#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The impact on the bioenergetic status and oxidative-mediated tissue injury of a combined protocol of hypothermic and normothermic machine perfusion using an acellular haemoglobin-based oxygen carrier: The cold-to-warm machine perfusion of the liver


Autoři: Yuri L. Boteon aff001;  Richard W. Laing aff002;  Andrea Schlegel aff001;  Lorraine Wallace aff002;  Amanda Smith aff001;  Joseph Attard aff001;  Ricky H. Bhogal aff002;  Gary Reynolds aff002;  M. Thamara PR Perera aff001;  Paolo Muiesan aff001;  Darius F. Mirza aff001;  Hynek Mergental aff001;  Simon C. Afford aff002
Působiště autorů: Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom aff001;  Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom aff002;  National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224066

Souhrn

Introduction

The combination of hypothermic and normothermic machine perfusion (HMP+NMP) of the liver provides individual benefits of both techniques, improving the rescue of marginal organs. The aim of this study was to investigate the effect on the bioenergetic status and the oxidative-mediated tissue injury of an uninterrupted combined protocol of HMP+NMP using a single haemoglobin-based oxygen carrier (HBOC)-based perfusate.

Methods

Ten discarded human donor livers had either 2 hours of dual hypothermic oxygenated perfusion (D-HOPE) with sequential controlled rewarming (COR) and then NMP using the HBOC-based perfusate uninterruptedly (cold-to-warm group); or 2 hours of hypothermic oxygenated perfusion (HOPE) with an oxygen carrier-free perfusate, followed by perfusate exchange and then NMP with an HBOC-based perfusate. Markers of liver function, tissue adenosine triphosphate (ATP) levels and tissue injury were systematically assessed.

Results

The hypothermic phase downregulated mitochondrial respiration and increased ATP levels in both groups. The cold-to-warm group presented higher arterial vascular resistance during rewarming/NMP (p = 0.03) with a trend of lower arterial flow (p = 0.09). At the end of NMP tissue expression of markers of reactive oxygen species production, oxidative injury and inflammation were comparable between the groups.

Conclusion

The uninterrupted combined protocol of HMP+NMP using an HBOC-based perfusate—cold-to-warm MP—mitigated the oxidative-mediated tissue injury and enhanced hepatic energy stores, similarly to an interrupted combined protocol; however, it simplified the logistics of this combination and may favour its clinical applicability.

Klíčová slova:

Bile – Fatty liver – Inflammation – Liver – Liver transplantation – Mitochondria – Oxygen – Macrovesicular steatosis


Zdroje

1. Boteon YL, Afford SC, Mergental H. Pushing the limits: Machine preservation of the liver as a tool to recondition high-risk grafts. Current transplantation reports. 2018;5(2):113–20. Epub 2018/05/19. doi: 10.1007/s40472-018-0188-7 29774176.

2. Nasralla D, Coussios C, Mergental H, Akhtar MZ, Butler AJ, Ceresa CDL, et al. A randomized trial of normothermic preservation in liver transplantation. Nature. 2018;557(7703):50–6. Epub 2018/04/01. doi: 10.1038/s41586-018-0047-9 29670285.

3. Dutkowski P, Polak WG, Muiesan P, Schlegel A, Verhoeven CJ, Scalera I, et al. First comparison of Hypothermic Oxygenated PErfusion versus static cold storage of human donation after cardiac death liver transplants: An international-matched case analysis. Annals of surgery. 2015;262(5):764–71. Epub 2015/11/20. doi: 10.1097/SLA.0000000000001473 26583664.

4. Dutkowski P, Schlegel A, de Oliveira M, Mullhaupt B, Neff F, Clavien PA. HOPE for human liver grafts obtained from donors after cardiac death. Journal of hepatology. 2014;60(4):765–72. Epub 2013/12/04. doi: 10.1016/j.jhep.2013.11.023 24295869.

5. van Rijn R, Karimian N, Matton APM, Burlage LC, Westerkamp AC, van den Berg AP, et al. Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death. The British journal of surgery. 2017;104(7):907–17. Epub 2017/04/11. doi: 10.1002/bjs.10515 28394402.

6. Watson CJE, Jochmans I. From "Gut Feeling" to objectivity: Machine preservation of the liver as a tool to assess organ viability. Current transplantation reports. 2018;5(1):72–81. Epub 2018/03/23. doi: 10.1007/s40472-018-0178-9 29564205.

