title: Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers.
abstract: Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD.
authors.affiliation: 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.
authors.forename: Sanna
authors.initials: S
authors.lastname: Op den Dries
authors.affiliation: 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.
authors.forename: Negin
authors.initials: N
authors.lastname: Karimian
authors.affiliation: 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.
authors.forename: Andrie C
authors.initials: AC
authors.lastname: Westerkamp
authors.affiliation: 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.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Sutton
authors.affiliation: 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.
authors.forename: Michiel
authors.initials: M
authors.lastname: Kuipers
authors.affiliation: Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Wiersema-Buist
authors.affiliation: Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Petra J
authors.initials: PJ
authors.lastname: Ottens
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Kuipers
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Ben N
authors.initials: BN
authors.lastname: Giepmans
authors.affiliation: Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
authors.affiliation: 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.
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Porte
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000166:cytology / Q000473:pathology* / Q000648:ultrastructure; D015415:Biomarkers / Q000097:blood; D050377:Cold Ischemia / Q000009:adverse effects; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D009926:Organ Preservation / Q000295:instrumentation / Q000379:methods*; D010477:Perfusion / Q000295:instrumentation / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew; D015424:Reperfusion / Q000009:adverse effects; D015427:Reperfusion Injury / Q000517:prevention & control*; D013696:Temperature; D020858:Tissue and Organ Harvesting / Q000009:adverse effects; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015415:Biomarkers; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase