Fate of hepatocyte and sinusoidal lining cell function and kinetics after extended cold preservation and transplantation of the rat liver

Liver Transpl. 2002 Apr;8(4):370-81. doi: 10.1053/jlts.2002.32281.

Abstract

We investigated the chronological profile of graft damage and recovery after liver cold ischemia-reperfusion (I/R) injury, with particular attention to the role of apoptosis on hepatocyte and sinusoidal endothelial cell (SEC) damage. Male Lewis rats underwent rearterialized orthotopic liver transplantation using grafts subjected to a short (University of Wisconsin [UW] solution for 1 hour [UW1h]) and prolonged period (UW16h) of cold preservation. Experiments were performed immediately after preservation and 4 hours, 24 hours, 3 days, and 7 days after reperfusion. At each time, graft function, incidence of apoptotic cells, expression of the epitope recognized by a monoclonal antibody specific to rat SECs (SE-1), and incidence of proliferating cells were estimated. In the UW16h group, the proportion of apoptotic SECs was markedly elevated at 4 hours. The incidence of hepatocyte apoptosis was very low, although massive hepatocyte necrosis was evident at 24 hours. The incidence of proliferating hepatocytes and SECs peaked at 3 days, then returned to normal by 7 days. SE-1 expression was reduced immediately after preservation, followed by a marked reduction at 4 and 24 hours after reperfusion, and expression returned to normal by 7 days. Although SEC apoptosis was induced in the early phase of cold I/R injury, hepatocyte damage developed without the occurrence of apoptosis. Regeneration of both hepatocytes and SECs after cold I/R injury peaked at 3 days and was complete by 7 days, whereas functional recovery of these cell populations was complete 3 days after reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine
  • Allopurinol
  • Animals
  • Apoptosis / physiology
  • Bile / metabolism
  • Caspase 3
  • Caspases / metabolism
  • Cell Division / physiology
  • Glutathione
  • Graft Survival
  • Hepatocytes / cytology
  • Hepatocytes / physiology*
  • Immunohistochemistry
  • Insulin
  • Ki-67 Antigen / analysis
  • Kinetics
  • Liver Function Tests
  • Liver Transplantation / pathology
  • Liver Transplantation / physiology*
  • Liver* / cytology
  • Liver* / physiology
  • Necrosis
  • Organ Preservation / methods*
  • Organ Preservation Solutions
  • Raffinose
  • Rats
  • Rats, Inbred Lew
  • Time Factors
  • Transplantation, Isogeneic

Substances

  • Insulin
  • Ki-67 Antigen
  • Organ Preservation Solutions
  • University of Wisconsin-lactobionate solution
  • Allopurinol
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Glutathione
  • Adenosine
  • Raffinose