Skip to main content
SpringerLink
Log in

Der Kupfferzell-abhängige Reperfusionsschaden nach Lebertransplantation: Neuer klinisch relevanter Einsatz von Glycin

Kupffer Cell-dependent Reperfusion Injury in Liver Transplantation: New Clinically Relevant Use of Glycine

  • Conference paper
Vielfalt und Einheit der Chirurgie Humanität und Wissenschaft

Part of the book series: Langenbecks Archiv für Chirurgie ((KONGRESSBAND,volume 1998))

  • 16 Accesses

Summary

Kupffer cell-dependent reperfusion injury occurs to the liver following transplantation, most often in fatty livers which fail most frequently due to primary nonfunction. Failure was largely blocked with Carolina rinse solution, which contains glycine, and prevents the activation of Kupffer cells. Furthermore, gentle in situ organ manipulation, which cannot be prevented using standard harvesting techniques, has a detrimental effect on survival. These effects were also prevented by glycine. Since proteolytic activity is increased in both fatty and manipulated livers, amino acids were measured in rinse effluents collected at harvest. A combination of four amino acids correlated with graft function. It is concluded that glycine could be beneficial in clinical liver transplantation to prevent reperfusion injury, and that amino acids measured at harvest may predict graft function.

Zusammenfassung

Kupfferzellabhängiger Reperfusionsschaden führt vor allem bei Fettlebern häufig zum primären Transplantatversagen. Glycin, ein Bestandteil der Carolina Rinse Solution, blockt Kupfferzellaktivierung und verhindert primäres Transplantatversagen. Vorsichtige Manipulation der Leber in situ reduziert das Transplantatüberleben ähnlich einer Spenderoperation in Standardtechnik. Dies wird ebenfalls durch Glycin verhindert. Proteolyse ist sowohl in Fettlebern als auch nach Manipulation erhöht. Die Zusammensetzung von Aminosäuren im Effluat einer Spenderleber korreliert mit späterer Transplantatfunktion. Während Glycin primäres Transplantatversagen verhindert, können vier bestimmte Aminosäuren im Effluat die Transplantatfunktion vorhersagen.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 59.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 74.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Caldwell-Kenkel JC, Thurman RG, Lemasters JJ (1988) Selective loss of nonparenchymal cell viability after cold ischemic storage of rat livers. Transplantation 45: 834.

    Article  PubMed  CAS  Google Scholar 

  2. Bremer C, Bradford BU, Hunt KJ et al. (1994) Role of Kupffer cells in the pathogenesis of hepatic reperfusion injury. Am J Physiol 267: G 630.

    Google Scholar 

  3. Takei Y, Gao W, Hijioka T et al. (1991) Increase in survival of liver grafts after rinsing with warm Ringer’s solution due to improvement of hepatic microcirculation. Transplantation 52: 225.

    Article  PubMed  CAS  Google Scholar 

  4. Takei Y, Marzi I, Gao W, Gores GJ, Lemasters JJ, Thurman RG (1991) Leukocyte adhesion and cell death following orthotopic liver transplantation in the rat. Transplantation 51: 959.

    Article  PubMed  CAS  Google Scholar 

  5. Currin RT, Reinstein LJ, Lichtman SN, Thurman RG, Lemasters JJ (1993) Inhibition of tumor necrosis factor release from cultured rat hepatocytes by agents that reduce graft failure from storage injury. Transplant Proc 25: 1631.

    PubMed  CAS  Google Scholar 

  6. Marzi I, Knee J, Buhren V, Menger M, Trentz O (1992) Reduction by Superoxide dismutase of leukocyte-endothelial adherence after liver transplantation. Surgery 111: 90.

    PubMed  CAS  Google Scholar 

  7. Sanchez-Urdazpal L, Gores GJ, Lemasters JJ et al. (1993) Carolina Rinse solution decreases liver injury during clinical liver transplantation. Transplant Proc 25: 1574.

    PubMed  CAS  Google Scholar 

  8. Cywes R, Brendan J, Mullen M et al. (1993) Prediction of the outcome of transplantation in man by platelet adherence in donor liver allografts. Transplantation 56: 316.

    Article  PubMed  CAS  Google Scholar 

  9. Jaeschke H, Farhood A (1991) Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver. Am J Physiol 260: G 355.

    Google Scholar 

  10. Koo A, Komatsu H, Tao G, Inoue M, Guth PH, Kaplowitz N (1991) Contribution of no-reflow phenomenon to hepatic injury after ischemia-reperfusion: evidence for a role of Superoxide anion. Hepatology 15: 507.

    Article  Google Scholar 

  11. Peng X-X, Currin RT, Musshafen TL, Thurman RG, Lemasters JJ (1995) Lipopolysaccharide treatment of donor rats causes graft failure after orthotopic liver transplantation. In: Wisse E, Knook DL, Wake K (eds) Cells of the Hepatic Sinusoid. Leiden, The Netherlands, The Kupffer Cell Foundation 234.

    Google Scholar 

  12. van Goor H, Rosman C, Grond J, Kooi K, Wubbels GH, Bleichrodt RP (1994) Translocation of bacteria and endotoxin in organ donors. Arch Surg. 129: 1063.

    Article  PubMed  Google Scholar 

  13. Todo S, Demetris AJ, Makowka L et al. (1989) Primary nonfunction of hepatic allografts with preexisting fatty infiltration. Transplantation 47: 903.

    Article  PubMed  CAS  Google Scholar 

  14. Teramoto K, Bowers JL, Kruskal JB, Clouse ME (1993) Hepatic microcirculatory changes after reperfusion in fatty and normal liver transplantation in the rat. Transplantation 56: 1076.

    Article  PubMed  CAS  Google Scholar 

  15. Hayashi M, Tokunaga Y, Fujita T, Tanaka K, Yamaoka Y, Ozawa K (1993) The effects of cold preservation on steatotic graft viability in rat liver transplantation. Transplantation 56: 282.

    Article  PubMed  CAS  Google Scholar 

  16. Gao W, Connor HD, Lemasters JJ, Mason RP, Thurman RG (1995) Primary nonfunction of fatty livers produced by alcohol is associated with a new, antioxidant-insensitive free radical species. Transplantation 59: 674.

    Article  PubMed  CAS  Google Scholar 

  17. Zhong Z, Connor H, Mason RP et al. (1996) Destruction of Kupffer cells increases survival and reduces graft injury after transplantation of fatty livers from ethanol-treated rats. Liver Transplant Surg 2: 383.

    Article  CAS  Google Scholar 

  18. Zhong Z, Connor HD, Mason RP et al. (1995) Role of Kupffer cells in reperfusion injury in fat-loaded livers from ethanol-treated rats. J Pharmacol Exp Ther 27: 1512.

    Google Scholar 

  19. Currin RT, Toole JG, Thurman RG, Lemasters JJ (1990) Evidence that Carolina rinse solution protects sinusoidal endothelial cells against reperfusion injury after cold ischemic storage of rat liver. Transplantation 50: 1076.

    Article  PubMed  CAS  Google Scholar 

  20. Gao W, Takei Y, Marzi I et al. (1991) Carolina Rinse solution: A new strategy to increase survival time after orthotopic liver transplantation in the rat. Transplantation 52: 417.

    Article  PubMed  CAS  Google Scholar 

  21. Bachmann S, Caldwell-Kenkel JC, Oleksy I, Steffen R, Thurman RG, Lemasters JJ (1992) Warm Carolina Rinse solution prevents graft failure from storage injury after orthotopic rat liver transplantation with arterialization. Transpl Int 5: 108.

    Article  PubMed  CAS  Google Scholar 

  22. Gao W, Currin RT, Lemasters JJ, Connor HD, Mason RP, Thurman RG (1992) Reperfusion rather than storage injury predominates following long-term (48 hrs) cold storage of grafts in UW solution: Studies with Carolina Rinse in transplanted rat liver. Transpl Int 5: S329.

    PubMed  Google Scholar 

  23. Gao W, Hijioka T, Lindert KA, Caldwell-Kenkel JC, Lemasters JJ, Thurman RG (1991) Evidence that adenosine is a key component in Carolina Rinse responsible for reducing graft failure after orthotopic liver transplantation in the rat. Transplantation 52: 992.

    Article  PubMed  CAS  Google Scholar 

  24. Bachmann S, Caldwell-Kenkel JC, Currin RT et al. (1992) Protection by pentoxifylline against graft failure from storage injury after orthotopic rat liver transplantation with arterialization. Transpl Int 5: S345.

    Article  PubMed  Google Scholar 

  25. Bachmann S, Caldwell-Kenkel JC, Currin RT et al. (1993) Ultrastructural correlates of liver graft failure from storage injury: studies of graft protection by Carolina rinse solution and pentoxifylline. TransplantProc 25: 1620.

    CAS  Google Scholar 

  26. Weinberg JM, Davis JA, Abarzua M, Rajan T (1987) Cytoprotective effects of glycine and glutathione against hypoxic injury to renal tubules. J Clin Invest 80: 1446.

    Article  PubMed  CAS  Google Scholar 

  27. Marsh DC, Vreugdenhil PK, Mack VE, Beizer FO, Southard JH (1993) Glycine protects hepatocytes from injury caused by anoxia, cold ischemia and mitochondrial inhibitors, but not injury caused by calcium ionophores or oxidative stress. Hepatology 17: 91.

    Article  PubMed  CAS  Google Scholar 

  28. Bachmann S, Peng X-X, Currin RT, Thurman RG, Lemasters JJ (1995) Glycine in Carolina rinse solution reduces reperfusion injury, improves graft function, and increases graft survival after rat liver transplantation. Transplant Proc 27: 741.

    PubMed  CAS  Google Scholar 

  29. Schemmer P, Schoonhoven R, Swenberg JA, Bunzendahl H, Thurman RG (1998) Gentle in situ liver manipulation during organ harvest decreases survival after rat liver transplantation: Role of Kupffer cells. Transplantation 65(8): 1009.

    Article  Google Scholar 

  30. Schemmer P, Bunzendahl H, Thurmann RG (1998) Donor pretreatment with glycine improves survival after liver transplantation in rats. Langenbecks Arch Chir 383(S1): 589.

    Google Scholar 

  31. Frankenberg M v, Forman DT, Frey W, Bunzendahl H, Lemasters JJ, Thurman RG (1997) Amino acids in storage solution predict primary nonfunction in fatty liver grafts. Transplant Proc 29: 1131.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Lab. of Hepatobiology and Toxicology, University of North Carolina, Chapel Hill, NC, 27599-7365, USA

    R. G. Thurman, P. Schemmer, Z. Zhong & M. von Frankenberg

  2. Dept. of Cell Biology and Anatomy, University of North Carolina, Chapel Hill, NC, 27599-7365, USA

    J. J. Lemasters

  3. Dept. of Surgery CB#7365, University of North Carolina, Mary Ellen Jones Bldg., Chapel Hill, NC, 27599-7365, USA

    H. Bunzendahl

Authors
  1. R. G. Thurman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Schemmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Z. Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Bunzendahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. von Frankenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. J. Lemasters
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Deutschen Gesellschaft für Chirurgie, Steinhölzle 16, D-89197, Westerstetten-Vorderdenkental, Deutschland

    W. Hartel (Generalsekretär) (Generalsekretär)

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Thurman, R.G., Schemmer, P., Zhong, Z., Bunzendahl, H., von Frankenberg, M., Lemasters, J.J. (1998). Der Kupfferzell-abhängige Reperfusionsschaden nach Lebertransplantation: Neuer klinisch relevanter Einsatz von Glycin. In: Hartel, W. (eds) Vielfalt und Einheit der Chirurgie Humanität und Wissenschaft. Langenbecks Archiv für Chirurgie, vol 1998. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45774-6_39

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-45774-6_39

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-65144-4

  • Online ISBN: 978-3-642-45774-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation