The effect of a prostaglandin I₂analogue (OP-41483) on energy metabolism in liver preservation and its relation to lipid peroxidative reperfusion injury in rats

The effect of the stable prostacyclin (PGI₂) analogue OP-41483 (OP) on liver preservation was investigated in the rat liver transplant model. In a 1-week survival study, 33 orthotopic liver transplants were performed using Wistar rats. In group A, untreated livers were stored with modified UW (mUW) solution at 4°C. In group B, livers from OP-pretreated donors (2 μg/kg, iv) were stored with mUW solution containing OP (1 μg/ml) at 4°C. After 24 h storage, the donor grafts in each group were transplanted to untreated recipients. OP treatment (group B) significantly improved 1-week survival (62.5%, 10/16, P < 0.01 versus group A; 11.8%, 2/17). For the measurement of adenine nucleotides and lipid peroxidation (malondialdehyde, MDA) in liver tissue before preservation, after preservation, and 3 h after transplantation, 20 rat livers in groups A and B were studied. In both groups, the levels of adenosine triphosphate (ATP) declined 6 h after cold preservation, but this degradation of ATP was significantly halted at the level of adenosine monophosphate (AMP) in the OP-treated livers after 24 h of storage. However, OP treatment showed no significant difference in the degree of ATP recovery after transplantation. On the other hand, OP treatment resulted in suppression of the increase in MDA levels and histological amelioration of microcirculatory disturbance 3 h after transplantation. Our data suggested that the combined use of the stable PGI₂analog (OP-41483) and UW solution is beneficial in liver preservation. These mechanisms are discussed in terms of hepatic energy metabolism and lipid peroxidative ischemia/reperfusion injury.