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Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death.

Abstract

BACKGROUND

Livers derived from donation after circulatory death (DCD) are increasingly accepted for transplantation. However, DCD livers suffer additional donor warm ischemia, leading to biliary injury and more biliary complications after transplantation. It is unknown whether oxygenated machine perfusion results in better preservation of biliary epithelium and the peribiliary vasculature. We compared oxygenated hypothermic machine perfusion (HMP) with static cold storage (SCS) in a porcine DCD model.

METHODS

After 30 min of cardiac arrest, livers were perfused in situ with HTK solution (4°C) and preserved for 4 h by either SCS (n = 9) or oxygenated HMP (10°C; n = 9), using pressure-controlled arterial and portal venous perfusion. To simulate transplantation, livers were reperfused ex vivo at 37°C with oxygenated autologous blood. Bile duct injury and function were determined by biochemical and molecular markers, and a systematic histological scoring system.

RESULTS

After reperfusion, arterial flow was higher in the HMP group, compared to SCS (251±28 vs 166±28 mL/min, respectively, after 1 hour of reperfusion; p = 0.003). Release of hepatocellular enzymes was significantly higher in the SCS group. Markers of biliary epithelial injury (biliary LDH, gamma-GT) and function (biliary pH and bicarbonate, and biliary transporter expression) were similar in the two groups. However, histology of bile ducts revealed significantly less arteriolonecrosis of the peribiliary vascular plexus in HMP preserved livers (>50% arteriolonecrosis was observed in 7 bile ducts of the SCS preserved livers versus only 1 bile duct of the HMP preserved livers; p = 0.024).

CONCLUSIONS

Oxygenated HMP prevents arteriolonecrosis of the peribiliary vascular plexus of the bile ducts of DCD pig livers and results in higher arterial flow after reperfusion. Together this may contribute to better perfusion of the bile ducts, providing a potential advantage in the post-ischemic recovery of bile ducts.

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  • Authors+Show Affiliations

    ,

    Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands ; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

    ,

    Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands ; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

    ,

    Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands ; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

    ,

    Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

    ,

    Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

    ,

    Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

    ,

    Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

    ,

    Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands ; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

    Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

    Source

    PloS one 9:2 2014 pg e88521

    MeSH

    Animals
    Arterioles
    Aspartate Aminotransferases
    Biliary Tract
    Death
    Epithelium
    Hepatocytes
    Hypothermia, Induced
    L-Lactate Dehydrogenase
    Liver
    Liver Transplantation
    Necrosis
    Nerve Fibers
    Organ Preservation
    Oxidative Stress
    Oxygen
    Perfusion
    Reperfusion
    Sus scrofa
    Tissue and Organ Procurement

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    24551114

    Citation

    Op den Dries, Sanna, et al. "Hypothermic Oxygenated Machine Perfusion Prevents Arteriolonecrosis of the Peribiliary Plexus in Pig Livers Donated After Circulatory Death." PloS One, vol. 9, no. 2, 2014, pp. e88521.
    Op den Dries S, Sutton ME, Karimian N, et al. Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death. PLoS ONE. 2014;9(2):e88521.
    Op den Dries, S., Sutton, M. E., Karimian, N., de Boer, M. T., Wiersema-Buist, J., Gouw, A. S., ... Porte, R. J. (2014). Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death. PloS One, 9(2), pp. e88521. doi:10.1371/journal.pone.0088521.
    Op den Dries S, et al. Hypothermic Oxygenated Machine Perfusion Prevents Arteriolonecrosis of the Peribiliary Plexus in Pig Livers Donated After Circulatory Death. PLoS ONE. 2014;9(2):e88521. PubMed PMID: 24551114.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death. AU - Op den Dries,Sanna, AU - Sutton,Michael E, AU - Karimian,Negin, AU - de Boer,Marieke T, AU - Wiersema-Buist,Janneke, AU - Gouw,Annette S H, AU - Leuvenink,Henri G D, AU - Lisman,Ton, AU - Porte,Robert J, Y1 - 2014/02/14/ PY - 2013/10/14/received PY - 2014/01/07/accepted PY - 2014/2/20/entrez PY - 2014/2/20/pubmed PY - 2014/10/22/medline SP - e88521 EP - e88521 JF - PloS one JO - PLoS ONE VL - 9 IS - 2 N2 - BACKGROUND: Livers derived from donation after circulatory death (DCD) are increasingly accepted for transplantation. However, DCD livers suffer additional donor warm ischemia, leading to biliary injury and more biliary complications after transplantation. It is unknown whether oxygenated machine perfusion results in better preservation of biliary epithelium and the peribiliary vasculature. We compared oxygenated hypothermic machine perfusion (HMP) with static cold storage (SCS) in a porcine DCD model. METHODS: After 30 min of cardiac arrest, livers were perfused in situ with HTK solution (4°C) and preserved for 4 h by either SCS (n = 9) or oxygenated HMP (10°C; n = 9), using pressure-controlled arterial and portal venous perfusion. To simulate transplantation, livers were reperfused ex vivo at 37°C with oxygenated autologous blood. Bile duct injury and function were determined by biochemical and molecular markers, and a systematic histological scoring system. RESULTS: After reperfusion, arterial flow was higher in the HMP group, compared to SCS (251±28 vs 166±28 mL/min, respectively, after 1 hour of reperfusion; p = 0.003). Release of hepatocellular enzymes was significantly higher in the SCS group. Markers of biliary epithelial injury (biliary LDH, gamma-GT) and function (biliary pH and bicarbonate, and biliary transporter expression) were similar in the two groups. However, histology of bile ducts revealed significantly less arteriolonecrosis of the peribiliary vascular plexus in HMP preserved livers (>50% arteriolonecrosis was observed in 7 bile ducts of the SCS preserved livers versus only 1 bile duct of the HMP preserved livers; p = 0.024). CONCLUSIONS: Oxygenated HMP prevents arteriolonecrosis of the peribiliary vascular plexus of the bile ducts of DCD pig livers and results in higher arterial flow after reperfusion. Together this may contribute to better perfusion of the bile ducts, providing a potential advantage in the post-ischemic recovery of bile ducts. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24551114/Hypothermic_oxygenated_machine_perfusion_prevents_arteriolonecrosis_of_the_peribiliary_plexus_in_pig_livers_donated_after_circulatory_death_ L2 - http://dx.plos.org/10.1371/journal.pone.0088521 DB - PRIME DP - Unbound Medicine ER -