title: A new liver graft preparation method for uncontrolled non-heart-beating donors, combining short oxygenated warm perfusion and prostaglandin E1.
abstract: BACKGROUND
  To resolve the shortage of donors associated with liver transplantation, the potential uncontrolled non-heart-beating donor (UNHBD) pool is expected to increase. However, warm ischemia-reperfusion injury leads to inferior survival in transplantation using the grafts from UNHBD compared with those from heart-beating donors. To overcome this problem, we developed a new method for preparation of liver grafts from UNHBDs consisting of a combination of short oxygenated warm perfusion (SOWP) and prostaglandin E1 (PGE1).
  
  
  METHODS
  Using an ex vivo perfusion rat model, we examined the effectiveness of this new method.
  
  
  RESULTS
  Using SOWP and PGE1 treatment, the total amount of bile production during reperfusion in UNHBD grafts was increased to the same level as that in the heart-beating donor grafts. The addition of PGE1 to SOWP buffer decreased aspartate aminotransferase/alanine aminotransferase and tumor necrosis factor α levels during 1 h of reperfusion. Necrosis and apoptosis were significantly decreased by SOWP + PGE1 treatment. SOWP + PGE1 ameliorated induction of mitochondrial permeability transition, and the total amount of mitochondrial cytochrome c in the SOWP + PGE1 group after reperfusion was kept significantly higher than that in the no treatment group. Cytosolic c-Jun N-terminal protein kinase activation was significantly suppressed by SOWP + PGE1. Decrease in mitochondrial Bcl-2 was suppressed by SOWP alone and SOWP + PGE1 treatment, and Bax in the mitochondria was significantly suppressed by SOWP + PGE1.
  
  
  CONCLUSIONS
  SOWP and PGE1 prior to cold preservation significantly improved the function of liver grafts that underwent warm ischemia-reperfusion injury. Therefore, this method might be useful in liver transplantation using UNHBD grafts.
authors.affiliation: Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan. Electronic address: yasuhara@med.tohoku.ac.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Hara
authors.forename: Yorihiro
authors.initials: Y
authors.lastname: Akamatsu
authors.forename: Kai
authors.initials: K
authors.lastname: Maida
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kashiwadate
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
authors.forename: Susumu
authors.initials: S
authors.lastname: Satomi
mesh_terms: D000527:Alprostadil / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D023421:Models, Animal; D010100:Oxygen / Q000008:administration & dosage*; D010477:Perfusion / Q000379:methods*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D014019:Tissue Donors; D052096:Warm Ischemia / Q000379:methods*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000527:Alprostadil; D010100:Oxygen
keywords: Bcl-2 family; Cell death; Mitochondrial permeability transition; Uncontrolled non-heart-beating donors; Warm ischemia-reperfusion injury