Hepatic microcirculatory dysfunction during cholestatic liver injury in rats.
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. Microcirculation (2003) 10, 421-432. doi:10.1038/sj.mn.7800208
Ito
Yoshiya
Y
Department of Cell Biology Anatomy, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Bethea
Nancy W
NW
Baker
Gregory L
GL
McCuskey
Margaret K
MK
Urbaschek
Renate
R
McCuskey
Robert S
RS
D000818:Animals; D002448:Cell Adhesion; D001651:Cholestasis, Extrahepatic / Q000473:pathology / Q000503:physiopathology*; D004731:Endotoxins / Q000097:blood; D007962:Leukocytes / Q000473:pathology; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008102:Liver Circulation / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000473:pathology / Q000503:physiopathology; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins