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Studies on the pathogenesis of ischemic cell injury

XI. P/O ratio and acceptor control

  • Published:
Virchows Archiv B

Summary

Acceptor control index, P/O ratio and inner membrane permeability were examined in isolated mitochondria following periods of renal ischemia for 15, 30, 60, 120, and 240 min. It was noted that the P/O ratio remained unchanged until 1–2 h after the onset of ischemia. A similar change was noted in the contraction rate of isolated ischemic mitochondria after swelling in KCl and addition of ATP + Mg2+. Both changes are probably indications of a basic membrane alteration which correlates with the occurrence of irreversibility of cell injury. In contrast, the swelling rate in KCl and the acceptor control index are altered almost simultaneously with the onset of ischemia. Therefore, acceptor control index and the rate of swelling are affected prior to the point of irreversible cell injury. They are not, therefore, good as indicators of irreversible changes in the inner membrane of mitochondria leading to the “point-of-no-return.”

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References

  1. Ames, A. III, Wright, R.L., Kowada, M., Thurston, J.M., Majno, G.: Cerebral ischemia. II. The no-reflow phenomenon. Am. J. Pathol.52, 437–453 (1968)

    PubMed  Google Scholar 

  2. Atkinson, D.E.: The energy charge of the adenylate pool as regulatory parameter. Interaction with feed back modifiers. Biochem.7, 4030–4040 (1968)

    Article  CAS  Google Scholar 

  3. Boime, I., Smith, E.E., Hunter, Jr., F.E.: Stability of oxidative phosphorylation and structural changes of mitochondria in ischemic rat liver. Arch. Biochem. Biophys.128, 704–715 (1968)

    Article  PubMed  CAS  Google Scholar 

  4. Boime, I., Smith, E.E., Hunter, F.E.: The role of fatty acids in mitochondrial changes during liver ischemia. Arch. Biochem. Biophys.139, 425–443 (1970)

    Article  PubMed  CAS  Google Scholar 

  5. Braasch, W., Gudbjarnason, S., Puri, P.S., Ravens, K.G., Bing, R.J.: Early changes in energy metabolism in the myocardium following acute coronary artery occlusion in anesthetized dogs. Circ. Res.23, 429–438 (1968)

    PubMed  CAS  Google Scholar 

  6. Chance, B., Williams, G.R.: Respiratory enzymes in oxidative phosphorylation in the steady state. J. Biol. Chem.217, 409–427 (1955)

    PubMed  CAS  Google Scholar 

  7. Croker, B., Saladino, A., Trump, B.F.: Ion movements in cell injury: Relationship between energy metabolism and the pathogenesis of lethal injury in the toad bladder. Am. J. Pathol.59, 247–278 (1970)

    PubMed  CAS  Google Scholar 

  8. Collan, Y., McDowell, E.M., Trump, B.F.: Studies on the pathogenesis of ischemic cell injury. VI. Mitochondrial flocculent densities of ischemia. Lab. Invest. (in press)

  9. Cuppage, F.E., Neagoy, D.R., Tate, A.: Repair of the nephron following temporary occlusion of the renal pedicle. Lab. Invest.17, 660–674 (1967)

    PubMed  CAS  Google Scholar 

  10. Daniel, P.M., Prichard, M.M.L., Ward-McQuaid, J.N.: The renal circulation after temporary occlusion of the renal artery. Brit. J. Biol.26, 118–126 (1959)

    Google Scholar 

  11. Estabrook, R.W.: Mitochondrial respiratory control and the polarographic measurements of ADP:0 ratios. In: Methods in Enzymology, Vol. X. (Colowick, S.P., and Kaplan, N.O., Eds.), pp. 41–47. New York: Academic Press 1967

    Google Scholar 

  12. Gomori, G.: A modification of the colorimetric phosphorus determination for use with the photoelectric colometer. J. Lab. Clin. Med.27, 955–960 (1942)

    CAS  Google Scholar 

  13. Haeffner, E.W., Privitt, O.S.: Effect of unsaturation in fatty acid-induced swelling of rat liver mitochondria. Experientia29, 797–798 (1973)

    Article  PubMed  CAS  Google Scholar 

  14. Hems, D.A., Brosnan, J.: Effects of ischemia on content of metabolites in rat liver and kidney in vivo. Biochem. J.120, 105–111 (1970)

    PubMed  CAS  Google Scholar 

  15. Jennings, R.B.: Early phase of myocardial ischemic injury and infarction. Amer. J. Cardiol.24, 753–765 (1970)

    Article  Google Scholar 

  16. Jennings, R.B., Baum, J.H., Herdson, P.B.: Fine structural changes in myocardial ischemic injury. Arch. Pathol.79, 135–143 (1965)

    PubMed  CAS  Google Scholar 

  17. Jennings, R.B., Herdson, P.B., Sommers, H.M.: Structural and functional abnormalities in mitochondria isolated from ischemic dog myocardium. Lab. Invest.20, 548–557 (1969)

    PubMed  CAS  Google Scholar 

  18. Jennings, R.B., Sommers, H.M., Herdson, P.B., Kaltenbach, J.P.: Ischemic injury of myocardium. Ann. N.Y. Acad. Sci.156, 61–78 (1969)

    Article  PubMed  CAS  Google Scholar 

  19. Koletsky, S.: Effects of temporary interruption of renal circulation in rats. Arch. Pathol.58, 492–603 (1959)

    Google Scholar 

  20. Koletsky, S., Gustafson, G.E.: The effects of temporary cessation of renal blood flow in rats. J. Clin. Invest.26, 1072–1078 (1947)

    Article  PubMed  CAS  Google Scholar 

  21. Kubier, W., Spieckermann, P.G.: Regulation of glycolysis in the ischemic and the anoxic myocardium. J. Molec. Cell Cardiol.1, 351–377 (1970)

    Article  Google Scholar 

  22. Lehninger, A.L.: The Mitochondrion. New York: Benjamin 1965

    Google Scholar 

  23. Mergner, W.J., Smith, M.A., Trump, B.F.: Studies on the pathogenesis of ischemic cell injury. IV. Alteration of ionic permeability of mitochondria from ischemic rat kidney. Exp. Mol. Pathol.26, 1–12 (1977)

    Article  PubMed  Google Scholar 

  24. Moore, K.E., Brody, T.M.: Functional changes in mitochondria following in situ anoxia. Am. J. Physiol.191, 677–681 (1960)

    Google Scholar 

  25. Penttila, A., Trump, B.F.: Extracellular acidosis protects Ehrlich ascites tumor cells and rat renal cortex against anoxic injury. Science185, 277–278 (1974)

    Article  PubMed  CAS  Google Scholar 

  26. Reimer, K.A., Ganote, G.E., Jennings, R.B.: Alterations in renal cortex following ischemic injury. III. Ultrastructure of proximal tubules after ischemia and autolysis. Lab. Invest.26, 347–363 (1972)

    PubMed  CAS  Google Scholar 

  27. Reimer, K.A., Jennings, R.B.: Alterations in renal cortex after ischemia or autolysis. Lab. Invest.25, 176–184 (1974)

    Google Scholar 

  28. Reimer, K.A., Jennings, R.B.: Alterations in renal cortex following ischemic injury. II. PAH uptake, O2 consumption and water content in slices of cortex after ischemia or autolysis. Lab. Invest.25, 185–195 (1971)

    PubMed  CAS  Google Scholar 

  29. Schneider, W.C., Hogeboom, G.H.: Cytochemical studies of mammalian tissues: the isolation of cell components by differential centrifugation: A review. Cancer Res.11, 1–22 (1951)

    PubMed  CAS  Google Scholar 

  30. Sheehan, H.L., Davis, J.C.: Renal ischemia with failed reflow. J. Path. Bact.78, 105–120 (1959)

    Article  PubMed  CAS  Google Scholar 

  31. Shen, A.C., Jennings, R.B.: Myocardial calcium and magnesium in acute ischemic injury. Am. J. Pathol.67, 417–440 (1972a)

    PubMed  CAS  Google Scholar 

  32. Shen, A.C., Jennings, R.B.: Kinetics of calcium accumulation in acute myocardial ischemic injury. Am. J. Pathol.67, 441–452 (1972b)

    PubMed  CAS  Google Scholar 

  33. Summers, W.K., Jamison, R.L.: The no reflow phenomenon in renal ischemia. Lab. Invest.25, 635–643 (1971)

    PubMed  CAS  Google Scholar 

  34. Tedeschi, H., Harris, D.L.: Some observations on the photometric estimation of mitochondrial volume. Biochem. Biophys. Acta28, 392–402 (1958)

    Article  PubMed  CAS  Google Scholar 

  35. Tedeschi, H., Harris, D.L.: The osmotic behavior and permeability to nonelectrolytes of mitochondria. Arch. Biochem. Biophys.58, 52–67 (1955)

    Article  PubMed  CAS  Google Scholar 

  36. Trump, B.F., Bulger, R.E.: Studies of cellular injury in isolated flounder tubules. IV. Electron microscopic observations of changes during the phase of altered homeostasis in tubules treated with cyanide. Lab. Invest.18, 731–739 (1968)

    PubMed  CAS  Google Scholar 

  37. Trump, B.F., Croker, B.P., Mergner, W.J.: The role of energy metabolism, ion and water shifts in the pathogenesis of cell injury. In: Cell Membranes: Biological and Pathological Aspects (Richter, G.W., and Scarpelli, D.G., Eds.), pp. 84–128. Baltimore: Williams & Wilkins 1971

    Google Scholar 

  38. Trump, B.F., Ginn, F.L.: Studies of cellular injury in isolated flounder tubules. II. Cellular swelling in high potassium media. Lab. Invest.18, 341–351 (1968)

    PubMed  CAS  Google Scholar 

  39. Trump, B.F., Goldblatt, P.J., Stowell, R.E.: An electron microscopic study of early cytoplasmic alterations in hepatic parenchymal cells of mouse liver during necrosis in vitro (autolysis). Lab. Invest.11, 986–1915 (1962)

    PubMed  CAS  Google Scholar 

  40. Trump, B.F., Mergner, W.J.: Cell injury. In: The Inflammatory Process. Vol. I, Second edition. (Zwiefach, B.W., Grant, L., and McClusky, R.T., Eds.), pp. 115–257. London and New York: Academic Press 1974

    Google Scholar 

  41. Umbreit, W.W., Burris, R.H., Stauffer, J.F.: Manometric Techniques. 4th edition, Minneapolis: Burgess Publishing Co. 1964

    Google Scholar 

  42. Vogt, M., Farber, E.: On the molecular pathology of ischemic renal cell death. Am. J. Pathol.53, 1–26 (1968)

    PubMed  CAS  Google Scholar 

  43. Weed, R.I., La Celle, P., Merrill, W.: Metabolic dependence of red cell deformability. J. Clin. Invest.48, 795–809 (1969)

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, University of Maryland School of Medicine, 21201, Baltimore, Maryland, USA

    Wolfgang J. Mergner, Mary W. Smith & Benjamin F. Trump

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  1. Wolfgang J. Mergner
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  2. Mary W. Smith
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  3. Benjamin F. Trump
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This is contribution UM #154 of the Cellular Pathobiology Laboratory

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Mergner, W.J., Smith, M.W. & Trump, B.F. Studies on the pathogenesis of ischemic cell injury. Virchows Arch. B Cell Path. 26, 17–26 (1978). https://doi.org/10.1007/BF02889532

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  • DOI: https://doi.org/10.1007/BF02889532

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