NITROGEN DIOXIDE-INDUCED ACUTE LUNG INJURY IN SHEEP

Lung mechanics; hemodynamics and blood chemistries were assessed in sh eep (Ovis aries) before, and up to 24 h following, a 15-20 min exposur e to either air (control) or approximately 500 ppm nitrogen dioxide (N O2). Histopathologic examinations of lung tissues were performed 24 h after exposure. Nose-only and lung-only routes of exposure were compar ed for effects on NO2 pathogenesis. Bronchoalveolar lavage fluids from air- and NO2-exposed sheep were analyzed for biochemical and cellular signs of NO2 insult. The influence of breathing pattern on NO2 dose w as also assessed. Five hundred ppm NO2 exposure of intubated sheep (lu ng-only exposure) was marked by a statistically significant, albeit sm all, blood methemoglobin increase. The exposure induced an immediate t idal volume decrease, and an increase in both breathing rate and inspi red minute ventilation. Pulmonary function, indexed by lung resistance and dynamic lung compliance, progressively deteriorated after exposur e. Maximal lung resistance and dynamic lung compliance changes occurre d at 24 h post exposure, concomitant with arterial hypoxemia. Bronchoa lveolar lavage fluid epithelial cell number and total protein were sig nificantly increased while macrophage number was significantly decreas ed within the 24 h post-exposure period. Histopathologic examination o f lung tissue 24 h after NO2 revealed patchy edema, mild hemorrhage an d polymorphonuclear and mononuclear leukocyte infiltration. The NO2 to xicologic profile was significantly attenuated when sheep were exposed to the gas through a face mask (nose-only exposure). Respiratory patt ern was not significantly altered, lung mechanics changes were minimal , hypoxemia did not occur, and pathologic evidence of exudation was no t apparent in nose-only, NO2-exposed sheep. The qualitative responses of this large animal species to high-level NO2 supports the concept of size dependent species sensitivity to NO2. In addition, when inspired minute ventilation was used as a dose-determinant, a linear relations hip between NO2 dose and lung resistance was found. The importance of these findings, NO2 dose-determinants, and the utility of sheep as a l arge animal inhalation model are discussed.