Endothelin antagonist treatment for successful liver transplantation from non-heart-beating donors

Background. With the shortage of cadaveric donors, non-heart-beating donors (NHBDs) are a potential source of liver allografts, However, warm ischemic injury in NHBDs seriously affects the viability of graft liver. Endothelin (ET)-1 has been reported to be involved in the hepatic microcirculatory di sturbances after ischemia-reperfusion. Methods. In a porcine orthotopic liver transplantation model, changes in th e serum and liver tissue ET-1 concentration were measured and the effects o f an ET receptor antagonist, TAK-044, were evaluated. After cardiac arrest of the donors, liver allografts were subjected to 90 min of warm ischemia, flushed, and preserved for 4 hr at 4 degrees C. The pigs were divided into two groups: a control group (no drug treatment) and a drug-treated group, i n which donors and recipients were treated with TAK-044 (10 mg/kg body, dri p intravenous injection). Both groups had six donor/recipient pairs. Results. The ET-1 concentration in the hepatic venous blood increased after reperfusion of the graft in the control group recipients. ET-1 in the graf t, liver significantly increased during the cold preservation period. TBK-0 44 treatment significantly increased recipient 7-day survival rate. After r eperfusion of the graft, the concentrations of serum liver enzymes and arte rial lactate in the drug-treated group were significantly lower than in the control group. The postoperative increase in portal venous pressure was si gnificantly reduced in the drug-treated group. Measurements of liver enzyme s in the washed-out preservation fluid at the time of graft rinsing indicat ed that TAK-044 treatment of the donors significantly suppressed liver enzy me release during ischemia. Conclusions. These findings indicate TAK-044 treatment has protective effec ts on postoperative function of hepatic allografts procured from NHBDs.