Biliary obstruction exacerbates the hepatic microvascular inflammatory response to endotoxin.
Gram-negative sepsis is a serious complication for patients with obstructive jaundice. The present study was conducted to elucidate the response of hepatic microcirculation to endotoxin 2 weeks after bile duct ligation (BDL) or sham-operation in rats. Two hours after lipopolysaccharide (LPS) injection (1, 10, or 100 microg/kg, iv.), the hepatic microvasculature was examined using in vivo microscopy. BDL elicited increases in leukocytes adhering to the sinusoidal wall, swelling of sinusoidal endothelial cells as well as phagocytic activity of hepatic macrophages and a decrease in the numbers of perfused sinusoids. LPS (1, 10, 100 microg/kg) further increased leukocyte adhesion and reduced the numbers of perfused sinusoids in a dose-dependent manner. Leukocyte adhesion in response to LPS (1, 10, 100 microg/kg) in BDL rats was increased 6.1-fold, 5.9-fold, and 3.3-fold, respectively when compared with sham-operated rats. The numbers of perfused sinusoids in response to LPS (1, 10, 100 microg/kg) in BDL rats were decreased by 42%, 36%, and 45%. While 1 and 10 microg/kg LPS also elicited an increase in phagocytic activity in BDL rats when compared with sham-operated rats, the response to 100 microg/kg LPS was suppressed. LPS did not affect the numbers of swollen endothelial cell in BDL rats. The present study demonstrated that chronic biliary obstruction enhanced the hepatic microvascular response to low doses of endotoxin. This observation suggests that exaggerated hepatic microcirculatory dysfunction during sepsis contributes to the development of liver injury and a high incidence of morbidity and mortality in biliary obstruction.
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Department of Cell Biology and Anatomy, College of Medicin, University of Arizona, Tucson 85724, USA.
Machen
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Urbaschek
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McCuskey
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D000818:Animals; D002779:Cholestasis / Q000150:complications*; D004727:Endothelium / Q000187:drug effects / Q000473:pathology; D004731:Endotoxins / Q000633:toxicity*; D006505:Hepatitis / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000209:etiology
D004731:Endotoxins; D008070:Lipopolysaccharides