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Normothermic machine perfusion (NMP) shows promise for liver transplantation, but prolonged cold ischemic time (CIT) before NMP can still lead to hepatocellular injury and apoptosis, requiring further study.

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Area of Science:

  • Transplantation immunology
  • Organ preservation
  • Hepatology

Background:

  • Prolonged cold ischemic time (CIT) in static cold storage is linked to liver transplant complications.
  • Normothermic machine perfusion (NMP) reduces early allograft dysfunction and biliary issues.
  • The efficacy of NMP in rehabilitating organs with extended CIT is not well understood.

Purpose of the Study:

  • To investigate the impact of prolonged cold ischemic time (CIT) on liver grafts undergoing normothermic machine perfusion (NMP).
  • To assess the potential of NMP to repair organs subjected to extended ischemia-reperfusion injury.

Main Methods:

  • Pig livers underwent static cold storage for 2, 24, or 48 hours (CIT) before ex situ NMP.
  • Evaluated liver appearance, perfusion parameters, perfusate biomarkers (lactate, AST, ALT), bile production, and histology (H&E, caspase-3).

Main Results:

  • Extended CIT livers showed visual heterogeneity and elevated perfusate lactate that persisted.
  • While long CIT livers had temporary lactate reduction, they exhibited hepatocellular injury (higher AST/ALT) and increased apoptosis (caspase-3 positive cells).

Conclusions:

  • NMP demonstrates potential benefits in liver transplantation.
  • Further research is needed to evaluate NMP's role in back-to-base models with prolonged CIT to fully understand ischemia-reperfusion injury impacts.