EFFECTS OF 0.25 PPM NITROGEN-DIOXIDE ON THE DEVELOPING MOUSE LUNG .2.QUANTITATION OF ELASTIC TISSUE AND ALVEOLAR WALLS

A colony of 3-wk-old mice (Swiss-Webster) was divided into young adult mice exposed to intermittent 0.25 ppm NO2 for 6 wk and a control grou p. The left lungs of 186 control and 186 exposed animals were perfused -inflated with glutaraldehyde at 6, 10, and 32 wk postexposure, and el astic fibers in paraffin sections were stained with aldehyde fuchsin. Image analysis quantitation of elastin content at the first test perio d showed significant increases in lung elastin for the NO2-exposed ani mals, that is, fiber number (p =.001), elastin area (p = .007), and el astin alveolar perimeters (p <.008). Internal surface area (alveolar w all perimeters) decreased (p =.05) and lung volume increased slightly but not significantly. There were also nonsignificant trends toward a larger fiber size, and higher elastic fiber/wall area ratios. A revers al occurred at the 10-wk postexposure test. All elastic fiber measurem ents for the exposed animals were significantly less than those for th e control group, namely, elastic fiber numbers (p <.02), area per fiel d (p <.005), intercepts (p =.006), perimeters (p <.02), and mean size (p <.04). There was also a decrease in nonelastin and total alveolar w all area, but at borderline levels of significance (p =.1, p <.07, res pectively). At the 32-wk postexposure test, the findings reversed in p art, with the exposed animals showing a trend toward an increase in el astin fiber number (p =.09) and elastin area (p = .1) bur with nonelas tin alveolar wall area still less than control values (p <.06). A high ly significant finding was an interaction between the increase in elas tin and the fall in nonelastin alveolar wall area, namely, increases f or the exposed animals in ratios of elastic fiber number to alveolar w all area and alveolar fiber area to alveolar wall area, p <.003 and p <.02, respectively. The altered relationship of alveolar wall componen ts may in part account for the Type 2 cell hyperplasia noted in Part 1 of the study, that is, an intact lung scaffolding is essential for co mplete restoration of an injured epithelial lining. The sequence of ev ents over the three test periods suggest that an ambient level of NO2 exposure has injured both elastin and nonelastin components of the alv eolar wall. The presence of alterations at 32 wk postexposure, includi ng data from Part 1 of the study, further suggests that both the epith elium and connective tissue have sustained some irreversible damage.