Effects of thromboxane A(2) synthesis inhibitor (OKY-046) on total liver ischemia in rats

Background. The purpose of this study was to determine the effects of OKY-046, a thromboxane A(2) (TxA(2)) synthesis inhibitor, on the hepatic dysfunction produced in rats by liver cell ischemia and reperfusion injury. Methods. Total warm ischemia of the liver was induced by the Pringle maneuver for a period of 45 minutes. The animals were divided into two groups; the OKY-046 group, and the control group. These were further divided into three subgroups according to the reperfusion time (5, 30, and 60 minutes). OKY-046 was administered via the femoral vein at a rate of 100 mu g/kg/min, beginning 20 minutes prior to portal and hepatic arterial cross-clamping, continuing to the termination of the experiment. Results. The ratio of thromboxane B-2 (TxB(2)) to 6-keto-prostaglandin F-1 alpha (6 keto PGF(1 alpha)) ratio in the liver tissue was lower in the OKY-046 group compared to the control group. Significant differences in the hydrous volume of the liver and in the mitochondrial score were noted between the OKY-046 and control groups, indicating liver preservation by OKY-046. Conclusions. The mechanism of this effect is postulated to be inhibition of the synthesis of TxA(2) and enhancement of the levels of endogenous prostacyclin (PGI(2)). The resulting improvement in the TxA(2) to PGI(2) balance associated with OKY-046 administration may prevent liver damage in this model.