Impact of human-derived hemoglobin based oxygen vesicles as a machine perfusion solution for liver donation after cardiac death in a pig model


Autoři: Tatsuya Shonaka aff001;  Naoto Matsuno aff001;  Hiromichi Obara aff002;  Ryo Yoshikawa aff002;  Yuji Nishikawa aff003;  Yo Ishihara aff001;  Hiroki Bochimoto aff004;  Mikako Gochi aff001;  Masahide Otani aff001;  Hiroyuki Kanazawa aff001;  Hiroshi Azuma aff005;  Hiromi Sakai aff006;  Hiroyuki Furukawa aff001
Působiště autorů: Department of Surgery, Asahikawa Medical University, Asahikawa-shi, Hokkaido, Japan aff001;  Department of Mechanical Engineering, Tokyo Metropolitan University, Hachioji-shi, Tokyo, Japan aff002;  Department of Pathology, Asahikawa Medical University, Asahikawa-shi, Hokkaido, Japan aff003;  Department of Cell Physiology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan aff004;  Department of Pediatrics, Asahikawa Medical University, Asahikawa-shi, Hokkaido, Japan aff005;  Department of Chemistry, Nara Medical University, Kashihara-shi, Nara, Japan aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226183

Souhrn

The recent clinical application of perfusion technology for the machine preservation of donation after cardiac death (DCD) grafts has some advantages. Oxygenation has been proposed for the preservation of DCD liver grafts. The aim of this study is to clarify whether the use of HbV-containing preservation solution during the subnormothermic machine perfusion (SNMP) of the liver graft improves the graft function of DCD porcine livers in an ex vivo reperfusion model. Pig livers were excised after 60 minutes of warm ischemic time and were preserved under one of three preservation conditions for 4 hours. The preservation conditions were as follows: 4°C cold storage (CS group; N = 5), Hypothermic machine preservation (HMP) with UW gluconate solution (HMP group; N = 5), SNMP (21°C) with UW gluconate solution (SNMP group; N = 5), SNMP (21°C) with HbVs (Hb; 1.8 mg/dl) perfusate (SNMP+HbV group; N = 5). Autologous blood perfusion was performed for 2 hours in an isolated liver reperfusion model (IRM). The oxygen consumption of the SNMP and SNMP+HbV group was higher than the HMP groups (p < 0.05). During the reperfusion, the AST level in the SNMP+HbV group was lower than that in the CS, HMP and SNMP groups. The changes in pH after reperfusion was significantly lower in SNMP+HbV group than CS and HMP groups. The ultrastructural findings indicated that the mitochondria of the SNMP+HbV group was well maintained in comparison to the CS, HMP and SNMP groups. The SNMP+HbVs preservation solution protected against metabolic acidosis and preserved the liver function after reperfusion injury in the DCD liver.

Klíčová slova:

Blood – Blood pressure – Hepatocytes – Liver transplantation – Mitochondria – Oxygen – Oxygen consumption – Reperfusion


Zdroje

1. Wolfe RA, Merion RM, Roys EC, Port FK. Trends in organ donation and transplantation in the United States, 1998–2007. Am J Transplant. 2009; 9(4 Pt 2):869–878. doi: 10.1111/j.1600-6143.2009.02564.x 19341412

2. Le Dinh H, de Roover A, Kaba A, Lauwick S, Joris J, Delwaide J, et al. Donation after cardio-circulatory death liver transplantation. World J Gastroenterol. 2012; 18: 4491–4506. doi: 10.3748/wjg.v18.i33.4491 22969222

3. Cursio R, Gugenheim J. Ischemia-Reperfusion Injury and Ischemic-Type Biliary Lesions following Liver Transplantation. J Transplant. 2012; 2012: 164329. doi: 10.1155/2012/164329 22530107

4. Seehofer D, Eurich D, Veltzke-Schlieker W, Neuhaus P. Biliary complications after liver transplantation: old problems and new challenges. Am J Transplant. 2013; 13: 253–265. doi: 10.1111/ajt.12034 23331505

5. Heidenhain C, Pratschke J, Puhl G, Neumann U, Pascher A, Veltzke-Schlieker W, et al. Incidence of and risk factors for ischemic-type biliary lesions following orthotopic liver transplantation. Transpl Int. 2010; 23: 14–22. doi: 10.1111/j.1432-2277.2009.00947.x 19691661

6. Guarrera JV, Henry SD, Samstein B, Odeh-Ramadan R, Kinkhabwala M, Goldstein MJ et al. Hypothermic machine preservation in human liver transplantation: the first clinical series. Am J Transplant. 2010; 10: 372–381. doi: 10.1111/j.1600-6143.2009.02932.x 19958323

7. Dutkowski P, Graf R, Clavien PA. Rescue of the cold preserved rat liver by hypothermic oxygenated machine perfusion. Am J Transplant. 2006; 6(5 Pt 1): 903–912. doi: 10.1111/j.1600-6143.2006.01264.x 16611326

8. Changani KK, Fuller BJ, Bryant DJ, Bell JD, Ala-Korpela M, Taylor-Robinson SD, et al. Non-invasive assessment of ATP regeneration potential of the preserved donor liver. A 31P MRS study in pig liver. J Hepatol. 1997; 26: 336–342. doi: 10.1016/s0168-8278(97)80050-5 9059955

9. Dutkowski P, Schlegel A, de Oliveira M, Müllhaupt B, Neff F, Clavien PA. HOPE for human liver grafts obtained from donors after cardiac death. J Hepatol. 2014; 60: 765–772. doi: 10.1016/j.jhep.2013.11.023 24295869

10. Fondevila C, Hessheimer AJ, Maathuis MH, Muñoz J, Taurá P, Calatayud D, et al. Superior preservation of DCD livers with continuous normothermic perfusion. Ann Surg. 2011; 254: 1000–1007. doi: 10.1097/SLA.0b013e31822b8b2f 21862925

11. op den Dries S, Karimian N, Sutton ME, Westerkamp AC, Nijsten MW, Gouw AS, et al. Ex vivo normothermic machine perfusion and viability testing of discarded human donor livers. Am J Transplant. 2013; 13: 1327–1335. doi: 10.1111/ajt.12187 23463950

12. Ravikumar R, Jassem W, Mergental H, Heaton N, Mirza D, Perera MT et al. Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial. Am J Transplant. 2016; 16: 1779–1787. doi: 10.1111/ajt.13708 26752191

13. Olschewski P, Gass P, Ariyakhagorn V, Jasse K, Hunold G, Menzel M, et al. The influence of storage temperature during machine perfusion on preservation quality of marginal donor livers. Cryobiology. 2010; 60: 337–343. doi: 10.1016/j.cryobiol.2010.03.005 20233587

14. Bruinsma BG, Yeh H, Ozer S, Martins PN, Farmer A, Wu W, et al. Subnormothermic machine perfusion for ex vivo preservation and recovery of the human liver for transplantation. Am J Transplant. 2014; 14: 1400–1449. doi: 10.1111/ajt.12727 24758155

15. Obara H, Matsuno N, Shigeta T, Enosawa S, Hirano T, Mizunuma H. Rewarming machine perfusion system for liver transplantation. J Med Device. 2013; 7: 1–7.

16. Sakai H. Overview of Potential Clinical Applications of Hemoglobin Vesicles (HbV) as Artificial Red Cells, Evidenced by Preclinical Studies of the Academic Research Consortium. J Funct Biomater. 2017 Mar 15;8(1). pii: E10. doi: 10.3390/jfb8010010 28294960

17. Sakai H, Sou K, Tsuchida E. Hemoglobin-vesicles as an artificial oxygen carrier. Methods Enzymol. 2009; 465: 363–384. doi: 10.1016/S0076-6879(09)65019-9 19913177

18. Shonaka T, Matsuno N, Obara H, Yoshikawa R, Nishikawa Y, Gouchi M, et al. Application of Perfusate With Human-Derived Oxygen Carrier Solution Under Subnormothermic Machine Perfusion for Donation After Cardiac Death Liver Grafts in Pigs. Transplant Proc. 2018; 50: 2821–2825. doi: 10.1016/j.transproceed.2018.02.184 30401404

19. Yoshikawa R, Obara H, Matsuno N, Morito N, Gouchi M, Otani M, et al. Ex Vivo Reperfusion Model to Evaluate Utility of Machine Preservation for Porcine Liver Donated After Cardiac Death. Transplant Proc. 2018; 50: 2826–2829. doi: 10.1016/j.transproceed.2018.04.020 30401405

20. Bochimoto H, Matsuno N, Ishihara Y, Shonaka T, Koga D, Hira Y, et al. The ultrastructural characteristics of porcine hepatocytes donated after cardiac death and preserved with warm machine perfusion preservation. PLoS One. 2017 Oct 12; 12(10):e0186352. doi: 10.1371/journal.pone.0186352 29023512

21. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 2013; 48: 452–458. doi: 10.1038/bmt.2012.244 23208313

22. Compagnon P, Levesque E, Hentati H, Disabato M, Calderaro J, Feray C, et al. An Oxygenated and Transportable Machine Perfusion System Fully Rescues Liver Grafts Exposed to Lethal Ischemic Damage in a Pig Model of DCD Liver Transplantation. Transplantation. 2017; 101(7): e205–e213. doi: 10.1097/TP.0000000000001764 28403128

23. Morito N, Obara H, Matsuno N, Enosawa S, Furukawa H. Oxygen consumption during hypothermic and subnormothermic machine perfusions of porcine liver grafts after cardiac death. J Artif Organs. 2018; 21: 450–457. doi: 10.1007/s10047-018-1063-0 30046934

24. Lüer B, Koetting M, Efferz P, Minor T. Role of oxygen during hypothermic machine perfusion preservation of the liver. Transpl Int. 2010; 23: 944–950. doi: 10.1111/j.1432-2277.2010.01067.x 20210932

25. Tolboom H, Izamis ML, Sharma N, Milwid JM, Uygun B, Berthiaume F, et al. Subnormothermic machine perfusion at both 20°C and 30°C recovers ischemic rat livers for successful transplantation. J Surg Res. 2012; 175:149–156. doi: 10.1016/j.jss.2011.03.003 21550058

26. Furukori M, Matsuno N, Meng LT, Shonaka T, Nishikawa Y, Imai K, et al. Subnormothermic Machine Perfusion Preservation With Rewarming for Donation After Cardiac Death Liver Grafts in Pigs. Transplant Proc. 2016; 48: 1239–1243. doi: 10.1016/j.transproceed.2015.12.076 27320595

27. Spetzler VN, Goldaracena N, Echiverri J, Kaths JM, Louis KS, Adeyi OA, et al. Subnormothermic ex vivo liver perfusion is a safe alternative to cold static storage for preserving standard criteria grafts. Liver Transpl. 2016; 22: 111–119. doi: 10.1002/lt.24340 26390093

28. Fontes P, Lopez R, van der Plaats A, Vodovotz Y, Minervini M, Scott V, et al. Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions. Am J Transplant. 2015; 15: 381–394. doi: 10.1111/ajt.12991 25612645

29. Patel MJ, Webb EJ, Shelbourn TE, Mattia-Goldberg C, George AJ, Zhang F, et al. Absence of immunogenicity of diaspirin cross-linked hemoglobin in humans. Blood. 1998; 91: 710–716. 9427730

30. Ueki S, Dhupar R, Cardinal J, Tsung A, Yoshida J, Ozaki KS, et al. Critical role of interferon regulatory factor-1 in murine liver transplant ischemia reperfusion injury. Hepatology. 2010; 51: 1692–1701. doi: 10.1002/hep.23501 20131404

31. Obara H, Matsuno N, Enosawa S, Shigeta T, Huai-Che H, Hirano T, et al. Pretransplant screening and evaluation of liver graft viability using machine perfusion preservation in porcine transplantation. Transplant Proc. 2012; 44: 959–961. doi: 10.1016/j.transproceed.2012.01.104 22564596

32. Liu Q, Nassar A, Farias K, Buccini L, Mangino MJ, Baldwin W, et al. Comparing Normothermic Machine Perfusion Preservation With Different Perfusates on Porcine Livers From Donors After Circulatory Death. Am J Transplant. 2016; 16: 794–807. doi: 10.1111/ajt.13546 26663737

33. Maione F, Gilbo N, Lazzaro S, Friend P, Camussi G, Romagnoli R et al. Porcine Isolated Liver Perfusion for the Study of Ischemia Reperfusion Injury: A Systematic Review. Transplantation. 2018;102:1039–1049. doi: 10.1097/TP.0000000000002156 29509572

34. Yoshikawa R, Matsuno N, Morito N, Gouchi M, Otani M, Takahashi H, et al. Evaluation Using an Isolated Reperfusion Model for Porcine Liver Donated After Cardiac Death Preserved with Oxygenated Hypothermic Machine Perfusion. Ann Transplant. 2018; 23: 822–827. doi: 10.12659/AOT.910008 30478252

35. Liu Q, Vekemans K, Iania L, Komuta M, Parkkinen J, Heedfeld V et al. Assessing warm ischemic injury of pig livers at hypothermic machine perfusion. J Surg Res. 2014;186:379–89. doi: 10.1016/j.jss.2013.07.034 24035230


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2019 Číslo 12