7. 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. The Journal of surgical research. 2014;186(1):379–89. Epub 2013/09/17. doi: 10.1016/j.jss.2013.07.034 24035230.

8. Boteon YL, Laing RW, Schlegel A, Wallace L, Smith A, Attard J, et al. Combined hypothermic and normothermic machine perfusion improves functional recovery of extended criteria donor livers. Liver transplantation. 2018;24(12):1699–715. Epub 2018/12/04. doi: 10.1002/lt.25315 30058119.

9. de Vries Y, Matton APM, Nijsten MWN, Werner MJM, van den Berg AP, de Boer MT, et al. Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution. American journal of transplantation. 2019;19(4):1202–11. Epub 2019/01/23. doi: 10.1111/ajt.15228 30588774.

10. Westerkamp AC, Karimian N, Matton AP, Mahboub P, van Rijn R, Wiersema-Buist J, et al. Oxygenated hypothermic machine perfusion after static cold storage improves hepatobiliary function of extended criteria donor livers. Transplantation. 2016;100(4):825–35. Epub 2016/02/11. doi: 10.1097/TP.0000000000001081 26863473.

11. van Leeuwen OB, de Vries Y, Fujiyoshi M, Nijsten MWN, Ubbink R, Pelgrim GJ, et al. Transplantation of high-risk donor livers after ex situ resuscitation and assessment using combined hypo- and normothermic machine perfusion: A prospective clinical trial. Annals of surgery. 2019. Epub 2019/08/16. doi: 10.1097/sla.0000000000003540 31415002.

12. Grossman R, Lewis FJ. The effect of cooling and low molecular weight dextran on blood sludging. The Journal of surgical research. 1964;4:360–2. Epub 1964/08/01. doi: 10.1016/s0022-4804(64)80084-6 14200439.

13. 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. American journal of transplantation. 2015;15(2):381–94. Epub 2015/01/22. doi: 10.1111/ajt.12991 25612645.

14. Laing RW, Bhogal RH, Wallace L, Boteon Y, Neil DAH, Smith A, et al. The use of an acellular oxygen carrier in a human liver model of normothermic machine perfusion. Transplantation. 2017; 101(11):2746–56. Epub 2017/05/19. doi: 10.1097/TP.0000000000001821 28520579.

15. Hoyer DP, Mathe Z, Gallinat A, Canbay AC, Treckmann JW, Rauen U, et al. Controlled oxygenated rewarming of cold stored livers prior to transplantation: First clinical application of a new concept. Transplantation. 2016;100(1):147–52. Epub 2016/01/04. doi: 10.1097/TP.0000000000000915 26479280.

16. Schopp I, Reissberg E, Luer B, Efferz P, Minor T. Controlled rewarming after hypothermia: adding a new principle to renal preservation. Clinical and translational science. 2015;8(5):475–8. Epub 2015/06/09. doi: 10.1111/cts.12295 26053383.

17. Oniscu GC. Liver Retrieval and Bench Surgery. Abdominal Organ Retrieval and Transplantation Bench Surgery: John Wiley & Sons; 2013. p. 73–90.

18. Sutton ME, op den Dries S, Karimian N, Weeder PD, de Boer MT, Wiersema-Buist J, et al. Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion. PloS one. 2014;9(11):e110642. Epub 2014/11/05. doi: 10.1371/journal.pone.0110642 25369327.

19. Mergental H, Perera MT, Laing RW, Muiesan P, Isaac JR, Smith A, et al. Transplantation of declined liver allografts following normothermic ex-situ evaluation. American journal of transplantation. 2016;16(11):3235–45. Epub 2016/10/28. doi: 10.1111/ajt.13875 27192971.

20. Laing RW, Mergental H, Yap C, Kirkham A, Whilku M, Barton D, et al. Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial. BMJ open. 2017;7(11):e017733. Epub 2017/12/01. 29183928.

21. Ninomiya M, Shirabe K, Shimada M, Terashi T, Maehara Y. Role of UCP2 expression after hepatic warm ischemia-reperfusion in the rat. Gut Liver. 2011;5(4):486–92. Epub 2011/11/21. doi: 10.5009/gnl.2011.5.4.486 22195248.

