Hepatic microvascular dysfunction in endotoxemic rats after acute ethanol administration.
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)-alpha 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-alpha 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-alpha.
Horie
Y
Y
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Kato
S
S
Ohki
E
E
Tamai
H
H
Yamagishi
Y
Y
Ishii
H
H
D000818:Animals; D001783:Blood Flow Velocity; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects*; D000431:Ethanol / Q000009:adverse effects*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000098:blood supply / Q000187:drug effects*; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism; D017082:Portal Pressure / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D002492:Central Nervous System Depressants; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol