Effect of size on portal circulation of hepatic nodules from carcinogen-treated rats.

The portal circulation of diethylnitrosamine-initiated nodules (0.5 to 7 mm in diameter) was studied in rat livers perfused exclusively via the portal vein. Microlight guides were placed on normal and nodular tissue on the capsular surface of the liver to measure pyridine nucleotide fluorescence (366 leads to 450 nm). When oxygen tension of the inflow perfusate was lowered, fluorescence in both normal tissue and small nodules (less than 2 mm in diameter) increased sharply due to the reduction of pyridine nucleotides, indicating previous normoxia. In contrast, similar manipulations did not increase fluorescence in nodules greater than 2 mm in diameter, demonstrating that nicotinamide adenine dinucleotide was reduced maximally previously; i.e., the nodules were anoxic. Direct measurements of nodule oxygen concentrations with a miniature oxygen electrode confirmed these results. 7-Hydroxycoumarin or fluorescein could be detected with micro-light guides in normal tissue and nodules less than 2 mm in diameter but not in nodules greater than 2 mm in diameter. Furthermore, fluorescent microscopy indicated an absence of fluorescein in nodules greater than 2 mm in diameter. Therefore, with four independent optical and polarographic techniques, we have demonstrated reduced portal circulation in nodules greater than 2 mm in diameter; however, smaller nodules could not be differentiated from normal tissue.