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°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. Conclusion: 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.