title: Ethanol exacerbates hepatic microvascular dysfunction, endotoxemia, and lethality in septic mice.
abstract: The effect of acute ethanol administration on the hepatic microvascular responses to sepsis was studied. Polymicrobial sepsis was induced 30 min after mice had received ethanol (1 g/kg b.w.) or isocaloric maltose-dextrin by gastric gavage. Lethality within 24 h was 91.7% in the ethanol-treated animals and 40.0% in septic controls. Endotoxin levels in ethanol treated animals were 107 pg/ml at 6 hr and 1205 pg/ml at 12 h, compared with 32 pg/ml and 104 pg/ml, respectively in the controls. In vivo microscopy revealed that at 3 h in the ethanol treated septic animals, Kupffer cell phagocytic activity was increased by 41%, whereas the number of sinusoids containing blood flow were reduced by 34% concomitant with a 144% increase in the adherence of leukocytes to the sinusoidal walls when compared with the septic controls. By 6 h, however, Kupffer cell phagocytic activity was reduced by 48% in the ethanol treated animals; this was accompanied by a further deterioration in sinusoidal blood flow. Thus, a small, acute dose of ethanol causes significant impairment of the hepatic microcirculation followed by suppression of Kupffer cell activity. This results in exacerbation of endotoxemia and lethality during polymicrobial sepsis.
authors.affiliation: Department of Anatomy, College of Medicine, University of Arizona, Tucson 85724, USA.
authors.forename: J
authors.initials: J
authors.lastname: Nishida
authors.forename: W
authors.initials: W
authors.lastname: Ekataksin
authors.forename: D
authors.initials: D
authors.lastname: McDonnell
authors.forename: R
authors.initials: R
authors.lastname: Urbaschek
authors.forename: B
authors.initials: B
authors.lastname: Urbaschek
authors.forename: R S
authors.initials: RS
authors.lastname: McCuskey
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000097:blood; D000431:Ethanol / Q000633:toxicity*; D007728:Kupffer Cells / Q000473:pathology; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects*; D010587:Phagocytosis; D018805:Sepsis / Q000401:mortality / Q000503:physiopathology*
chemical_list: D004731:Endotoxins; D000431:Ethanol