REVIEW

The influence of brain death on donor liver and the potential mechanisms of protective intervention

  • Shui-Jun ZHANG ,
  • Tao WANG
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  • The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

Received date: 03 Aug 2010

Accepted date: 28 Dec 2010

Published date: 05 Mar 2011

Copyright

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

Brain-dead donors have become one of the main sources of organs for transplantation in Western countries. The quality of donor organs is closely related to the outcome of the transplantation. Experimental studies have confirmed the inferior graft survival of livers from brain-dead donors compared with those from living donors. Studies conducted in the past 10 years have shown that brain death is associated with effects on the decreased donor organ quality. However, whether the decrease in the viability of donor organs is caused by brain death or by the events before and after brain death remains uncertain. The purpose of this review is to introduce the advances and controversies regarding the influence of brain death on the viability of donor livers and to summarize the mechanisms of the different protective interventions for donor livers.

Key words: brain death; donor liver

Cite this article

Shui-Jun ZHANG , Tao WANG . The influence of brain death on donor liver and the potential mechanisms of protective intervention[J]. Frontiers of Medicine, 2011 , 5(1) : 8 -14 . DOI: 10.1007/s11684-011-0109-y

1
van der Hoeven J A B, Ter Horst G J, Molema G, de Vos P, Girbes A R, Postema F, Freund R L, Wiersema J, van Schilfgaarde R, Ploeg R J. Effects of brain death and hemodynamic status on function and immunologic activation of the potential donor liver in the rat. Ann Surg, 2000, 232(6): 804–813

DOI PMID

2
Pratschke J, Wilhelm M J, Kusaka M, Basker M, Cooper D K, Hancock W W, Tilney N L. Brain death and its influence on donor organ quality and outcome after transplantation. Transplantation, 1999, 67(3): 343–348

DOI PMID

3
Bugge J F. Brain death and its implications for management of the potential organ donor. Acta Anaesthesiol Scand, 2009, 53(10): 1239–1250

DOI PMID

4
Chen E P, Bittner H B, Kendall S W, Van Trigt P. Hormonal and hemodynamic changes in a validated animal model of brain death. Crit Care Med, 1996, 24(8): 1352–1359

DOI PMID

5
Wilhelm M J, Pratschke J, Laskowski I A, Paz D M, Tilney N L. Brain death and its impact on the donor heart-lessons from animal models. J Heart Lung Transplant, 2000, 19(5): 414–418

DOI PMID

6
Novitzky D. Selection and management of cardiac allograft donors. Curr Opin Cardiol, 1996, 11(2): 174–182

DOI PMID

7
Rona G. Catecholamine cardiotoxicity. J Mol Cell Cardiol, 1985, 17(4): 291–306

DOI PMID

8
Novitzky D, Wicomb W N, Cooper D K, Rose A G, Reichart B. Prevention of myocardial injury during brain death by total cardiac sympathectomy in the Chacma baboon. Ann Thorac Surg, 1986, 41(5): 520–524

DOI PMID

9
Novitzky D, Rose A G, Cooper D K. Injury of myocardial conduction tissue and coronary artery smooth muscle following brain death in the baboon. Transplantation, 1988, 45(5): 964–966

DOI PMID

10
Shivalkar B, Van Loon J, Wieland W, Tjandra-Maga T B, Borgers M, Plets C, Flameng W. Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function. Circulation, 1993, 87(1): 230–239

PMID

11
Satur C M, Martin W, Darracott-Cankovic S, Morrison J, Wheatley D J. An experimental method to induce variable patterns of brain death and myocardial injury. Transplant Proc, 1998, 30(1): 211–213

DOI PMID

12
De Luca F A, Cruz R J Jr, Garrido Adel P, Prist R, Rocha-E-Silva M. Initial hepatosplanchnic blood flow distribution and oxygen metabolism in experimental model of hypotensive brain death. Ann Transplant, 2009, 14(1): 38–46

PMID

13
Steinhoff G, Behrend M, Schrader B, Duijvestijn A M, Wonigeit K. Expression patterns of leukocyte adhesion ligand molecules on human liver endothelia. Lack of ELAM-1 and CD62 inducibility on sinusoidal endothelia and distinct distribution of VCAM-1, ICAM-1, ICAM-2, and LFA-3. Am J Pathol, 1993, 142(2): 481–488

PMID

14
Steinhoff G, Brandt M. Adhesion molecules in liver transplantation. Hepatogastroenterology, 1996, 43(11): 1117–1123

PMID

15
Hoffmann M W, Wonigeit K, Steinhoff G, Herzbeck H, Flad H D, Pichlmayr R. Production of cytokines (TNF-alpha, IL-1-beta) and endothelial cell activation in human liver allograft rejection. Transplantation, 1993, 55(2): 329–335

DOI PMID

16
Omura T, Ishikura H, Nakajima Y, Kimura J, Ito K, Isai H, Tamatani T, Miyasaka M, Yoshiki T, Uchino J. The expression of LFA-1/ICAM-1 in liver transplantation in rats. Transplant Proc, 1992, 24(4): 1618–1619

PMID

17
Kuecuek O, Mantouvalou L, Klemz R, Kotsch K, Volk H D, Jonas S, Wesslau C, Tullius S, Neuhaus P, Pratschke J. Significant reduction of proinflammatory cytokines by treatment of the brain-dead donor. Transplant Proc, 2005, 37(1): 387–388

DOI PMID

18
Olinga P, van der Hoeven J A B, Merema M T, Freund R L, Ploeg R J, Groothuis G M. The influence of brain death on liver function. Liver Int, 2005, 25(1): 109–116

DOI PMID

19
Weiss S, Kotsch K, Francuski M, Reutzel-Selke A, Mantouvalou L, Klemz R, Kuecuek O, Jonas S, Wesslau C, Ulrich F, Pascher A, Volk H D, Tullius S G, Neuhaus P, Pratschke J. Brain death activates donor organs and is associated with a worse I/R injury after liver transplantation. Am J Transplant, 2007, 7(6): 1584–1593

DOI PMID

20
Zhang S, Zhu C, Wu Y, Zhai W, Shi J, Song Y, Li J, Li Z, Zhang G. Brain death affects the hepatic immunogenicity of pigs. Transplant Proc, 2008, 40(7): 2159–2162

DOI PMID

21
Pratschke J, Neuhaus P, Tullius S G. What can be learned from brain-death models? Transpl Int, 2005, 18(1): 15–21

DOI PMID

22
van der Hoeven J A, Moshage H, Schuurs T, Nijboer M, Van Schilfgaarde R, Ploeg R J. Brain death induces apoptosis in donor liver of the rat. Transplantation, 2003, 76(8): 1150–1154

DOI PMID

23
Pérez López S, Vázquez Moreno N, Escudero Augusto D, Astudillo González A, Alvarez Menéndez F, Goyache Goñi F, Otero Hernández J. A molecular approach to apoptosis in the human heart during brain death. Transplantation, 2008, 86(7): 977–982

DOI PMID

24
Adrie C, Monchi M, Fulgencio J P, Cottias P, Haouache H, Alvarez-Gonzalvez A, Guerrini P, Cavaillon J M, Adib-Conquy M. Immune status and apoptosis activation during brain death. Shock, 2010, 33(4): 353–362

DOI PMID

25
Patel T, Gores G J. Apoptosis and hepatobiliary disease. Hepatology, 1995, 21(6): 1725–1741

PMID

26
Daemen M A, van ’t Veer C, Denecker G, Heemskerk V H, Wolfs T G, Clauss M, Vandenabeele P, Buurman W A. Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation. J Clin Invest, 1999, 104(5): 541–549

DOI PMID

27
Nagareda T, Kinoshita Y, Tanaka A, Hasuike Y, Terada N, Nishizawa Y, Fujita M Q, Kuroda H, Yawata K, Aozasa K, Sakano T S U T O M U, Sugimoto T S U Y O S H I, Kotoh K I Y O S H I. Clinicopathological study of livers from brain-dead patients treated with a combination of vasopressin and epinephrine. Transplantation, 1989, 47(5): 792–797

DOI PMID

28
Novitzky D. Detrimental effects of brain death on the potential organ donor. Transplant Proc, 1997, 29(8): 3770–3772

DOI PMID

29
van der Hoeven J A, Lindell S, van Schilfgaarde R, Molema G, Ter Horst G J, Southard J H, Ploeg R J. Donor brain death reduces survival after transplantation in rat livers preserved for 20 hr. Transplantation, 2001, 72(10): 1632–1636

DOI PMID

30
Okamoto S, Corso C O, Nolte D, Rascher W, Thiery J, Yamaoka Y, Messmer K. Impact of brain death on hormonal homeostasis and hepatic microcirculation of transplant organ donors. Transpl Int, 1998, 11 (Suppl 1): S404–S407

PMID

31
Lin H, Yamamoto Y, Okamoto R, Ueda J, Yamamoto S, Mori K, Tanaka K, Yamaoka Y, Ozawa K. Hepatic functional difference between brain death hypotension and hypovolemic hypotension in liver donation. Transplant Proc, 1989, 21(1 Pt 2): 2389–2391

PMID

32
Toyama H, Takada M, Suzuki Y, Kuroda Y. Brain death-induced expression of ICAM-1 and VCAM-1 on rat hepatocytes. Hepatogastroenterology, 2003, 50(54): 1854–1856

PMID

33
Jassem W, Koo D D, Cerundolo L, Rela M, Heaton N D, Fuggle S V. Leukocyte infiltration and inflammatory antigen expression in cadaveric and living-donor livers before transplant. Transplantation, 2003, 75(12): 2001–2007

DOI PMID

34
Zhang S J, Zhai W L, Song Y, Shi J H, Li Z H, Li J, Chen S H. How brain-dead state affects the hepatic morphology and function of Ba-Ma mini pigs and its mechanism. Zhonghua Yi Xue Za Zhi, 2006, 86(18): 1244–1248 (in Chinese)

PMID

35
Compagnon P, Wang H, Lindell S L, Ametani M S, Mangino M J, D’Alessandro A M, Southard J H. Brain death does not affect hepatic allograft function and survival after orthotopic transplantation in a canine model. Transplantation, 2002, 73(8): 1218–1227

DOI PMID

36
Golling M, Mehrabi A, Blum K, Jahnke C, Kellner H, Bud O, Hashemi B, Breitkreutz R, Becker-Brandenburg K, Schemmer P, Gebhard M M, Herfarth C, Kraus T. Effects of hemodynamic instability on brain death-induced prepreservation liver damage. Transplantation, 2003, 75(8): 1154–1159

DOI PMID

37
Novitzky D, Cooper D K, Morrell D, Isaacs S. Change from aerobic to anaerobic metabolism after brain death, and reversal following triiodothyronine therapy. Transplantation, 1988, 45(1): 32–36

DOI PMID

38
Zhu C, Li J, Zhang G, Zhang Y, Zhai W, Shi J, Li Z, Li J, Zhang S. Brain death disrupts structure and function of pig liver. Transplant Proc, 2010, 42(3): 733–736

DOI PMID

39
Kusaka M, Pratschke J, Wilhelm M J, Ziai F, Zandi-Nejad K, Mackenzie H S, Hancock W W, Tilney N L. Activation of inflammatory mediators in rat renal isografts by donor brain death. Transplantation, 2000, 69(3): 405–410

DOI PMID

40
Pratschke J, Kofla G, Wilhelm M J, Vergopoulos A, Laskowski I, Shaw G D, Tullius S G, Volk H D, Neuhaus P, Tilney N L. Improvements in early behavior of rat kidney allografts after treatment of the brain-dead donor. Ann Surg, 2001, 234(6): 732–740

DOI PMID

41
Wu L W, He X S, Tai Q, Ju W Q, Ma Y, Wang D P, Zhu X F, Huang J F. Comparison of the short—term outcomes of liver transplant recipients receiving liver graft from brain-death and non-heart-beating donors. Nanfang Yi Ke Da Xue Xue Bao, 2008, 28(12): 2204–2206 (in Chinese)

