title: 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.
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: 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: 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.
authors.forename: Marieke T
authors.initials: MT
authors.lastname: de Boer
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: Department 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, 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; D001160:Arterioles / Q000187:drug effects / Q000473:pathology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001659:Biliary Tract / Q000098:blood supply / Q000187:drug effects / Q000294:innervation*; D003643:Death; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D007036:Hypothermia, Induced; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D016031:Liver Transplantation; D009336:Necrosis; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology*; D009926:Organ Preservation; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology*; D010477:Perfusion; D015424:Reperfusion; D034421:Sus scrofa; D009927:Tissue and Organ Procurement
chemical_list: D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D010100:Oxygen