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.

Abstract

Pyridine nucleotide fluorescence made from the surface of the Hb-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 O2 tension at which pyridine nucleotide reduction first occurred in pericentral regions, the O2 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 O2 gradient from 275 to 400 torr (1 torr = 133 Pa [pascal]), primarily due to the increase in the O2 gradient in pericentral regions. Ethanol treatment also increased hepatic O2 uptake significantly, from 110 to 144 (.mu.mol/g per h). Treatment with the antithyroid drug 6-propyl-2-thiouracil reversed the effect of ethanol on O2 uptake and on the lobular O2 gradient. The O2 gradients measured with the micro-light guide were confirmed by direct measurement of tissue O2 tensions in periportal and pericentral areas by using an O2 electrode. These data were consistent with the hypothesis that chronic treatment with ethanol caused the pericental region of the liver lobule to become susceptible to hypoxic cellular injury. This may have been responsible for the localized hepatotoxic effects of ethanol.