of developed tension under hypoxic conditions was approximately proportional to the percentage change of oxidized cytochrome c. When high-flow hypoxia and ischemia were compared at the same rates of oxygen delivery, the developed tension at any level of cytochrome c reduction was always lower with ischemia than with high-flow hypoxia. This difference was attributed to the low intracellular pH of ischemic tissue. Myoglobin deoxygenation was linearly related to cytochrome c reduction under all conditions of hypoxia, indicating steep oxygen gradients. The results support the concept of heterogeneous oxygenation of the tissue with mixed populations of aerobic and anaerobic mitochondria in the hypoxic state. In the full aerobic state, the control of mitochondrial respiration in situ appears similar to that of isolated mitochondria.
KeywordsOxygen Tension Pyridine Nucleotide Tension Development Contraction Rate Isometric Tension
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- 2.Berne, R. M., and Rubio, R. 1979. Coronary circulation. In: R. M. Berne, N. Sperelakis, and S. R. Geiger (eds.), Handbook of Physiology: The Cardiovascular System, Vol. 1, pp. 873–952. American Physiological Society, Bethesda.Google Scholar
- 4.Dutton, P. L., Leigh, J. S., and Scarpa, A. 1978. Frontiers of Biological Energetics, Vol. II, pp. 1341–1554. Academic Press, New York.Google Scholar
- 11.Hempel, F. G., Jöbsis, F. F., La Manna, J. C, Rosenthal, M. R., and Saltzman, H. A. 1977. Oxidation of ceregral cytochrome aa 3 by oxygen plus carbon dioxide at hyperbaric pressure. J. Appl. Physiol. 43:872–877.Google Scholar
- 23.Rich, T. L., and Williamson, J. R. 1982. Assessment of oxygen gradients in cells and perfused interventricular septum by optical techniques. Am. J. Physiol. (submitted).Google Scholar
- 29.Steenbergen, C, and Williamson, J. R. 1980. Heterogeneous coronary perfusion during myocardial hypoxia. In: M. Tajuddin, B. Bhatia, H. H. Siddiqui, and G. Rona (eds.), Advances in Myocardiology, Vol. 2, pp. 271–284. University Park Press, Baltimore.Google Scholar
- 35.Williamson, J. R., Safer, B., Rich, T., Schaffer, S., and Kobayashi, K. 1975. Effects of acidosis on myocardial contractility and metabolism. Acta Med. Scand. [Suppl.] 587:95–111.Google Scholar
- 39.Van der Meer, R., Akerboom, T. P. M., Groen, A. K., and Tager, J. M. 1978. Relationship between oxygen uptake of perfused rat liver cells and the cytosolic phosphorylation state calculated from indicator metabolites and a redetermined equilibrium constant. Eur. J. Biochem. 84:421–428.PubMedCrossRefGoogle Scholar