- Research Institute of General Surgery， Nanjing General Hospital of Nanjing Military Command of PLA， Nanjing University School of Medicine， Nanjing 210002， Jiangsu Province， China;
LI Yousheng,
Email: liys@medmail.com.cn
Objective To investigate development and perspectives of brain death donation and transplantation.
Methods The related literatures about the research of brain dead donors were reviewed.
Results Brain death effects hemodynamic stability， hormonal changes， neuroimmunologic effects，and unleashes a cascade of inflammatory events， which may affect quality of graft， graft survival， and patient outcome. Moreover， the exact mechanism linked to brain death is incompletely understood.
Conclusions The pathological physiology changes of brain dead donors has important impact on graft outcomes. However， subsequent work remains to be done.
Citation： GUO Mingxiao,LI Yousheng,.. Development and Perspectives of Brain Death Donation and Transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(10): 1183-1187. doi: Copy
| 1. | A definition of irreversible coma. Report of the Ad Hoc Committeeof the Harvard Medical School to Examine the Definition of Brain Death[J]. JAMA， 1968， 205(6)：337-340. |
| 2. | Wijdicks EFM， Varelas PN， Gronseth GS， et al. Evidence-based guideline update：determining brain death in adults：report of the quality standards subcommittee of the American Academy of Neurology[J]. Neurology， 2010， 74(3)：1911-1918. |
| 3. | Bugge JF. Brain death and its implications for management of the potential organ donor[J]. Acta Anaesthesiol Scand，2009，53(10)：1239-1250. |
| 4. | Belzberg H， ShoemakerWC， Wo CC， et al. Hemodynamic andoxygen transport patterns after head trauma and brain death：impli-cations for management of the organ donor[J]. J Trauma， 2007，. |
| 5. | Nakagawa K， Tang JF. Physiologic response of human brain death and the use of vasopressin for successful organ transplantation[J]. J Clin Anesth，2011， 23(2)：145-148. |
| 6. | Miñambres E， Cemborain A， Sánchez-Velasco P， et al. Correlationbetween transcranial interleukin-6 gradient and outcome in patientswith acute brain injury[J]. Crit Care Med， 2003， 31(3)：933-938. |
| 7. | de Vries DK， Lindeman JH， Ringers J， et al. Donor brain death predisposes human kidney grafts to a proinflammatory reaction after transplantation[J]. Am J Transplant，2011，11(5)：1064-1070. |
| 8. | Okamoto S， Corso CO， Leiderer R， et al. Role of hypotension in brain-death associated impairment of liver microcirculation and viability[J]. Transpl Int， 2000， 13(6)：428-435. |
| 9. | Van Der Hoeven JA， Moshage H， Schuurs T， et al. Brain death induces apoptosis in donor liver of the rat[J]. Transplantation， 2003， 76(8)：1150-1154. |
| 10. | Koudstaal LG， ’t Hart NA， Ottens PJ， et al. Brain death induces inflammation in the donor intestine[J]. Transplantation， 2008，86(1)：148-154. |
| 11. | Morariu AM， Schuurs TA， Leuvenink HG， et al. Early events in kidney donation：progression of endothelial activation，oxidative stress and tubular injury after brain death[J]. Am J Transplant， 2008， 8(5)：933-941. |
| 12. | Apostolakis E， Parissis H， Dougenis D. Brain death and donor heart dysfunction：implications in cardiac transplantation[J]. J Card Surg， 2010， 25(1)：98-106. |
| 13. | Zweers N， Petersen AH， van der Hoeven JA， et al. Donor brain death aggravates chronic rejection after lung transplantation in rats[J]. Transplantation， 2004， 78(9)：1251-1258. |
| 14. | Viemann D， Strey A， Janning A， et al. Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells[J]. Blood， 2005， 105(7)：2955-2962. |
| 15. | Bouma HR， Ploeg RJ， Schuurs TA， et al. Signal transduction pathways involved in brain death–induced renal injury[J]. Am J Transplant， 2009， 9(5)：989-997. |
| 16. | Kusaka M， Kuroyanagi Y， Kowa H. Genomewide expression profiles of rat model renal isografts from brain dead donors[J]. Transplantation， 2007， 83(1)：62-70. |
| 17. | Atkinson C，Floerchinger B，Qiao F， et al. Donor brain death exacerbates complement-dependent ischemia/reperfusion injury in transplanted hearts[J]. Circulation， 2013， 127(12)：1290-1299. |
| 18. | Atkinson C， Varela JC， Tomlinson S. Complement-dependent inflammation and injury in a murine model of brain dead donor hearts[J]. Circ Res， 2009， 105(11)：1094-1101. |
| 19. | Damman J， Nijboer WN， Schuurs TA， et al. Local renal complement C3 induction by donor brain death is associated with reduced renal allograft function after transplantation[J]. Nephrol Dial Transplant， 2011， 26(7)：2345-2354. |
| 20. | Zhang J， Jiang R， Liu L， et al. Traumatic brain injury-associated coagulopathy[J]. J Neurotrauma， 2012， 29(17)：2597-2605. |
| 21. | lznerowicz A， Chudoba P， Kamińska D， et al. Duration of brain death and cold ischemia time，but not warm ischemia time，increases expression of genes associated with apoptosis in transplanted kidneys from deceased donors[J]. Transplant Proc， 2011， 43(8)：2887-2890. |
| 22. | Kamińska D， Kościelska-Kasprzak K， Drulis-Fajdasz D， et al. Kidney ischemic injury genes expressed after donor brain death are predictive for the outcome of kidney transplantation?[J]. Transplant Proc， 2011， 43(8)：2891-2894. |
| 23. | van Werkhoven MB， Damman J， van Dijk MC， et al. Complement mediated renal inflammation induced by donor brain death：role of renal C5a-C5aR interaction[J]. Am J Transplant， 2013，13(4)：875-882. |
| 24. | Nijboer WN， Schuurs TA， van der Hoeven JA， et al. Effect of brain death on gene expression and tissue activation in humandonor kidneys[J]. Transplantation， 2004， 78(7)：978-986. |
| 25. | Nagaraja P， Roberts GW， Stephens M， et al. Influence of delayed graft function and acute rejection on outcomes after kidney transplantation from donors after cardiac death[J]. Transplantation， 2012， 94(12)：1218-1223. |
| 26. | Reich DJ，Guy SR. Donation after cardiac death in abdominalorgan transplantation[J]. Mt Sinai J Med， 2012， 79(3)：365-375. |
| 27. | Apostolakis E，Parissis H， Dougenis D. Brain death and donor heart dysfunction：implications in cardiac transplantation[J]. J Card Surg， 2010， 25(1)：98-106. |
| 28. | Pérez López S， Vázquez Moreno N， Escudero Augusto D， et al. A molecular approach to apoptosis in the human heart during brain death[J]. Transplantation， 2008， 86(7)：977-982. |
| 29. | Mehra MR， Uber PA， Ventura HO， et al. The impact of mode of donor brain death on cardiac allograft vasculopathy：an intravascularultrasound study[J]. J Am Coll Cardiol， 2004， 43(5)：806-810. |
| 30. | Cohen O， De La Zerda DJ， Beygui R， et al. Donor brain death mechanisms and outcomes after heart transplantation[J]. Transplantation Proc， 2007， 39(10)：2964-2969. |
| 31. | Luckraz H， Charman SC， Parameshwar J， et al. Are non-brain stem-dead cardiac donors acceptable donors?[J]. J Heart Lung Transplant， 2004， 23(3)：330-333. |
| 32. | Anyanwu AC， Banner NR， Mitchell AG， et al. Low incidence and severity of transplant-associated coronary artery disease in heart transplants from live donors[J]. J Heart Lung Transplant， 2003， 22(3)：281-286. |
| 33. | Chang WJ， Chang YH， Toledo-Pereyra LH. The challenge behindbrain death organ transplantation in liver ischemia and reperfusion injury[J]. J Surg Res， 2013， 180(2)：250-251. |
| 34. | Zhang SJ， Wang T. The influence of brain death on donor liver and the potential mechanisms of protective intervention[J]. Front Med， 2011， 5(1)：8-14. |
| 35. | Vanatta JM， Dean AG， Hathaway DK， et al. Liver transplant usingdonors after cardiac death：a single-center approach providing outcomes comparable to donation after brain death[J]. Exp Clin Transplant， 2013， 11(2)：154-163. |
| 36. | Meurisse N， Vanden Bussche S， Jochmans I，et al. Outcomes of liver transplantations using donations after circulatory death：a single-center experience[J]. Transplant Proc， 2012， 44(9)：2868-2873. |
| 37. | Sammani S， Park KS， Zaidi SR， et al. A sphingosine 1-phosphate 1 receptor agonist modulates brain death-induced neurogenic pulmonary injury[J]. Am J Respir Cell Mol Biol， 2011， 45(5)：1022-1027. |
| 38. | Wauters S， Verleden GM， Belmans A， et al. Donor cause of brain death and related time intervals：does it affect outcome after lung transplantation?[J]. Eur J Cardiothorac Surg， 2011， 39(4)：e68-e76. |
| 39. | Kang CH， Anraku M， Cypel M， et al. Transcriptional signatures in donor lungs from donation after cardiac death vs after brain death：a functional pathway analysis[J]. J Heart Lung Transplant， 2011， 30(3)：289-298. |
| 40. | Mateos Rodríguez AA， Navalpotro Pascual JM， del Río GallegosF. Lung transplant of extrahospitalary donor after cardiac death[J].Am J Emerg Med， 2013， 31(4)：710-711. |
| 41. | Levvey BJ， Harkess M， Hopkins P， et al. Excellent clinical outcomes from a national donation-after-determination-of-cardiac-death lung transplant collaborative[J]. Am J Transplant， 2012，12(9)：2406-2413. |
| 42. | Lam L， Inaba K， Branco BC， et al. The impact of early hormonaltherapy in catastrophic brain-injured patients and its effect on organprocurement[J]. Am Surg， 2012， 78(3)：318-324. |
| 43. | Kotsch K， Ulrich F， Reutzel-Selke A， et al. Methylprednisolone therapy in deceased donors reduces inflammation in the donor liverand improves outcome after liver transplantation：a prospectiverandomized controlled trial[J]. Ann Surg， 2008， 248(6)：1042-1050. |
| 44. | Follette DM， Rudich SM， Babcock WD， et al. Improved oxygenation and increased lung donor recovery with high-dose steroid administration after brain death[J]. J Heart Lung Transplant， 1998， 17(4)：423-429. |
| 45. | Schnuelle P， Berger S， De Boer J， et al. Effects of catecholamine application to brain-dead donors on graft survival in solid organ transplantation[J]. Transplantation， 2001， 72(3)：455-463. |
| 46. | Schnuelle P， Gottmann U， Hoeger S， et al. Effects of donor pret-reatment with dopamine on graft function after kidney transplantation[J]. JAMA， 2009， 302(10)：1067-1075. |
| 47. | Nijboer WN， Ottens PJ， van Dijk A， et al. Donor pretreatment with carbamylated erythropoietin in a brain death model reduces inflammation more effectively than erythropoietin while preservingrenal function[J]. Crit Care Med， 2010， 38(4)：1155-1161. |
| 48. | De Ferrari GM， Schwartz PJ. Vagus nerve stimulation：frompre-clinical to clinical application：challenges and future directions[J]. Heart Fail Rev， 2011， 16(2)：195-203. |
| 49. | Kämäräinen A， Virkkunen I， Tenhunen J. Hypothermic preconditioning of donor organs prior to harvesting and ischaemia using ice-cold intravenous fluids[J]. Med Hypotheses， 2009， 73(1)：65-66. |
| 50. | Kellum JA， Venkataraman R， Powner D， et al. Feasibility study of cytokine removal by hemoadsorption in brain-dead humans[J].Crit Care Med， 2008， 36(1)：268-272. |
| 51. | (5)：1032-1042. |
- 1. A definition of irreversible coma. Report of the Ad Hoc Committeeof the Harvard Medical School to Examine the Definition of Brain Death[J]. JAMA， 1968， 205(6)：337-340.
- 2. Wijdicks EFM， Varelas PN， Gronseth GS， et al. Evidence-based guideline update：determining brain death in adults：report of the quality standards subcommittee of the American Academy of Neurology[J]. Neurology， 2010， 74(3)：1911-1918.
- 3. Bugge JF. Brain death and its implications for management of the potential organ donor[J]. Acta Anaesthesiol Scand，2009，53(10)：1239-1250.
- 4. Belzberg H， ShoemakerWC， Wo CC， et al. Hemodynamic andoxygen transport patterns after head trauma and brain death：impli-cations for management of the organ donor[J]. J Trauma， 2007，.
- 5. Nakagawa K， Tang JF. Physiologic response of human brain death and the use of vasopressin for successful organ transplantation[J]. J Clin Anesth，2011， 23(2)：145-148.
- 6. Miñambres E， Cemborain A， Sánchez-Velasco P， et al. Correlationbetween transcranial interleukin-6 gradient and outcome in patientswith acute brain injury[J]. Crit Care Med， 2003， 31(3)：933-938.
- 7. de Vries DK， Lindeman JH， Ringers J， et al. Donor brain death predisposes human kidney grafts to a proinflammatory reaction after transplantation[J]. Am J Transplant，2011，11(5)：1064-1070.
- 8. Okamoto S， Corso CO， Leiderer R， et al. Role of hypotension in brain-death associated impairment of liver microcirculation and viability[J]. Transpl Int， 2000， 13(6)：428-435.
- 9. Van Der Hoeven JA， Moshage H， Schuurs T， et al. Brain death induces apoptosis in donor liver of the rat[J]. Transplantation， 2003， 76(8)：1150-1154.
- 10. Koudstaal LG， ’t Hart NA， Ottens PJ， et al. Brain death induces inflammation in the donor intestine[J]. Transplantation， 2008，86(1)：148-154.
- 11. Morariu AM， Schuurs TA， Leuvenink HG， et al. Early events in kidney donation：progression of endothelial activation，oxidative stress and tubular injury after brain death[J]. Am J Transplant， 2008， 8(5)：933-941.
- 12. Apostolakis E， Parissis H， Dougenis D. Brain death and donor heart dysfunction：implications in cardiac transplantation[J]. J Card Surg， 2010， 25(1)：98-106.
- 13. Zweers N， Petersen AH， van der Hoeven JA， et al. Donor brain death aggravates chronic rejection after lung transplantation in rats[J]. Transplantation， 2004， 78(9)：1251-1258.
- 14. Viemann D， Strey A， Janning A， et al. Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells[J]. Blood， 2005， 105(7)：2955-2962.
- 15. Bouma HR， Ploeg RJ， Schuurs TA， et al. Signal transduction pathways involved in brain death–induced renal injury[J]. Am J Transplant， 2009， 9(5)：989-997.
- 16. Kusaka M， Kuroyanagi Y， Kowa H. Genomewide expression profiles of rat model renal isografts from brain dead donors[J]. Transplantation， 2007， 83(1)：62-70.
- 17. Atkinson C，Floerchinger B，Qiao F， et al. Donor brain death exacerbates complement-dependent ischemia/reperfusion injury in transplanted hearts[J]. Circulation， 2013， 127(12)：1290-1299.
- 18. Atkinson C， Varela JC， Tomlinson S. Complement-dependent inflammation and injury in a murine model of brain dead donor hearts[J]. Circ Res， 2009， 105(11)：1094-1101.
- 19. Damman J， Nijboer WN， Schuurs TA， et al. Local renal complement C3 induction by donor brain death is associated with reduced renal allograft function after transplantation[J]. Nephrol Dial Transplant， 2011， 26(7)：2345-2354.
- 20. Zhang J， Jiang R， Liu L， et al. Traumatic brain injury-associated coagulopathy[J]. J Neurotrauma， 2012， 29(17)：2597-2605.
- 21. lznerowicz A， Chudoba P， Kamińska D， et al. Duration of brain death and cold ischemia time，but not warm ischemia time，increases expression of genes associated with apoptosis in transplanted kidneys from deceased donors[J]. Transplant Proc， 2011， 43(8)：2887-2890.
- 22. Kamińska D， Kościelska-Kasprzak K， Drulis-Fajdasz D， et al. Kidney ischemic injury genes expressed after donor brain death are predictive for the outcome of kidney transplantation?[J]. Transplant Proc， 2011， 43(8)：2891-2894.
- 23. van Werkhoven MB， Damman J， van Dijk MC， et al. Complement mediated renal inflammation induced by donor brain death：role of renal C5a-C5aR interaction[J]. Am J Transplant， 2013，13(4)：875-882.
- 24. Nijboer WN， Schuurs TA， van der Hoeven JA， et al. Effect of brain death on gene expression and tissue activation in humandonor kidneys[J]. Transplantation， 2004， 78(7)：978-986.
- 25. Nagaraja P， Roberts GW， Stephens M， et al. Influence of delayed graft function and acute rejection on outcomes after kidney transplantation from donors after cardiac death[J]. Transplantation， 2012， 94(12)：1218-1223.
- 26. Reich DJ，Guy SR. Donation after cardiac death in abdominalorgan transplantation[J]. Mt Sinai J Med， 2012， 79(3)：365-375.
- 27. Apostolakis E，Parissis H， Dougenis D. Brain death and donor heart dysfunction：implications in cardiac transplantation[J]. J Card Surg， 2010， 25(1)：98-106.
- 28. Pérez López S， Vázquez Moreno N， Escudero Augusto D， et al. A molecular approach to apoptosis in the human heart during brain death[J]. Transplantation， 2008， 86(7)：977-982.
- 29. Mehra MR， Uber PA， Ventura HO， et al. The impact of mode of donor brain death on cardiac allograft vasculopathy：an intravascularultrasound study[J]. J Am Coll Cardiol， 2004， 43(5)：806-810.
- 30. Cohen O， De La Zerda DJ， Beygui R， et al. Donor brain death mechanisms and outcomes after heart transplantation[J]. Transplantation Proc， 2007， 39(10)：2964-2969.
- 31. Luckraz H， Charman SC， Parameshwar J， et al. Are non-brain stem-dead cardiac donors acceptable donors?[J]. J Heart Lung Transplant， 2004， 23(3)：330-333.
- 32. Anyanwu AC， Banner NR， Mitchell AG， et al. Low incidence and severity of transplant-associated coronary artery disease in heart transplants from live donors[J]. J Heart Lung Transplant， 2003， 22(3)：281-286.
- 33. Chang WJ， Chang YH， Toledo-Pereyra LH. The challenge behindbrain death organ transplantation in liver ischemia and reperfusion injury[J]. J Surg Res， 2013， 180(2)：250-251.
- 34. Zhang SJ， Wang T. The influence of brain death on donor liver and the potential mechanisms of protective intervention[J]. Front Med， 2011， 5(1)：8-14.
- 35. Vanatta JM， Dean AG， Hathaway DK， et al. Liver transplant usingdonors after cardiac death：a single-center approach providing outcomes comparable to donation after brain death[J]. Exp Clin Transplant， 2013， 11(2)：154-163.
- 36. Meurisse N， Vanden Bussche S， Jochmans I，et al. Outcomes of liver transplantations using donations after circulatory death：a single-center experience[J]. Transplant Proc， 2012， 44(9)：2868-2873.
- 37. Sammani S， Park KS， Zaidi SR， et al. A sphingosine 1-phosphate 1 receptor agonist modulates brain death-induced neurogenic pulmonary injury[J]. Am J Respir Cell Mol Biol， 2011， 45(5)：1022-1027.
- 38. Wauters S， Verleden GM， Belmans A， et al. Donor cause of brain death and related time intervals：does it affect outcome after lung transplantation?[J]. Eur J Cardiothorac Surg， 2011， 39(4)：e68-e76.
- 39. Kang CH， Anraku M， Cypel M， et al. Transcriptional signatures in donor lungs from donation after cardiac death vs after brain death：a functional pathway analysis[J]. J Heart Lung Transplant， 2011， 30(3)：289-298.
- 40. Mateos Rodríguez AA， Navalpotro Pascual JM， del Río GallegosF. Lung transplant of extrahospitalary donor after cardiac death[J].Am J Emerg Med， 2013， 31(4)：710-711.
- 41. Levvey BJ， Harkess M， Hopkins P， et al. Excellent clinical outcomes from a national donation-after-determination-of-cardiac-death lung transplant collaborative[J]. Am J Transplant， 2012，12(9)：2406-2413.
- 42. Lam L， Inaba K， Branco BC， et al. The impact of early hormonaltherapy in catastrophic brain-injured patients and its effect on organprocurement[J]. Am Surg， 2012， 78(3)：318-324.
- 43. Kotsch K， Ulrich F， Reutzel-Selke A， et al. Methylprednisolone therapy in deceased donors reduces inflammation in the donor liverand improves outcome after liver transplantation：a prospectiverandomized controlled trial[J]. Ann Surg， 2008， 248(6)：1042-1050.
- 44. Follette DM， Rudich SM， Babcock WD， et al. Improved oxygenation and increased lung donor recovery with high-dose steroid administration after brain death[J]. J Heart Lung Transplant， 1998， 17(4)：423-429.
- 45. Schnuelle P， Berger S， De Boer J， et al. Effects of catecholamine application to brain-dead donors on graft survival in solid organ transplantation[J]. Transplantation， 2001， 72(3)：455-463.
- 46. Schnuelle P， Gottmann U， Hoeger S， et al. Effects of donor pret-reatment with dopamine on graft function after kidney transplantation[J]. JAMA， 2009， 302(10)：1067-1075.
- 47. Nijboer WN， Ottens PJ， van Dijk A， et al. Donor pretreatment with carbamylated erythropoietin in a brain death model reduces inflammation more effectively than erythropoietin while preservingrenal function[J]. Crit Care Med， 2010， 38(4)：1155-1161.
- 48. De Ferrari GM， Schwartz PJ. Vagus nerve stimulation：frompre-clinical to clinical application：challenges and future directions[J]. Heart Fail Rev， 2011， 16(2)：195-203.
- 49. Kämäräinen A， Virkkunen I， Tenhunen J. Hypothermic preconditioning of donor organs prior to harvesting and ischaemia using ice-cold intravenous fluids[J]. Med Hypotheses， 2009， 73(1)：65-66.
- 50. Kellum JA， Venkataraman R， Powner D， et al. Feasibility study of cytokine removal by hemoadsorption in brain-dead humans[J].Crit Care Med， 2008， 36(1)：268-272.
- 51. (5)：1032-1042.