Hepatic microvascular dysfunction endotoxemic rats after acute ethanol administration

Yoshinori Horie, Shinzo Kato, Eiji Ohki, Hironao Tamai, Yoshiyuki Yamagishi, Hiromasa Ishii

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: A high concentration of ethanol is reported to cause hepatic microvascular dysfunction. However, little is known about the effect of ethanol on hepatic microcirculation in endotoxemic animals. The objective of this study was to determine whether endotoxemia enhances the hepatic microvascular dysfunction induced by acute ethanol administration. Methods: Intravital videomicroscopy was used to monitor leukocyte recruitment, number of nonperfused sinusoids, and flow velocity of erythrocytes (RBC) labeled with fluorescein isothiocyanate (FITC) in the livers of male Wistar rats that were administered ethanol (20%, 3 g/kg; or 40%, 6 g/kg) from a gastric tube. Flow velocity of RBC in sinusoids was measured with an off-line velocimeter. Plasma tumor necrosis factor (TNF)-α levels were also measured. In some experiments, rats were injected with 2 mg/kg of lipopolysaccharides (LPS) intraperitoneally at 16 hr before the experiments, and the same protocol was performed. Results: Although FITC-RBC velocity was initially increased by both 20% and 40% ethanol in control rats, it was reduced by only 40% ethanol at 60 min. In LPS-treated rats, the FITC-RBC velocity also was increased initially but was reduced at 60 and 30 min by 20% and 40% ethanol, respectively. Only 40% ethanol caused leukostasis in the pericentral region of control rats. In LPS-treated rats, however, leukostasis was noted in the midzonal and pericentral regions of liver after both 20% and 40% ethanol administration. Ethanol increased plasma TNF-α levels only in LPS-treated rats. Conclusions: These results suggest that LPS synergistically enhances ethanol-induced hepatic microvascular dysfunction and liver injury, especially in the midzonal region via coagulation, which may be mediated by TNF-α.

Original languageEnglish
Pages (from-to)691-698
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume24
Issue number5
DOIs
Publication statusPublished - 2000 May

Keywords

  • Endotoxin
  • Erythrocyte Velocity
  • Hepatocellular Injury
  • Intravital Microscope
  • Tumor Necrosis Factor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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