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Attempt to rescue discarded human liver grafts by end ischemic hypothermic oxygenated machine perfusion.

Abstract

In a porcine liver transplant model, a brief period of oxygenated hypothermic machine perfusion (HMP) at the end of simple cold storage (SCS) has been shown to improve the viability of damaged liver grafts. To test the clinical validity of this strategy, we randomized SCS-discarded human liver grafts to either 4 hours of HMP (n = 13) or an additional 4 hours of SCS (n = 14). All livers were then warm reperfused to mimic ischemia-reperfusion injury ex vivo. The settings for HMP were: portal vein: 3 mm Hg, 300 mL/min and hepatic artery: 20 mm Hg, pO(2): 300 mm Hg. Perfusion used Kidney Machine Perfusion Solution at 4°C to 8°C. During warm reperfusion, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) values were higher (P < .015) among the SCS versus HMP methods at all times. The AST slope was lower in HMP versus SCS (P = .01). The LDH slope tended to be lower for HMP versus SCS (P = .07). Morphological scores were not different between HMP and SCS. At the start of warm reperfusion, MAPK was lower in HMP versus SCS (P = .02). Endothelin-1 (EDN1) and ICAM-1 tended to be lower in HMP versus SCS (P = .1 and .07, respectively). No difference was noted in MAPK, EDN1, and ICAM-1 after 60 or 120 minutes of warm reperfusion. In conclusion, HMP down-regulated MAPK and tended to reduce EDN1 and ICAM-1 mRNA in human liver grafts. During warm reperfusion, HMP versus SCS livers showed reduced AST and LDH release but no morphological difference. Further optimization of liver HMP may require different timing/duration of perfusion and/or an higher perfusion temperature.

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  • Authors+Show Affiliations

    ,

    Departement gezondheidszorg en technologie, Katholieke Hogeschool Leuven, Catholic University of Leuven, Leuven, Belgium.

    , , , , , ,

    Source

    Transplantation proceedings 43:9 2011 Nov pg 3455-9

    MeSH

    Animals
    Biopsy
    Cold Ischemia
    Cold Temperature
    Gene Expression Regulation
    Graft Survival
    Humans
    Liver
    Liver Transplantation
    Organ Preservation
    Organ Preservation Solutions
    Oxygen
    Perfusion
    Reperfusion
    Risk
    Swine

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22099819

    Citation

    Vekemans, K, et al. "Attempt to Rescue Discarded Human Liver Grafts By End Ischemic Hypothermic Oxygenated Machine Perfusion." Transplantation Proceedings, vol. 43, no. 9, 2011, pp. 3455-9.
    Vekemans K, van Pelt J, Komuta M, et al. Attempt to rescue discarded human liver grafts by end ischemic hypothermic oxygenated machine perfusion. Transplant Proc. 2011;43(9):3455-9.
    Vekemans, K., van Pelt, J., Komuta, M., Wylin, T., Heedfeld, V., Detry, O., ... Pirenne, J. (2011). Attempt to rescue discarded human liver grafts by end ischemic hypothermic oxygenated machine perfusion. Transplantation Proceedings, 43(9), pp. 3455-9. doi:10.1016/j.transproceed.2011.09.029.
    Vekemans K, et al. Attempt to Rescue Discarded Human Liver Grafts By End Ischemic Hypothermic Oxygenated Machine Perfusion. Transplant Proc. 2011;43(9):3455-9. PubMed PMID: 22099819.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Attempt to rescue discarded human liver grafts by end ischemic hypothermic oxygenated machine perfusion. AU - Vekemans,K, AU - van Pelt,J, AU - Komuta,M, AU - Wylin,T, AU - Heedfeld,V, AU - Detry,O, AU - Monbaliu,D, AU - Pirenne,J, PY - 2011/11/22/entrez PY - 2011/11/22/pubmed PY - 2014/10/1/medline SP - 3455 EP - 9 JF - Transplantation proceedings JO - Transplant. Proc. VL - 43 IS - 9 N2 - In a porcine liver transplant model, a brief period of oxygenated hypothermic machine perfusion (HMP) at the end of simple cold storage (SCS) has been shown to improve the viability of damaged liver grafts. To test the clinical validity of this strategy, we randomized SCS-discarded human liver grafts to either 4 hours of HMP (n = 13) or an additional 4 hours of SCS (n = 14). All livers were then warm reperfused to mimic ischemia-reperfusion injury ex vivo. The settings for HMP were: portal vein: 3 mm Hg, 300 mL/min and hepatic artery: 20 mm Hg, pO(2): 300 mm Hg. Perfusion used Kidney Machine Perfusion Solution at 4°C to 8°C. During warm reperfusion, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) values were higher (P < .015) among the SCS versus HMP methods at all times. The AST slope was lower in HMP versus SCS (P = .01). The LDH slope tended to be lower for HMP versus SCS (P = .07). Morphological scores were not different between HMP and SCS. At the start of warm reperfusion, MAPK was lower in HMP versus SCS (P = .02). Endothelin-1 (EDN1) and ICAM-1 tended to be lower in HMP versus SCS (P = .1 and .07, respectively). No difference was noted in MAPK, EDN1, and ICAM-1 after 60 or 120 minutes of warm reperfusion. In conclusion, HMP down-regulated MAPK and tended to reduce EDN1 and ICAM-1 mRNA in human liver grafts. During warm reperfusion, HMP versus SCS livers showed reduced AST and LDH release but no morphological difference. Further optimization of liver HMP may require different timing/duration of perfusion and/or an higher perfusion temperature. SN - 1873-2623 UR - https://www.unboundmedicine.com/medline/citation/22099819/Attempt_to_rescue_discarded_human_liver_grafts_by_end_ischemic_hypothermic_oxygenated_machine_perfusion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-1345(11)01204-8 DB - PRIME DP - Unbound Medicine ER -