title: Pharmacologic graft protection without donor pretreatment in liver transplantation from non-heart-beating donors.
abstract: BACKGROUND
  Non-heart-beating donors (NHBDs) are considered potential sources of transplant organs in an effort to alleviate the problem of donor shortage in clinical liver transplantation. We investigated the possibility of pharmacologic protection of hepatic allograft function from NHBDs without donor pretreatment.
  
  
  METHODS
  Orthotopic liver transplantation was performed using pigs. In donors, cardiac arrest was induced by stopping the respirator. Forty-five minutes after cessation of the respirator, the liver was flushed with cold lactated Ringer's solution including heparin and with the University of Wisconsin (UW) solution, and then preserved for 8 hr at 4 degrees C in the UW solution. The pigs were divided into two groups: a control group and a treated group. In the treated group, an endothelin antagonist TAK-044 was added to the UW solutions (10 mg/L), and TAK-044 (10 mg/kg body weight) and a platelet activating factor antagonist E5880 (0.3 mg/kg body weight) were also administered to the recipients.
  
  
  RESULTS
  TAK-044 and E5880 treatment significantly increased the 7-day survival rate of the recipients (100% vs. 17%, P<0.05). In the treated group, portal venous pressure immediately after reperfusion of the graft was significantly lower than in the control group, and postoperative increase in serum concentrations of glutamic oxaloacetic transaminase and total bilirubin was attenuated. Moreover, the energy charge and adenosine triphosphate concentration of the liver were rapidly restored after reperfusion.
  
  
  CONCLUSIONS
  Pharmacologic modulation with TAK-044 and E5880 avoiding donor pretreatment can improve the viability of hepatic allografts procured from NHBDs.
authors.affiliation: Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Gu
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
authors.forename: K
authors.initials: K
authors.lastname: Fukunaga
authors.forename: S
authors.initials: S
authors.lastname: Ishiguro
authors.forename: H
authors.initials: H
authors.lastname: Taniguchi
authors.forename: K
authors.initials: K
authors.lastname: Seino
authors.forename: K
authors.initials: K
authors.lastname: Yuzawa
authors.forename: M
authors.initials: M
authors.lastname: Otsuka
authors.forename: T
authors.initials: T
authors.lastname: Todoroki
authors.forename: K
authors.initials: K
authors.lastname: Fukao
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000097:blood; D006085:Graft Survival / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011184:Postoperative Period; D015996:Survival Rate; D013552:Swine; D014019:Tissue Donors; D009927:Tissue and Organ Procurement / Q000379:methods; D014184:Transplantation, Homologous / Q000502:physiology
chemical_list: D010456:Peptides, Cyclic; D010972:Platelet Activating Factor; C088196:TAK 044; D001663:Bilirubin