Mitochondria in the Cold

  • Erich Gnaiger
  • Andrej V. Kuznetsov
  • Stefan Schneeberger
  • RÜdiger Seiler
  • Gerald Brandacher
  • Wolfgang Steurer
  • Raimund Margreiter
Conference paper

Abstract

Development of hibernation strategies for cold preservation of human organs represents a far-reaching goal in transplantation surgery. Short cold storage times of <6 h tolerated by the human heart remain a major clinical problem. Mitochondrial cold storagereperfusion injury is becoming recognized as a limiting factor in preservation of organs from non-hibernating mammals. Damaged mitochondria lead to cellular injury by reduction of ATP supply, oxidative stress, disturbance of ion balance, cytochrome c release and induction of apoptosis and necrosis. Profiles of mitochondrial injuries differed after (1) cold preservation of isolated rat heart mitochondria, (2) cold preservation of the rat heart, and (3) after transplantation and rewarming/reperfusion. Importantly, a specific defect of complex I of the electron transport chain, uncoupling of oxidative phosphorylation and the pronounced release of cytochromec from mitochondria were absent after cold storage but developed during reperfusion, in proportion to the loss of heart function. Cold preservation of isolated heart mitochondria could be significantly prolonged by a mitochondrial preservation solution containing antioxidants, mitochondrial substrates, ATP, histidine, and oncotic agents. Successful cold storage of heart mitochondria demonstrates a large scope for improvement of heart preservation solutions. In this context, comparison of intracellular conditions and cold ischemia-reperfusion injury in hibernating and non-hibernating mammals may provide a rationale for improvement of clinical organ hibernation strategies.

