Ethanol-induced changes in the intralobular oxygen gradient of perfused rat liver

A new tissue fluorometric method was developed to estimate the intralobular oxygen gradient in hemoglobin-free perfused rat liver. The method employs a two-branch micro-light guide with a tip diameter of 170 mu. With this light guide, it was possible to measure pyridine nucleotide fluorescence (366 nm leads to 450 nm) from periportal and pericentral regions of the liver lobule. By measuring inflow PO2 values at which pyridine nucleotide fluorescence increased in the pericentral regions of the liver lobule, the mean intralobular oxygen gradient was estimated. The measured gradient was approximately 180 torr in livers from sucrose-treated control rats. Chronic treatment with ethanol increased both the mean intralobular oxygen gradient and the rate of hepatic oxygen uptake by 30%. The antithyroid drug, 6-propyl-2-thiouracil, completely reversed the effects of ethanol on both the intralobular oxygen gradient and the rate of oxygen uptake. These data present direct physical evidence that the increased tissue respiration induced by chronic ethanol treatment indeed accentuates the intralobular oxygen gradient and thus support the hypothesis that selective depletion of oxygen in the pericentral region of the liver lobule may underlie ethanol-induced cellular injury confined to this site.