PROTECTIVE EFFECTS OF ANTITHROMBIN-III SUPPLEMENTATION ON WARM ISCHEMIA AND REPERFUSION INJURY IN RAT-LIVER

The effect of antithrombin III (AT III) supplementation on energy stat us, microcirculation, cytoprotection, and prostacyclin (PGI2) producti on during and after a period of warm ischemia of the rat liver was inv estigated. AT III supplementation (250 units/kg) stimulate prostagland in I-2 (PGI(2)) production from 1 hour after administration, with maxi mal production observed at 3 hours. Ischemia was induced by occluding the hepatoduodenal ligament for 30 minutes, and experiments were conti nued for 60 minutes after reperfusion. The rats received AT III (250 u nits/kg IC) 30 minutes before induction of liver ischemia (AT III grou p). In the AT III group, recovery of the beta-ATP/inorganic phosphate ratio measured by P-31 nuclear magnetic resonance showed significant i mprovement (p < 0.01), and the recovery of tissue blood flow markedly improved (p < 0.01) compared to the saline-treated group (control grou p). Leakages of aspartame aminotransferase, alanine aminotransferase, and lactate dehydrogenase were mitigated in the AT III group (p < 0.05 ). Ultrastructural alterations of sinusoidal endothelial cells were ma rkedly reduced in the AT III group. The PGI(2) level at the end of rep erfusion was significantly elevated (p < 0.01) in the AT III group com pared to the control group. The results of this study indicated that p retreatment with AT III significantly improved the energy status and m icrocirculation, as well as histologic damage, after liver ischemia an d reperfusion. One of the fundamental effects of AT III might be media ted through the production of prostacyclin.