Oxygenated hypothermic machine perfusion after static cold storage improves endothelial function of extended criteria donor livers

HPB (Oxford). 2017 Jun;19(6):538-546. doi: 10.1016/j.hpb.2017.02.439. Epub 2017 Mar 25.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: A short period of two hours oxygenated HMP restores endothelial cell viability after SCS and subsequent normothermic reoxygenation of ECD livers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Survival
  • Cold Temperature*
  • Donor Selection
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Female
  • Gene Expression Regulation
  • Hepatectomy* / adverse effects
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Liver / metabolism
  • Liver / pathology
  • Liver / surgery*
  • Liver Transplantation / adverse effects
  • Liver Transplantation / methods*
  • Male
  • Middle Aged
  • Netherlands
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • Organ Preservation / adverse effects
  • Organ Preservation / instrumentation
  • Organ Preservation / methods*
  • Oxygen / metabolism*
  • Perfusion / adverse effects
  • Perfusion / instrumentation
  • Perfusion / methods*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Thrombomodulin / genetics
  • Thrombomodulin / metabolism
  • Time Factors
  • Tissue Donors / supply & distribution*

Substances

  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • RNA, Messenger
  • THBD protein, human
  • Thrombomodulin
  • Nitric Oxide
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Oxygen