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.
. The influence of brain death on donor liver and the potential mechanisms of protective intervention[J]. Frontiers of Medicine, 2011, 5(1): 8-14.
Shui-Jun ZHANG, Tao WANG. The influence of brain death on donor liver and the potential mechanisms of protective intervention. Front Med, 2011, 5(1): 8-14.
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: 10.1097/00000658-200012000-00009 pmid:11088075
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: 10.1097/00007890-199902150-00001 pmid:10030276
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: 10.1111/j.1399-6576.2009.02064.x pmid:19681785
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: 10.1097/00003246-199608000-00014 pmid:8706491
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: 10.1016/S1053-2498(00)00073-5 pmid:10808147
6
Novitzky D. Selection and management of cardiac allograft donors. Curr Opin Cardiol , 1996, 11(2): 174–182 doi: 10.1097/00001573-199603000-00011 pmid:8736689
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: 10.1016/S0003-4975(10)63032-9 pmid:3707246
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: 10.1097/00007890-198805000-00025 pmid:3285543
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:8419012
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: 10.1016/S0041-1345(97)01233-5 pmid:9475003
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:19289995
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:8434643
14
Steinhoff G, Brandt M. Adhesion molecules in liver transplantation. Hepatogastroenterology , 1996, 43(11): 1117–1123 pmid:8908538
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: 10.1097/00007890-199302000-00019 pmid:8094579
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:1353922
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: 10.1016/j.transproceed.2004.12.165 pmid:15808654
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: 10.1111/j.1478-3231.2005.01035.x pmid:15698407
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: 10.1111/j.1600-6143.2007.01799.x pmid:17430397
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: 10.1016/j.transproceed.2008.06.053 pmid:18790180
21
Pratschke J, Neuhaus P, Tullius S G. What can be learned from brain-death models? Transpl Int , 2005, 18(1): 15–21 doi: 10.1111/j.1432-2277.2004.00018.x pmid:15612978
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: 10.1097/01.TP.0000080983.14161.95 pmid:14578744
23
Pérez López S, Vázquez Moreno N, Escudero Augusto D, Astudillo González A, Alvarez Menéndez F, Goyache Go?i F, Otero Hernández J. A molecular approach to apoptosis in the human heart during brain death. Transplantation , 2008, 86(7): 977–982 doi: 10.1097/TP.0b013e318186d6d6 pmid:18852665
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: 10.1097/SHK.0b013e3181b65b99 pmid:20407403
25
Patel T, Gores G J. Apoptosis and hepatobiliary disease. Hepatology , 1995, 21(6): 1725–1741 pmid:7768518
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: 10.1172/JCI6974 pmid:10487768
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: 10.1097/00007890-198905000-00009 pmid:2718242
28
Novitzky D. Detrimental effects of brain death on the potential organ donor. Transplant Proc , 1997, 29(8): 3770–3772 doi: 10.1016/S0041-1345(97)01149-4 pmid:9414920
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: 10.1097/00007890-200111270-00009 pmid:11726822
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:9665027
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:2652778
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:14696418
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 12829901 doi: 10.1097/01.TP.0000061605.30685.03
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:16796882
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 11981412 doi: 10.1097/00007890-200204270-00006
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: 10.1097/01.TP.0000062868.34247.8F pmid:12717195
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: 10.1097/00007890-198801000-00008 pmid:3336918
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: 10.1016/j.transproceed.2010.02.028 pmid:20430159
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: 10.1097/00007890-200002150-00017 pmid:10706051
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: 10.1097/00000658-200112000-00004 pmid:11729379
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: 10.1002/bjs.7043 pmid:20393979
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: 10.1046/j.1523-1755.1999.00657.x pmid:10504507
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: 10.1097/00007890-200010150-00015 pmid:11045646
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: 10.1097/00007890-200106150-00028 pmid:11435980
46
Fuggle S V, Koo D D. Cell adhesion molecules in clinical renal transplantation. Transplantation , 1998, 65(6): 763–769 doi: 10.1097/00007890-199803270-00001 pmid:9539086
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: 10.1097/00007890-199806270-00001 pmid:9665067
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:8679227
49
Maines M D. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J , 1988, 2(10): 2557–2568 pmid:3290025
50
Maines M D. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol , 1997, 37(1): 517–554 doi: 10.1146/annurev.pharmtox.37.1.517 pmid:9131263
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: 10.1097/SLA.0b013e318190e70c pmid:19092349
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: 10.2310/6650.2004.00028 pmid:15551655
53
Yard B, Beck G, Schnuelle P, Braun C, Schaub M, Bechtler M, G?ttmann U, Xiao Y, Breedijk A, Wandschneider S, L?sel 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: 10.1046/j.1600-6143.2003.00268.x pmid:14678031
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: 10.1007/s000180050030 pmid:11212343
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: 10.1016/j.transproceed.2009.12.039 pmid:20172312
