ALCOHOL-OXYGEN TENSION INTERACTIONS IN LIVER

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A major question in the area of ethanol-induced liver damage relates to the role of oxygen deprivation in compromising the viability of the tissue. Previous studies from our laboratory suggest that hepatocytes from ethanol-fed animals cannot maintain an adequate energy state when oxygen deficient. In the present study we will determine whether chronic ethanol consumption makes the intact liver more susceptible to hypoxic damage. A powerful approach to this problem is to monitor the levels of hepatic energy metabolites using 31P-NMR spectroscopy while varying the oxygen tension of the perfusate entering an isolated liver. Experiments are proposed to systematically investigate the effects of hypoxia, acute doses of ethanol, and combinations of the two, on the energy state of perfused livers from both ethanol-fed and control animals. The utilization of oxygen by the liver under all the conditions imposed will be determined by continuous measurements of influent and effluent oxygen tension using micro oxygen electrodes. The study proposed is unique in that it will allow continuous monitoring of high energy phosphorus metabolites and oxygen utilization in the liver under conditions ere nutrient availability and oxygen tension are stringently controlled. This will allow us to establish the relationships between oxygen tension, ethanol metabolism, oxygen utilization and energy state in livers of animals that are chronic ethanol consumers. This study is relevant to the human condition where it has been demonstrated in alcoholics with hepatic necrosis that there can be reductions in hepatic venous oxygen tension.