title: Oxygenated hypothermic machine perfusion after static cold storage improves endothelial function of extended criteria donor livers.
abstract: Lack of oxygen and biomechanical stimulation during static cold storage (SCS) of donor livers compromises endothelial cell function. We investigated the effect of end-ischemic oxygenated hypothermic machine perfusion (HMP) on endothelial cell function of extended criteria donor (ECD) livers.
  
  
  
  Eighteen livers, declined for transplantation, were transported to our center using static cold storage (SCS). After SCS, 6 livers underwent two hours of HMP, and subsequent normothermic machine perfusion (NMP) to assess viability. Twelve control livers underwent NMP immediately after SCS. mRNA expression of transcription factor Krüppel-like-factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) was quantified by RT-PCR. Endothelial cell function and injury were assessed by nitric oxide (NO) production and release of TM into the perfusate.
  
  
  
  In HMP livers, mRNA expression of KLF2 (p = 0.043), eNOS (p = 0.028), and TM (p = 0.028) increased significantly during NMP. In parallel, NO levels increased during NMP in HMP livers but not in controls. At the end of NMP cumulative TM release was significantly lower HMP livers, compared to controls (p = 0.028).
  
  
  
  A short period of two hours oxygenated HMP restores endothelial cell viability after SCS and subsequent normothermic reoxygenation of ECD livers.
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands; Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Burlage
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands; Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Negin
authors.initials: N
authors.lastname: Karimian
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands; Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Andrie C
authors.initials: AC
authors.lastname: Westerkamp
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Nienke
authors.initials: N
authors.lastname: Visser
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands; Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Alix P M
authors.initials: APM
authors.lastname: Matton
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands; Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Rianne
authors.initials: R
authors.lastname: van Rijn
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Jelle
authors.initials: J
authors.lastname: Adelmeijer
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center 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, The Netherlands.
authors.forename: Annette S H
authors.initials: ASH
authors.lastname: Gouw
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center 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, The Netherlands. Electronic address: r.j.porte@umcg.nl.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Porte
mesh_terms: D000368:Aged; D002470:Cell Survival; D003080:Cold Temperature; D046148:Donor Selection; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006498:Hepatectomy / Q000009:adverse effects; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009926:Organ Preservation / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D010100:Oxygen / Q000378:metabolism*; D010477:Perfusion / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018180:Thrombomodulin / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014019:Tissue Donors / Q000600:supply & distribution*
chemical_list: C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; C546931:THBD protein, human; D018180:Thrombomodulin; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen