An endothelin receptor antagonist ameliorates injuries of sinusoid lining cells in porcine liver transplantation.
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.
Fukunaga
K
K
Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
Takada
Y
Y
Mei
G
G
Taniguchi
H
H
Seino
K
K
Yuzawa
K
K
Otsuka
M
M
Todoroki
T
T
Goto
K
K
Fukao
K
K
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
D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C088196:TAK 044