Skip to main content
SpringerLink
Log in

Intravital studies on beneficial effects of warm Ringer's lactate rinse in liver transplantation

  • Original Article
  • Published:
Transplant International

Abstract

This quantitative in vivo fluorescence microscopy study investigated the impact of warm versus cold Ringer's lactate (RL) graft rinse on various microvascular manifestations of ischemia-reperfusion injury after liver translantation in the rat. Syngeneic orthotopic liver transplantation, including arterial revascularization, was performed in male Lewis rats following 24 h of cold storage in University of Wisconsin (UW) solution. In one group (n=8) liver grafts were rinsed with 4°C (cold) RL, whereas in the other group (n=8) grafts were rinsed with 37°C (warm) RL immediately prior to revascularization. Hepatic microvascular perfusion, leukocyteendothelium interaction, and Kupffer cell activation were quantified 30–90 min after graft reperfusion by direct visualization with intravital fluorescence microscopy. Moreover, biliary excretory graft function was analyzed by determination of bile flow and bile salt excretion during the first 90 min after reperfusion. Compared to grafts rinsed with cold RL, acinar and sinusoidal perfusion were found to be significantly increased after rinsing the grafts with warm RL. The amount of nonperfused acini declined from 18.1%±4.0% to 7.4%±1.6% (P<0.05), and the total percentage of perfused sinusoids increased from 80.1±1.4 to 88.4±1.2 (P<0.001) after cold and warm rinse, respectively. After rinsing the graft with warm RL, WBC adherence in sinusoids and especially in postsinusoidal venules decreased significantly by 28% (P<0.001) and 33% (P<0.001), respectively. Kupffer cell activation was markedly reduced after rinsing with RL at 37°C, as indicated by a decelerated adherence of latex particles injected 80 min after reperfusion. Excretory graft function was dramatically increased following warm RL rinse during the 90-min observation period. Bile flow was enhanced from 1.04±0.5 to 3.9±0.8 ml/100 g liver per 90 min (P<0.01), with a parallel rise in bile salt excretion from 24.3±5.8 to 128.0±19.8 mmol/100 g liver per 90 min (P<0.05) when compared to cold RL. These data strongly suggest that rinsing liver grafts with warm RL prior to reperfusion represents a simple and inexpensive way to reduce the incidence of primary graft failure secondary to ischemia and reperfusion injury in liver transplantation.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Adem CG, Harness JB (1981) Computer control of a modified Langendorff perfusion apparatus for organ preservation using cryoprotective agents. J Biomed Eng 3:134–139

    Google Scholar 

  2. Bachmann S, Caldwell-Kenkel JC, Olesky 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 5:108–114

    Google Scholar 

  3. Belzer FO, Southard JH (1988) Principles of solid-organ presenrvation by cold-storage. Transplantation 45:673–676

    Google Scholar 

  4. Blide T (1976) Vascular resistance in hypothermically perfused kidneys damaged by warm ischemia. Scand J Urol Nephrol 10:43–48

    Google Scholar 

  5. Bowers BA, Branum GD, Rotolo FS, Watters CR, Meyers WC (1987) Bile flow — an index of ischemic injury. J Surg Res 42:565–569

    Google Scholar 

  6. Butcher EC (1991) Leukocyte-endothelial cell recognition: three (or more) steps to specifity and diversity. Cell 67: 1033–1036

    Google Scholar 

  7. Caldwell-Kenkel JC, Currin RT, Tanaka Y, Thurman RG, Lemasters JJ (1991) Kupffer cell activation and endothelial cell damage after storage of rat livers: effects of reperfusion. Hepatology 13: 83–95

    Google Scholar 

  8. Clavien PA, Harvey PRC, Strasberg SM (1992) Preservation and reperfusion injuries in liver allografts. Transplantation 53:957–978

    Google Scholar 

  9. Connor HD, Gao W, Sadayuki N, Lemasters JJ, Mason RP, Thurman RG (1992) Evidence that free radicals are involved in graft failure following orthotopic liver transplantation in the rat — an electron paramagnetic resonance spin trapping study. Transplantation 54: 199–204

