Periportal and Pericentral Pyridine Nucleotide Fluorescence from the Surface of the Perfused Liver: Evaluation of the Hypothesis That Chronic Treatment with Ethanol Produces Pericentral Hypoxia

Pyridine nucleotide fluorescence made from the surface of the hemoglobin-free perfused rat liver was measured continuously by using a "micro-light guide" placed on selected periportal and pericentral regions of the liver lobule. From the portal oxygen tension at which pyridine nucleotide reduction first occurred in pericentral regions, the oxygen gradient across the liver lobule was estimated in livers from rats treated chronically with ethanol or sucrose. Chronic treatment with ethanol increased the average lobular oxygen gradient from 275 to 400 torr (1 torr = 133 Pa), primarily due to the increase in the oxygen gradient in pericentral regions. Ethanol treatment also increased hepatic oxygen uptake significantly, from 110 to 144 (mumol/g)/hr. Treatment with the antithyroid drug 6-propyl-2-thiouracil reversed the effect of ethanol on O2 uptake and on the lobular oxygen gradient. The oxygen gradients measured with the micro-light guide were confirmed by direct measurement of tissue oxygen tensions in periportal and pericentral areas by using an oxygen electrode. These data are consistent with the hypothesis that chronic treatment with ethanol causes the pericentral region of the liver lobule to become susceptible to hypoxic cellular injury. This may be responsible, at least in part, for the localized hepatotoxic effects of ethanol.