22. Kato Y, Tanaka J, Koyama K. Intralobular heterogeneity of oxidative stress and cell death in ischemia-reperfused rat liver. The Journal of surgical research. 2001;95(2):99–106. Epub 2001/02/01. doi: 10.1006/jsre.2000.5831 11162032.

23. Echtay KS, Murphy MP, Smith RA, Talbot DA, Brand MD. Superoxide activates mitochondrial uncoupling protein 2 from the matrix side. Studies using targeted antioxidants. The journal of biological chemistry. 2002;277(49):47129–35. Epub 2002/10/10. doi: 10.1074/jbc.M208262200 12372827.

24. Wu H-S, Zhang J-X, Wang L, Tian Y, Wang H, Rotstein O. Toll-like receptor 4 involvement in hepatic ischemia/reperfusion injury in mice. Hepatobiliary & Pancreatic Diseases International. 2004;3(2):250–3. 15138120.

25. Tsung A, Sahai R, Tanaka H, Nakao A, Fink MP, Lotze MT, et al. The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. The Journal of experimental medicine. 2005;201(7):1135–43. Epub 2005/03/28. doi: 10.1084/jem.20042614 15795240.

26. Luan X, Liu Y, Li M. The role of CD14 and Toll-Like Receptor 4 of Kupffer Cells in hepatic ischemia-reperfusion injury in rats. Transplantation proceedings. 2012;44(4):937–41. Epub 2012/05/05. doi: 10.1016/j.transproceed.2011.11.001 22564590

27. Kobayashi A, Imamura H, Isobe M, Matsuyama Y, Soeda J, Matsunaga K, et al. Mac-1 (CD11b/CD18) and intercellular adhesion molecule-1 in ischemia-reperfusion injury of rat liver. American journal of physiology gastrointestinal and liver physiology. 2001;281(2):G577–85. Epub 2001/07/12. doi: 10.1152/ajpgi.2001.281.2.G577 11447039.

28. Gordon S, Plüddemann A, Martinez Estrada F. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunological reviews. 2014;262(1):36–55. Epub 2014/10/15. doi: 10.1111/imr.12223 25319326.

29. Kaemmerer D, Peter L, Lupp A, Schulz S, Sanger J, Baum RP, et al. Comparing of IRS and Her2 as immunohistochemical scoring schemes in gastroenteropancreatic neuroendocrine tumors. International journal of clinical and experimental pathology. 2012;5(3):187–94. Epub 2012/05/05. 22558472.

30. Schlegel A, Muller X, Dutkowski P. Hypothermic machine preservation of the liver: State of the art. Current transplantation reports. 2018;5(1):93–102. Epub 2018/03/23. doi: 10.1007/s40472-018-0183-z 29564206.

31. Liu Q, Vekemans K, van Pelt J, Pirenne J, Himmelreich U, Heedfeld V, et al. Discriminate liver warm ischemic injury during hypothermic machine perfusion by proton magnetic resonance spectroscopy: a study in a porcine model. Transplantation proceedings. 2009;41(8):3383–6. Epub 2009/10/28. doi: 10.1016/j.transproceed.2009.09.025 19857754.

32. Lazeyras F, Buhler L, Vallee JP, Hergt M, Nastasi A, Ruttimann R, et al. Detection of ATP by "in line" 31P magnetic resonance spectroscopy during oxygenated hypothermic pulsatile perfusion of pigs’ kidneys. Magma (New York, NY). 2012;25(5):391–9. Epub 2012/05/31. doi: 10.1007/s10334-012-0319-6 22644411.

33. Stowell CP. What happened to blood substitutes? Transfusion clinique et biologique: journal de la Societe francaise de transfusion sanguine. 2005;12(5):374–9. Epub 2005/12/06. doi: 10.1016/j.tracli.2005.10.002 16326128.

34. Liao JC, Hein TW, Vaughn MW, Huang KT, Kuo L. Intravascular flow decreases erythrocyte consumption of nitric oxide. Proceedings of the national academy of sciences of the United States of America. 1999;96(15):8757–61. Epub 1999/07/21. doi: 10.1073/pnas.96.15.8757 10411948.

35. Rioux F, Drapeau G, Marceau F. Recombinant human hemoglobin (rHb1.1) selectively inhibits vasorelaxation elicited by nitric oxide donors in rabbit isolated aortic rings. Journal of cardiovascular pharmacology. 1995;25(4):587–94. Epub 1995/04/01. doi: 10.1097/00005344-199504000-00012 7596127.

36. Cabrales P, Intaglietta M, Tsai AG. Increase plasma viscosity sustains microcirculation after resuscitation from hemorrhagic shock and continuous bleeding. Shock. 2005;23(6):549–55. Epub 2005/05/18. 15897809.

37. Cabrales P, Tsai AG, Intaglietta M. Hyperosmotic-hyperoncotic versus hyperosmotic-hyperviscous: small volume resuscitation in hemorrhagic shock. Shock. 2004;22(5):431–7. Epub 2004/10/19. doi: 10.1097/01.shk.0000140662.72907.95 15489635.

38. de Wit C, Schafer C, von Bismarck P, Bolz SS, Pohl U. Elevation of plasma viscosity induces sustained NO-mediated dilation in the hamster cremaster microcirculation in vivo. Pflugers Archiv: European journal of physiology. 1997;434(4):354–61. Epub 1997/08/01. doi: 10.1007/s004240050408 9211800.

39. Tsai AG, Vandegriff KD, Intaglietta M, Winslow RM. Targeted O2 delivery by low-P50 hemoglobin: a new basis for O2 therapeutics. American journal of physiology Heart and circulatory physiology. 2003;285(4):H1411–9. Epub 2003/06/14. doi: 10.1152/ajpheart.00307.2003 12805024.

40. Cabrales P, Tsai AG, Winslow RM, Intaglietta M. Effects of extreme hemodilution with hemoglobin-based O2 carriers on microvascular pressure. American journal of physiology Heart and circulatory physiology. 2005;288(5):H2146–53. Epub 2005/01/08. doi: 10.1152/ajpheart.00749.2004 15637119.

41. Hughes GS Jr., Antal EJ, Locker PK, Francom SF, Adams WJ, Jacobs EE Jr. Physiology and pharmacokinetics of a novel hemoglobin-based oxygen carrier in humans. Critical care medicine. 1996;24(5):756–64. Epub 1996/05/01. doi: 10.1097/00003246-199605000-00006 8706450.

42. Sprung J, Kindscher JD, Wahr JA, Levy JH, Monk TG, Moritz MW, et al. The use of bovine hemoglobin glutamer-250 (Hemopure) in surgical patients: results of a multicenter, randomized, single-blinded trial. Anesthesia and analgesia. 2002;94(4):799–808. Epub 2002/03/28. doi: 10.1097/00000539-200204000-00006 11916776.

43. Johnson D. Perioperative methemoglobinemia. Canadian journal of anaesthesia. 2005;52(7):665–8. Epub 2005/08/17. doi: 10.1007/BF03016550 16103376.

44. Chui JS, Poon WT, Chan KC, Chan AY, Buckley TA. Nitrite-induced methaemoglobinaemia—aetiology, diagnosis and treatment. Anaesthesia. 2005;60(5):496–500. Epub 2005/04/12. doi: 10.1111/j.1365-2044.2004.04076.x 15819771.

45. Watson CJE, Kosmoliaptsis V, Pley C, Randle L, Fear C, Crick K, et al. Observations on the ex situ perfusion of livers for transplantation. American journal of transplantation. 2018;18(8):2005–20. Epub 2018/02/09. doi: 10.1111/ajt.14687 29419931.

46. Matton APM, de Vries Y, Burlage LC, van Rijn R, Fujiyoshi M, de Meijer VE, et al. Biliary bicarbonate, pH and glucose are suitable biomarkers of biliary viability during ex situ normothermic machine perfusion of human donor livers. Transplantation. 2019 Jul;103(7):1405–13. Epub 2019/06/26. doi: 10.1097/TP.0000000000002500 30395120.


Článek vyšel v časopise

PLOS One


2019 Číslo 10
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Svět praktické medicíny 3/2024 (znalostní test z časopisu)
nový kurz

Kardiologické projevy hypereozinofilií
Autoři: prof. MUDr. Petr Němec, Ph.D.

Střevní příprava před kolonoskopií
Autoři: MUDr. Klára Kmochová, Ph.D.

Aktuální možnosti diagnostiky a léčby litiáz
Autoři: MUDr. Tomáš Ürge, PhD.

Závislosti moderní doby – digitální závislosti a hypnotika
Autoři: MUDr. Vladimír Kmoch

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#