Incomplete compensation of enhanced hepatic oxygen consumption in rats with alcoholic centrilobular liver necrosis.
Centrilobular hypoxia mediated by enhanced hepatic consumption of oxygen has been hypothesized to be a factor of pathogenetic importance in ethanol-induced liver injury. In the present study, this hypothesis was tested in a rat model which developed alcoholic centrilobular liver necrosis. Male Wistar rats were infused with high fat diet plus ethanol or isocaloric glucose for 7 weeks, a duration which resulted in induction of balloon cell degeneration, focal necrosis, and inflammation in the centrilobular region of the liver of the ethanol-fed animals. Hepatic blood flow, oxygen consumption and oxygen delivery were determined by the radiolabeled microsphere method and measurement of oxygen content in arterial, portal venous, and hepatic venous blood. Hepatic oxygen consumption was markedly increased by 159% in the ethanol-fed animals compared to that in the controls when results were expressed as relative to body weight. Even after these results were standardized per gram of liver weight, hepatic oxygen consumption was still significantly elevated in the ethanol-fed group, but the magnitude of the elevation was reduced to 70%, due to marked hepatomegaly observed in these animals. There was a concomitant 59% increase in hepatic oxygen delivery in the ethanol-fed rats when expressed per kilogram of body weight, and this effect was attributable entirely to increased portal blood flow. However, the increment of this increase in oxygen delivery was much too small to compensate for the 159% increase in oxygen consumption. In addition, this increase in hepatic oxygen delivery was no longer observable when the results were reexpressed based on the liver weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Tsukamoto
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Hepatopancreatic Research Laboratory, Veterans Administration Medical Center, Martinez, California 94553.
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D000818:Animals; D001835:Body Weight; D006503:Hepatic Veins; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008102:Liver Circulation; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009336:Necrosis; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains
D010100:Oxygen