title: End-ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature.
abstract: A short period of oxygenated machine perfusion (MP) after static cold storage (SCS) may reduce biliary injury in donation after cardiac death (DCD) donor livers. However, the ideal perfusion temperature for protection of the bile ducts is unknown. In this study, the optimal perfusion temperature for protection of the bile ducts was assessed. DCD rat livers were preserved by SCS for 6 hours. Thereafter, 1 hour of oxygenated MP was performed using either hypothermic machine perfusion, subnormothermic machine perfusion, or with controlled oxygenated rewarming (COR) conditions. Subsequently, graft and bile duct viability were assessed during 2 hours of normothermic ex situ reperfusion. In the MP study groups, lower levels of transaminases, lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances were measured compared to SCS. In parallel, mitochondrial oxygen consumption and adenosine triphosphate (ATP) production were significantly higher in the MP groups. Biomarkers of biliary function, including bile production, biliary bicarbonate concentration, and pH, were significantly higher in the MP groups, whereas biomarkers of biliary epithelial injury (biliary gamma-glutamyltransferase [GGT] and LDH), were significantly lower in MP preserved livers. Histological analysis revealed less injury of large bile duct epithelium in the MP groups compared to SCS. In conclusion, compared to SCS, end-ischemic oxygenated MP of DCD livers provides better preservation of biliary epithelial function and morphology, independent of the temperature at which MP is performed. End-ischemic oxygenated MP could reduce biliary injury after DCD liver transplantation.
authors.affiliation: Surgical Research Laboratory.|Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery.
authors.forename: Andrie C
authors.initials: AC
authors.lastname: Westerkamp
authors.affiliation: Surgical Research Laboratory.
authors.forename: Paria
authors.initials: P
authors.lastname: Mahboub
authors.affiliation: Surgical Research Laboratory.|Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery.
authors.forename: Sophie L
authors.initials: SL
authors.lastname: Meyer
authors.affiliation: Departments of Cardiothoracic Surgery.
authors.forename: Maximilia
authors.initials: M
authors.lastname: Hottenrott
authors.affiliation: Surgical Research Laboratory.
authors.forename: Petra J
authors.initials: PJ
authors.lastname: Ottens
authors.affiliation: Surgical Research Laboratory.
authors.forename: Janneke
authors.initials: J
authors.lastname: Wiersema-Buist
authors.affiliation: Departments of Pathology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Annette S H
authors.initials: AS
authors.lastname: Gouw
authors.affiliation: Surgical Research Laboratory.|Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery.
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
authors.affiliation: Surgical Research Laboratory.
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Porte
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001649:Bile Duct Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001652:Bile Ducts / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D050377:Cold Ischemia / Q000009:adverse effects; D004734:Energy Metabolism; D006498:Hepatectomy; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage* / Q000378:metabolism; D010101:Oxygen Consumption; D010477:Perfusion / Q000009:adverse effects / Q000379:methods*; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013696:Temperature; D013997:Time Factors; D052096:Warm Ischemia / Q000009:adverse effects
chemical_list: D015415:Biomarkers; D000255:Adenosine Triphosphate; D010100:Oxygen