title: An endothelin receptor antagonist ameliorates injuries of sinusoid lining cells in porcine liver transplantation.
abstract: BACKGROUND
  TAK-044 is an endothelin receptor antagonist. Whether the agent has protective effects on liver graft injuries from non-heart-beating donors is unknown.
  
  
  METHODS
  In donor pigs, cardiac arrest was induced by stopping the respirator. Forty-five minutes after cessation of the respirator, the liver was flushed with University of Wisconsin (UW) solution, preserved for 8 hours at 4 degrees C, and transplanted orthotopically. The pigs were divided into two groups: a control group and a drug-treated group in which TAK-044 was given in the UW solutions (10 mg/L) and was administered to recipients (10 mg/kg body weight).
  
  
  RESULTS
  TAK-044 treatment significantly increased recipient survival rate. After reperfusion of the graft, portal venous pressure and 15-minute retention rate of indocyanine green were significantly reduced in the drug-treated group. Electron microscopic findings indicated that TAK-044 attenuated endothelial cell injuries.
  
  
  CONCLUSIONS
  TAK-044 treatment improves the viability of livers harvested from non-heart-beating donors. The main effect of the agent is protection of endothelial cells from ischemia/reperfusion injuries.
authors.affiliation: Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
authors.forename: G
authors.initials: G
authors.lastname: Mei
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: Goto
authors.forename: K
authors.initials: K
authors.lastname: Fukao
mesh_terms: D000818:Animals; D065128:Endothelin Receptor Antagonists; D006085:Graft Survival; D006323:Heart Arrest; D016031:Liver Transplantation / Q000379:methods*; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin / Q000502:physiology; D015427:Reperfusion Injury / Q000517:prevention & control; D013552:Swine; D014019:Tissue Donors
chemical_list: D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C088196:TAK 044