We conclude that PGE1 protects the liver against ischemia-reperfusion injury by reducing leukocyte-endothelial cell adhesion via down-modulation of ICAM-1 expression on the endothelium.

Sinusoidal endothelial cell injury plays a pivotal role in anoxidreoxygenation liver damage. However, the mechanisms culminating in anoxidreoxygenation endothelial cell injury remain unclear. Our aims were to determine whether anoxidreoxygenation injury of sinusoidal endothelial cells causes mitochondrial dysfunction. In cultured rat liver sinusoidal endothelial cells, the mitochondrial membrane potential, cytosolic free calcium and cytosolic pH were quantitated by means of fluorescent probes and multiparameter digitized video microscopy. Cell viability was measured on the basis of lactate dehydrogenase release, and ATP was quantitated with a luciferin/luciferase assay. Mitochondrial membrane potential was stable during 90 min of aerobic perfusion. After 60 and 90 min of anoxia, mitochondrial membrane potential decreased gradually to 97% f 6% and 79% f 7% of the basal value, respectively. However, mitochondrial membrane potential decreased abruptly with reoxygenation after 60 min of anoxia to 45% f 12% of the basal value and did not recover over 30 min of aerobic perifusion. Loss of mitochondrial membrane potential could not be attributed to changes of cytosolic free calcium, cytosolic pH, nitric oxide generation or activity of poly(ADPribose) polymerase. The antioxidants TEMPO (2,2,6,6-tetramethylpiperidine-N-owl) and Trolox (6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid) protected against both loss of mitochondrial membrane potential and cell viability. In contrast, reduced glutathione depletion by diethyl maleate or phorone potentiated mitochondrial depolarization and cell killing. Cyclosporine plus trifluoperazine also protected against loss of mitochondrial membrane potential and cell killing, suggesting that the mitochondrial membrane permeability transition was respon-

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