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- W2410004675 abstract "Accumulation and adherence of leukocytes within the hepatic microvasculature have been emphasized to play a major role in the pathogenesis of endotoxin/lipopolysaccharide (LPS)-induced liver injury. However, there is no information on their interrelation with hepatic microvascular perfusion failure, hepatocellular damage and liver dysfunction following LPS exposure.Therefore, we quantitatively assessed the initial LPS-induced hepatic microvascular response, including leukocyte-endothelium interaction and their interrelation with sinusoidal perfusion, hepatocellular integrity (serum AST/ALT activity) and excretory function (bile flow). After infusion of LPS (E. coli 0128:B12; 10 mg.kg-1 i.v.) intravital fluorescence microscopy was applied to livers of Sprague-Dawley rats.1 h after LPS exposure deterioration of hepatic microcirculation was hallmarked by significant accumulation of leukocytes, stagnant within sinusoids and adherent to the endothelial lining of postsinusoidal venules. This was accompanied by a progressive increase of the number of non-perfused sinusoids (20 +/- 4%). During the 1 h period after LPS exposure, bile flow was found significantly (p < 0.05) reduced, while serum AST/ALT activities remained unchanged. Leukocytes appear to contribute to sinusoidal perfusion failure, since the number of non-perfused sinusoids significantly (p < 0.01) correlated with the number of leukocytes stagnant within the sinusoids. In addition, the inverse correlation (p < 0.01) of bile flow with the number of both, leukocytes stagnant within the sinusoids and non-perfused sinusoids indicates that microvascular injury initiates hepatic dysfunction.Inasmuch as LPS exposure initially induces only microcirculatory disturbances without substantial loss of hepatocellular integrity, we propose that therapeutic strategies during early endotoxemia should focus on attenuation of microvascular injury to prevent manifestation of hepatocellular damage." @default.
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- W2410004675 date "1993-01-01" @default.
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- W2410004675 title "Role of leukocytes in the initial hepatic microvascular response to endotoxemia." @default.
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