The protective effect of thromboxane A2 synthetase inhibitor against ischemic liver injury.

To evaluate the role of thromboxane A2 (TXA2) in ischemic liver injury, the serum changes in thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-K-PGF1 alpha) following warm ischemia of the total canine liver were examined, and the protective effect of a TXA2 synthetase inhibitor was assessed. Total liver ischemia was performed for 60 min on two groups of dogs: a control group, in which ischemia alone was performed, and an OKY-046 group, which received a TXA2 synthetase inhibitor. A temporary active portacaval shunt was used to eliminate the effects of splanchnic venous stasis during clamping of the hepatic pedicle. Postoperative changes in liver function, assessed by the transaminase enzyme levels, and in prostaglandins were recorded and the histologic liver findings of both groups 1 week after ischemia were compared. The levels of 6-K-PGF1 alpha increased after reperfusion in both groups, while those of TXB2 increased in the control group but maintained low levels in the OKY-046 group. Liver function was better and histologic changes less marked in the OKY-046 group than in the control group, suggesting the important role of TXA2 in ischemic liver injury and the usefulness of a TXA2 synthetase inhibitor for protecting the liver against ischemic injury.