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References

  1. Bolling SF, Su T-P, Childs KF, Ning X-H, Horton N, Kilgore K, Oeltgen PR (1997) The use of hibernation induction triggers for cardiac transplant preservation. Transplantation 63: 326–329PubMedCrossRefGoogle Scholar
  2. Brustovetsky NN, Amerkhanov ZG, Popova Eyu, Konstantinov AA (1990) Reversible inhibition of electron transfer in the ubiquinol cytochrome c reductase segment of the mitochondrial respiratory chain in hibernating ground squirrels. FEBS Lett 263: 73–76PubMedCrossRefGoogle Scholar
  3. Brustovetsky NN, Egorova MV, Gnutov Dyu, Mokhova EN, Skulachev VP (1993) Cyclosporin A suppression of uncoupling in liver mitochondria of ground squirrel during arousal from hibernation. FEBS Lett 315: 233–236PubMedCrossRefGoogle Scholar
  4. Di Lisa F, Menabò R, Canton M, Petronilli V (1995) The role of mitochondria in the salvage and the injury of the ischemic myocardium. Biochim Biophys Acta 1366: 69–78Google Scholar
  5. Fedotcheva NJ, Sharyshev AA, Mironova GD, Kondrashova MN (1985) Inhibition of succinate oxidation and K+ transport in mitochondria during hibernation. Comp Biochem Physiol B 82: 191–195PubMedGoogle Scholar
  6. Garlid KD, Paucek P, Yarov-Yarovoy V, Murray HN, Darbenzio RB, D’Alonzo AJ, Lodge NJ, Smith MA, Grover GJ (1997) Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive KC channels. Possible mechanism of cardioprotection. Circ Res 81: 1072–1082PubMedCrossRefGoogle Scholar
  7. Ghafourifar P, Klein SD, Schucht O, Schenk U, Pruschy M, Rocha S, Richter C (1999) Ceramide induces cytochrome c release from isolated mitochondria. Importance of mitochondrial redox state. J Biol Chem 274: 6080–6084PubMedCrossRefGoogle Scholar
  8. Gnaiger E, Lassnig B, Kuznetsov AV, Rieger G, Margreiter R (1998) Mitochondrial oxygen affinity, respiratory flux control and excess capacity of cytochrome c oxidase. J exp Biol 201: 1129–1139PubMedGoogle Scholar
  9. Gnaiger E, Rieger G, Stadlmann S, Amberger A, Eberl T, Margreiter R (1999) Mitochondrial defect in endothelial cold ischemia/reperfusion injury. Transplant Proc 31: 994–995PubMedCrossRefGoogle Scholar
  10. Gnaiger E, Steinlechner-Maran R, Méndez G, Eberl T, Margreiter R (1995) Control of mitochondrial and cellular respiration by oxygen. J Bioenerg Biomembr 27: 583–596PubMedCrossRefGoogle Scholar
  11. Heldmaier G, Klingenspor M, Werneyer M, Lampi BJ, Brooks SP, Storey B (1999) Metabolic adjustments during daily torpor in the Djungarian hamster. Am J Physiol 276: E896-E906PubMedGoogle Scholar
  12. Heldrnaier G, Ruf T(1992) Body temperature and metabolic rate during natural hypothermia in endotherms. J Comp Physiol B 162: 696–706CrossRefGoogle Scholar
  13. Hochachka PW, Guppy M(1987) Metabolic arrest and the control of biological time. Harvard University Press, Cambridge, Mass.Google Scholar
  14. Kay L, Daneshrad Z, Saks VA, Rossi A (1997) Alteration in the control of mitochondrial respiration by outer mitochondrial membrane and creatine during heart preservation. Cardiovasc Res 34: 547–556PubMedCrossRefGoogle Scholar
  15. Ku K, Oku H, Alam MS, Saitoh Y, Nosaka S, Nakayama K (1997) Prolonged hypothermic cardiac storage with histidine-tryptophan-ketoglutarate solution. Transplantation 64: 971–975PubMedCrossRefGoogle Scholar
  16. Kuznetsov AV, Brandacher G, Steurer W, Margreiter R, Gnaiger E (1999) Estimation of mitochondrial damage in heart preservation. Transplant Proc 31: 992PubMedCrossRefGoogle Scholar
  17. Kuznetsov AV, Brandacher G, Steurer W, Margreiter R, Gnaiger E (2000) Isolated rat heart mitochondria and whole rat heart as models for mitochondrial cold ischemia-reperfusion injury. Transplant Proc 32 (in press)Google Scholar
  18. Lemasters JJ, Bond JM, Currin RT, Nieminen A-L, Caldwell-Kenkel JC, Harrison DC, Kaplan SH, Cascio WE, Thurman RG, Gores GJ, Herman B (1993) Reperfusion injury to heart and liver cells: Protection by acidosis during ischemia and a “pH paradox” after reperfusion. In: Hochachka PW, Lutz PL, Sick T, Rosenthal M, Van den Thillart G (eds.) Surviving hypoxia: Mechanisms of control and adaptation. CRC Press, Boca Raton Ann Arbor London Tokyo, pp 495–507Google Scholar
  19. Martin SL, Maniero GD, Carey C, Hand SC (1999) Reversible depression of oxygen consumption in isolated liver mitochondria during hibernation. Physiol Biochem Zool 72: 255–264PubMedCrossRefGoogle Scholar
  20. Menasché P, Pradier F, Grousset C, Peynet J, Mouas C, Bloch G, Piwnica A (1993) Improved recovery of heart transplants with a specific kit of preservation solutions. J Thorac Cardiovasc Surg 105: 353–363PubMedGoogle Scholar
  21. Opie LH (1997) The heart. Physiology, from cell to circulation. Lippincott-Raven, Philadelphia New YorkGoogle Scholar
  22. Parce JW, Spach PI, Cunningham CC (1980) Deterioration of rat liver mitochondria under conditions of metabolite deprivation. Biochem J 188: 817–822PubMedGoogle Scholar
  23. Saks VA, Veksler VI, Kuznetsov AV, Kay L, Sikk P, Tiivel T, Tranqui L, Olivares J, Winkler K, Wiedemann F, Kunz WS (1998) Permeabilized cell and skinned fiber techniques in studies of mitochondrial function in vivo. Mol Cell Biochem 184: 81–100PubMedCrossRefGoogle Scholar
  24. Scholte HR, Yu Y, Ross JD, Oosterkamp II, Boonman AM, Busch HF (1997) Rapid isolation of muscle and heart mitochondria, the lability of oxidative phosphorylation and attempts to stabilize the process in vitro by taurine, carnitine and other compounds. Mol Cell Biochem 174: 61–66PubMedCrossRefGoogle Scholar
  25. Southard JH, Belzer FO (1995) Organ preservation. Annu Rev Med 46: 235–247PubMedCrossRefGoogle Scholar
  26. Steinlechner-Maran R, Eberl T, Kunc M, Schröcksnadel H, Margreiter R, Gnaiger E (1997) Respiratory defect as an early event in preservation/reoxygenation injury in endothelial cells. Transplantation 63: 136–142PubMedCrossRefGoogle Scholar
  27. Storey KB (1997) Metabolic regulation in mammalian hibernation: enzyme and protein adaptations. Comp Biochem Physiol A 118: 1115–1124CrossRefGoogle Scholar
  28. Sumeray MS, Yellon DM (1999) Ischemic preconditioning. In: Grace PA, Mathie RT (eds) Ischemia-reperfusion injury.Blackwell Science, Oxford, pp 328–343Google Scholar
  29. Tseng EE, Cameron DE (1999) Myocardial protection from ischemia-reperfusion injury in cardiac surgery. In: Grace PA, Mathie RT (eds) Ischemia-reperfusion injury.Blackwell Science, Oxford, pp 344–356Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Erich Gnaiger
    • 1
  • Andrej V. Kuznetsov
    • 1
  • Stefan Schneeberger
    • 1
  • RÜdiger Seiler
    • 1
  • Gerald Brandacher
    • 1
  • Wolfgang Steurer
    • 1
  • Raimund Margreiter
    • 1
  1. 1.Department of Transplant Surgery, D. Swarovski Research LaboratoryUniversity Hospital InnsbruckInnsbruckAustria

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