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Hepatic Microcirculatory Dysfunction During Cholestatic Liver Injury in Rats
Author(s) -
ITO YOSHIYA,
BETHEA NANCY W.,
BAKER GREGORY L.,
MCCUSKEY MARGARET K.,
URBASCHEK RENATE,
MCCUSKEY ROBERT S.
Publication year - 2003
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1038/sj.mn.7800208
Subject(s) - cholestasis , microcirculation , intravital microscopy , pathology , medicine , liver injury , sinusoid , hepatic dysfunction , bile duct , in vivo , phagocytosis , ligation , kupffer cell , endocrinology , chemistry , biology , immunology , microbiology and biotechnology
Objective : The present study was conducted to elucidate the sequential alterations in the hepatic microvascular inflammatory response to extrahepatic biliary obstruction. Methods : The hepatic microvasculature in anesthetized Sprague‐Dawley rats was studied by in vivo microscopy 3, 7, and 14 days after bile duct ligation (BDL) or sham operation. Results : The numbers of adhering leukocytes and swollen sinusoidal endothelial cells were significantly increased at 3, 7, and 14 days after BDL when compared with sham‐operated controls. Concomitantly, the numbers of sinusoids containing blood flow were significantly and progressively decreased by up to 30%. The phagocytic activity of hepatic macrophages was significantly elevated during the development of biliary cholestasis. In particular, centrilobular phagocytosis at 14 days after BDL was significantly increased 1.4‐ to 2.0‐fold when compared with that at 3 and 7 days after BDL. Electron microscopy also revealed evidence of activated Kupffer cells reflected by numerous filopodia and ruffles. Conclusions : These results suggest that hepatic microcirculatory dysfunction subsequent to BDL contributes to cholestatic liver injury.