BENEFICIAL EFFECT OF THROMBOXANE A2 SYNTHETASE INHIBITOR ON COLD-STORED RAT-LIVER

Prostanoids such as prostacyclin and thromboxane A(2) have recently be en suggested to play important roles in cold ischemia/reperfusion inju ry. The purpose of this study was to investigate the effect of thrombo xane A(2) synthetase inhibitor (OKY-046) on cold-stored livers of the rat using an ex vivo perfusion system. Addition of OKY-046 to preserva tion solution and the perfusate of livers stored cold (4 degrees C) in lactated Ringer's solution resulted in significantly lower glutamic p yruvic transaminase release (3.01+/-0.86 IU/g liver vs. 1.79+/-1.08 IU /g liver at 120 min after perfusion; P<0.05), reduced perfusate ammoni a levels (8.51+/-2.51 mu g/dl/g liver vs. 3.62+/-1.71 mu g/dl/g liver at 60 min; P<0.05 and thereafter), lower perfusate taurocholate levels (0.63+/-0.10 vs. 0.18+/-0.05 at 15 min; P<0.01 and thereafter), perfu sate hyaluronic acid clearance (0.934+/-0.132 vs. 0.76+/-0.127 at 30 m in; P<0.05 and thereafter), and a reduced number of trypan blue-positi ve sinusoidal lining cells (50.1+/-9.9%; vs. 17.4+/-7.0%; P<0.01). His tologically, the liver preserved for 6 hr in simple cold lactated Ring er's solution exhibited interstitial edema, various degrees of hepatoc yte swelling, and sinusoidal stenosis, as well as dilatation, while th e livers treated with OKY-046 demonstrated much less hepatocyte swelli ng, and change in sinusoidal width was nearly absent. We conclude that OKY-046 reduces post-preservation reoxygenation injury by protecting sinusoidal endothelial cells and hepatocytes.