Ethanol-induced disturbance of hepatic microcirculation and hepatic hypoxia.
The hypothesis was tested whether ingestion of ethanol might disturb the hepatic microcirculation with resulting hepatic hypoxia. Infusion of ethanol increased the portal pressure concentration-dependently in rat livers perfused with Krebs-Henseleit buffer at a constant flow rate (Emax = 11.5 cm H2O, EC50 = 90 mM). This increase in portal pressure was due to hepatic vasoconstriction, since it diminished in the presence of sodium nitroprusside, a direct acting vasodilator. The regional hepatic tissue hemoglobin concentration after perfusion with added erythrocyte suspension (hematocrit 1%), measured by tissue-reflectance spectrophotometry, was significantly diminished by the infusion of ethanol, indicating the impairment of the microcirculation of the superficial layer of the liver. When the absorption spectrum of the liver was examined by reflectance spectrophotometry, infusion of ethanol caused a parallel reduction of all the mitochondrial respiratory cytochromes in a concentration-dependent fashion, concomitant with the increase of portal pressure, indicating a marked reduction of oxygen concentration in superficial liver tissue. The reduction of the respiratory cytochromes was also associated with the decrease in oxygen consumption of the liver, indicating that the hepatic hypoxia was due to the reduction of oxygen delivery to hepatocytes rather than the increased oxygen consumption of the liver. The reduction of the respiratory cytochromes was correlated with the increase in portal pressure and was inhibited by sodium nitroprusside. These data indicate that the ethanol-induced hepatic vasoconstriction disturbs hepatic microcirculation, resulting in hepatic hypoxia and reduction of mitochondrial respiratory cytochromes.
Hijioka
T
T
First Department of Medicine, Osaka University Medical School, Japan.
Sato
N
N
Matsumura
T
T
Yoshihara
H
H
Takei
Y
Y
Fukui
H
H
Oshita
M
M
Kawano
S
S
Kamada
T
T
D000818:Animals; D001794:Blood Pressure; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D000860:Hypoxia / Q000139:chemically induced*; D008099:Liver / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D010101:Oxygen Consumption; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction
D000431:Ethanol