Figure 1.

Countercurrent blood flow and physiological hypoxia in the healthy intestinal mucosa. (a) A model of blood flow dynamics in the healthy intestinal mucosa. Countercurrent blood flow reduces local pO₂ along the crypt-villus axis and results in low pO₂ at the villus tip. (b) The mechanism of nitroimidazole dye retention in hypoxic regions. These imidazole derivatives (R-NO₂) are taken into cells passively and reduced to highly reactive nitrogen intermediates ( $\text{R-}{\text{NO}}_2^{-·}$) within the cytoplasm. In the absence of adequate O₂ to regenerate the native compound, these intermediates react with thiol groups in proteins, peptides, and amino acids to form adducts (R-NH₂) where all atoms of the ring and side chain of the 2-nitroimidazole are retained at pO₂ < 10 mm Hg. The adducts can be visualized through the use of labeled antibodies. (c) Physiological hypoxia. In the colonic mucosa of healthy mice, small amounts of nitroimidazole adduct (red ) are detected along the luminal aspect, suggesting a degree of physiological hypoxia in the normal colon. Abbreviation: pO₂, partial oxygen pressure.