title: Oxygenated Hypothermic Machine Perfusion After Static Cold Storage Improves Hepatobiliary Function of Extended Criteria Donor Livers.
abstract: BACKGROUND
  The mechanism through which oxygenated hypothermic machine perfusion (HMP) improves viability of human extended criteria donor (ECD) livers is not well known. Aim of this study was to examine the benefits of oxygenated HMP after static cold storage (SCS).
  
  
  METHODS
  Eighteen ECD livers that were declined for transplantation underwent ex situ viability testing using normothermic (37 °C) machine perfusion (NMP) after traditional SCS (0 °C-4 °C) for 7 to 9 hours. In the intervention group (n = 6), livers underwent 2 hours of oxygenated HMP (at 12 °C) after SCS and before NMP. Twelve control livers underwent NMP without oxygenated HMP after SCS.
  
  
  RESULTS
  During HMP, hepatic ATP content increased greater than 15-fold, and levels remained significantly higher during the first 4 hours of NMP in the HMP group, compared with controls. Cumulative bile production and biliary secretion of bilirubin and bicarbonate were significantly higher after HMP, compared with controls. In addition, the levels of lactate and glucose were less elevated after HMP compared with SCS preservation alone. In contrast, there were no differences in levels of hepatobiliary injury markers AST, ALT, LDH, and gamma-GT after 6 hours of NMP. Hepatic histology at baseline and after 6 hours of NMP revealed no differences in the amount of ischemic necrosis between both groups.
  
  
  CONCLUSIONS
  Two hours of oxygenated HMP after traditional SCS restores hepatic ATP levels and improves hepatobiliary function but does not reduce (preexisting) hepatobiliary injury in ECD livers.
authors: 1 Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 2 Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 3 Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Andrie C
authors: AC
authors: Westerkamp
authors: Negin
authors: N
authors: Karimian
authors: Alix P M
authors: AP
authors: Matton
authors: Paria
authors: P
authors: Mahboub
authors: Rianne
authors: R
authors: van Rijn
authors: Janneke
authors: J
authors: Wiersema-Buist
authors: Marieke T
authors: MT
authors: de Boer
authors: Henri G D
authors: HG
authors: Leuvenink
authors: Annette S H
authors: AS
authors: Gouw
authors: Ton
authors: T
authors: Lisman
authors: Robert J
authors: RJ
authors: Porte
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D001639:Bicarbonates / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D050377:Cold Ischemia / Q000009:adverse effects; D046148:Donor Selection; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D010100:Oxygen / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion / Q000379:methods*; D013997:Time Factors; D014019:Tissue Donors / Q000600:supply & distribution*; D014022:Tissue Survival
chemical_list: D001639:Bicarbonates; D015415:Biomarkers; D000255:Adenosine Triphosphate; D001663:Bilirubin; D010100:Oxygen