    Google Scholar 

  10. Emre S, Schwartz ME, Mor E, Kishakawa K, Yagmur O, Thiese N, Sheiner P, Jindal RM, Chiodini S, Miller CM (1994) Obviation of prereperfusion rinsing and decrease in preservation/reperfusion injury in liver transplantation by portal blood flushing. Transplantation 57:799–803

    Google Scholar 

  11. Furuyashiki S, Sumimoto K, Oku J, Kimura A, Fukuda Y, Dohi K, Kawasaki T (1994) The significance of bile secretion after the transplantation of long-preserved livers in the rat. Surg Today 24:59–62

    Google Scholar 

  12. Jaeschke H, Farhood A (1991) Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver. Am J Physiol 260:G355-G362

    Google Scholar 

  13. Jaeschke H, Farhood A, Smith CW (1990) Neutrophils contribute to ischemia/reperfusion injury in rat liver in vivo. FASEB J 4:3355–3359

    Google Scholar 

  14. Jamieson NV, Sundberg R, Lindell S, Southard JH, Belzer FO (1988) A comparison of cold storage solutions for hepatic preservation using the isolated perfused rabbit liver. Cryobiology 25: 300–310

    Google Scholar 

  15. Kamada N, Calne RY (1983) A surgical experience with five hundred thirty liver transplants in the rat. Surgery 93: 64–69

    Google Scholar 

  16. Konno H, Hardison WG, Miyai K (1991) Reoxygenation injury following anoxic perfusion preferentially impairs bile-acid-independent bile flow. Eur Surg Res 23:151–157

    Google Scholar 

  17. Malik KU (1969) Effect of temperature changes on the tone of perfused mesenteric arteries of rat and on the perfusion pressure responses to sympathetic nerve stimulation and injected noradremaline. J Pharm Pharmacol 21:472–473

    Google Scholar 

  18. Marzi I, Cowper K, Takei Y, Lindert K, Lemasters JJ, Thurman RG (1991) Methyl palmitate prevents Kupffer cell activation and improves survival after orthotopic liver transplantation in the rat. Transpl Int 4:215–220

    Google Scholar 

  19. Marzi I, Walcher F, Menger M, Bühren V, Harbauer G, Trentz O (1991) Microcirculatory disturbances and leucocyte adherence in transplanted livers after cold storage in EuroCollins, UW, and HTK solutions. Transpl Int 4:45–50

    Google Scholar 

  20. McKeown CMB, Edwards V, Phillips MJ, Harvey PRC, Petrunka CN, Strasberg SM (1988) Sinusoidal lining cell damage: the critical injury in cold preservation of liver allografts in the rat. Transplantation 46:178–191

    Google Scholar 

  21. Menegaux F, Egawa H, Keeffe EB, So SB, Concepcion W, Collins GM, Esquivel CO (1993) Comparative effects of blood, colloid, and Ringer's Lactate terminal allograft rinse on the results of orthotopic liver transplantation. Transplant Proc 25:3196–3198

    Google Scholar 

  22. Menger MD, Pelikan S, Steiner D, Messmer K (1992) Microvascular ischemia-reperfusion injury in striated muscle: significance of “reflow paradox”. Am J Physiol 263:H1892-H1900

    Google Scholar 

  23. Okouchi Y, Sasaki K, Tamaki T (1994) Ultrastructural changes in hepatocytes, sinusoidal endothelial cells and macrophages in hypothermic preservation of the rat liver with University of Wisconsin solution. Virchows Arch 424:477–484

    Google Scholar 

  24. Post S, Goerig M, Otto G, Manner M, Senninger N, Kommerell B, Herfarth C (1990) Prostanoid release in experimental liver transplantation. Translantation 49:490–494

    Google Scholar 

  25. Post S, Gonzalez AP, Palma P, Rentsch M, Menger MD (1992) Assessment of hepatic phagocytic activity by in vivo microscopy after liver transplantation in the rat. Hepatology 16:803–809

    Google Scholar 

  26. Post S, Menger MD, Rentsch M, Gonzalez AP, Herfarth C, Messmer K (1992) Impact of arterialization on hepatic microcirculation and leukocyte accumulation after liver transplantation in the rat. Transplantation 54:789–794

    Google Scholar 

  27. Post S, Palma P, Rentsch M, Gonzalez AP, Menger MD (1993) Differential impact of Carolina Rinse and University of Wisconsin solution on microcirculation, leukocyte adhesion, Kupffer cell activity, and biliary excretion after liver transplantation. Hepatology 18: 1490–1497

    Google Scholar 

  28. Post S, Palma P, Gonzalez AP, Rentsch M, Menger MD (1994) Timing of arterialization in liver transplantation. Ann Surg 220:691–698

    Google Scholar 

  29. Rao PN, Liu T, Synder JT, Platt JL, Starzl TE (1991) Reperfusion injury following cold ischemia activates rat liver Kupffer cells. Transplant Proc 23: 666–669

    Google Scholar 

  30. Sankary HN, Foster P, Brown E, Hart M, Williams JW (1991) A comparison of Collins and UW solutions for cold ischemic preservation of the rat liver. J Surg Res 51:87–91

    Google Scholar 

  31. Schachter D (1984) Fluidity and function of hepatocyte plasma membrane. Hepatology 4:140–151

    Google Scholar 

  32. Schmid-Schönbein GW, Fung YC, Zweifach BW (1975) Vascular endothelium-leukocyte interaction. Sticking shear force in venules. Circ Res 36:173–184

    Google Scholar 

  33. Steffen R, Ferguson DM, Krom RAF (1989) A new method for orthotopic rat liver transplantation with arterial cuff anastomosis to the recipient common hepatic artery. Transplantation 48:166–168

    Google Scholar 

  34. Steinhoff G, Behrend M, Schrader B, Duijvestijn AM, Wonigeit K (1993) Expression patterns of leukocyte adhesion ligand moleculas on human liver endothelia. Lack of ELAM-1 and CD62 inducibility on sinusoidal endothelia and distinct distribution of VCAM-1, ICAM-1, I. Am J Physiol 142:481–488

    Google Scholar 

  35. Takei Y, Gao WS, Hijioka T, Savier E, Lindert KA, Lemasters JJ, Thurman RG (1991) Increase in survival of liver grafts after rinsing with warm Ringer's solution due to improvement of hepatic microcirculation. Transplantation 52: 225–230

    Google Scholar 

  36. Talalay P (1960) Enzymatic analysis of steroid hormones. Methods Biochem Anal 8:119–128

    Google Scholar 

  37. Thurman RG, Bunzendahl H, Lemasters JJ (1993) Role of sinusoidal lining cells in hepatic reperfusion injury following cold storage and translantation. Semin Liver Dis 13:93–100

    Google Scholar 

  38. Von Andrian UH, Hansell P, Chambers JD, Berger EC, Filho Ivo Torres, Butcher EC, Arfors KE (1992)_L-selectin function is required for beta 2-integrin-mediated neutrophil adhesion at physical shear rates in vivo. Am J Physiol 263:H1034-H1044

    Google Scholar 

  39. Xu HS, Wang DJ, Pace RC, Jones RS (1992) Beneficial effect of prewarming the donor liver for rat liver transplantation. Am J Surg 163:164–168

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Surgical Research, Ludwig Maximilian's University, Klinikum Großhadern, Marchioninistrasse 15, D-81377, Munich, Germany

    Markus Rentsch

  2. Department of General Surgery, University of Geoettingen, Robert-Koch-Strasse 40, D-37075, Göttingen, Germany

    Stefan Post

  3. Department of Surgery, County Hospital Altoetting, Germany

    Pablo Palma

  4. Department of Physiological Siences, State University of Rio de Janeiro, Rio de Janeiro, Brazil

    Alberto P. Gonzalez & Konrad Messnier

  5. Department of Clinical-Experimental Surgery, University of Homburg/Saar, D-66 421, Homburg/Saar, Germany

    Michael D. Menger

Authors
  1. Markus Rentsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stefan Post
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pablo Palma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alberto P. Gonzalez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael D. Menger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Konrad Messnier
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Rentsch, M., Post, S., Palma, P. et al. Intravital studies on beneficial effects of warm Ringer's lactate rinse in liver transplantation. Transpl Int 9, 461–467 (1996). https://doi.org/10.1007/BF00336823

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00336823

Key words

Search

Navigation