title: Fate of hepatocyte and sinusoidal lining cell function and kinetics after extended cold preservation and transplantation of the rat liver.
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.
authors.affiliation: First Department of Surgery, School of Medicine, Shinshu University, Matsumoto, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Miyagawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imamura
authors.forename: Junpei
authors.initials: J
authors.lastname: Soeda
authors.forename: Kotaro
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mochida
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsuyama
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawasaki
mesh_terms: D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001646:Bile / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D005978:Glutathione; D006085:Graft Survival; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D007328:Insulin; D019394:Ki-67 Antigen / Q000032:analysis; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000502:physiology; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology*; D009336:Necrosis; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D011887:Raffinose; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014185:Transplantation, Isogeneic
chemical_list: D007328:Insulin; D019394:Ki-67 Antigen; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose