title: Recombinant human soluble thrombomodulin (ART-123) prevents warm ischemia-reperfusion injury in liver grafts from non-heart-beating donors.
abstract: BACKGROUND
  Liver transplantation is an established treatment for end-stage liver disease. However, an ongoing problem worldwide concerning this treatment is the shortage of grafts. Although transplantation using grafts from non-heart-beating donors (NHBDs) is considered a promising solution, some researchers have reported that these liver grafts are associated with primary graft nonfunction and biliary complications. The purpose of this study was to establish a safe technique procuring liver grafts from marginal donors such as NHBDs.
  
  
  METHODS
  Male Wistar rats were divided into three groups: (1) the heart-beating (HB) group, whose livers were retrieved from HB donors; (2) the non-HB (NHB) group, whose livers were retrieved from NHBDs that had experienced an apnea-induced agonal condition (for this group, livers were subjected to warm ischemia for 30 minutes after cardiac arrest); and (3) the recombinant human soluble thrombomodulin (ART-123) group, whose livers were retrieved in the same manner as the NHB group but pretreated with ART-123 (1 mg/kg) at the agonal stage. The livers were reperfused for 60 minutes with oxygenated Krebs-Henseleit bicarbonate buffer after cold preservation for 6 hours.
  
  
  RESULTS
  Bile production and portal flow volume in the ART-123 group were significantly higher than those in the NHB group. Alanine aminotransferase levels in the ART-123 group were significantly lower than those in the NHB group. Histological findings showed the narrowing of sinusoidal spaces and necroses in the NHB group were more severe than those in the ART-123 group.
  
  
  CONCLUSIONS
  These results suggest that thrombomodulin may improve the viability of liver grafts from NHBDs.
authors.affiliation: Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan. kashiwadate-nhn@umin.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Kashiwadate
authors.forename: S
authors.initials: S
authors.lastname: Miyagi
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
authors.forename: Y
authors.initials: Y
authors.lastname: Akamatsu
authors.forename: N
authors.initials: N
authors.lastname: Kawagishi
authors.forename: S
authors.initials: S
authors.lastname: Sekiguchi
authors.forename: S
authors.initials: S
authors.lastname: Satomi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001646:Bile / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008102:Liver Circulation / Q000187:drug effects; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D009336:Necrosis; D011169:Portal Vein / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015424:Reperfusion / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018180:Thrombomodulin; D013997:Time Factors; D014022:Tissue Survival / Q000187:drug effects; D052096:Warm Ischemia / Q000009:adverse effects*
chemical_list: C472045:ART123; D011994:Recombinant Proteins; D018180:Thrombomodulin; D000410:Alanine Transaminase