42
Dubbeld J, Hoekstra H, Farid W, Ringers J, Porte R J, Metselaar H J, Baranski A G, Kazemier G, van den Berg A P, van Hoek B. Similar liver transplantation survival with selected cardiac death donors and brain death donors. Br J Surg, 2010, 97(5): 744–753

DOI PMID

43
Koo D D, Welsh K I, McLaren A J, Roake J A, Morris P J, Fuggle S V. Cadaver versus living donor kidneys: impact of donor factors on antigen induction before transplantation. Kidney Int, 1999, 56(4): 1551–1559

DOI PMID

44
Kim Y S, Lim C S, Kim S, Lee J S, Lee S, Kim S T, Kim H J, Chae D W. Cadaveric renal allograft at the time of implantation has the similar immunological features with the rejecting allograft. Transplantation, 2000, 70(7): 1080–1085

DOI PMID

45
Schwarz C, Regele H, Steininger R, Hansmann C, Mayer G, Oberbauer R. The contribution of adhesion molecule expression in donor kidney biopsies to early allograft dysfunction. Transplantation, 2001, 71(11): 1666–1670

DOI PMID

46
Fuggle S V, Koo D D. Cell adhesion molecules in clinical renal transplantation. Transplantation, 1998, 65(6): 763–769

DOI PMID

47
Takada M, Nadeau K C, Hancock W W, Mackenzie H S, Shaw G D, Waaga A M, Chandraker A, Sayegh M H, Tilney N L. Effects of explosive brain death on cytokine activation of peripheral organs in the rat. Transplantation, 1998, 65(12): 1533–1542

DOI PMID

48
Choi A M, Alam J. Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am J Respir Cell Mol Biol, 1996, 15(1): 9–19

PMID

49
Maines M D. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J, 1988, 2(10): 2557–2568

PMID

50
Maines M D. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol, 1997, 37(1): 517–554

DOI PMID

51
Kotsch K, Ulrich F, Reutzel-Selke A, Pascher A, Faber W, Warnick P, Hoffman S, Francuski M, Kunert C, Kuecuek O, Schumacher G, Wesslau C, Lun A, Kohler S, Weiss S, Tullius S G, Neuhaus P, Pratschke J. Methylprednisolone therapy in deceased donors reduces inflammation in the donor liver and improves outcome after liver transplantation: a prospective randomized controlled trial. Ann Surg, 2008, 248(6): 1042–1050

DOI PMID

52
van der Woude F J, Schnuelle P, Yard B A. Preconditioning strategies to limit graft immunogenicity and cold ischemic organ injury. J Investig Med, 2004, 52(5): 323–329

DOI PMID

53
Yard B, Beck G, Schnuelle P, Braun C, Schaub M, Bechtler M, Göttmann U, Xiao Y, Breedijk A, Wandschneider S, Lösel R, Sponer G, Wehling M, van der Woude F J. Prevention of cold-preservation injury of cultured endothelial cells by catecholamines and related compounds. Am J Transplant, 2004, 4(1): 22–30

DOI PMID

54
Zhang S J, Shi J H, Tang Z H, Wu Y, Zhai W L, Li Z H. The protection effects of glycine pretreatment on brain-dead donor liver. Zhonghua Qi Guan Yi Zhi Za Zhi, 2004, 25(5): 264–266 (in Chinese)

55
Wheeler M D, Ikejema K, Enomoto N, Stacklewitz R F, Seabra V, Zhong Z, Yin M, Schemmer P, Rose M L, Rusyn I, Bradford B, Thurman R G. Glycine: a new anti-inflammatory immunonutrient. Cell Mol Life Sci, 1999, 56(9-10): 843–856

DOI PMID

56
Schemmer P, Bradford B U, Rose M L, Bunzendahl H, Raleigh J A, Lemasters J J, Thurman R G. Intravenous glycine improves survival in rat liver transplantation. Am J Physiol, 1999, 276(4 Pt 1): G924–G932

57
Li J, Zhang S, Wu Y, Guo W, Zhang Y, Zhai W. Protective effects of N-acetylcysteine on the liver of brain-dead Ba-Ma mini pig. Transplant Proc, 2010, 42(1): 195–199

DOI PMID

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