Abstract
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 vivomicroscopy 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. Microcirculation(2003) 10,421–432. doi:10.1038/sj.mn.7800208