Nitrogen dioxide-induced acute lung injury in sheep

Abstract

Lung mechanics, hemodynamics and blood chemistries were assessed in sheep ( Ovis aries) before, and up to 24 h following, a 15–20 min exposure to either air (control) or approximately 500 ppm nitrogen dioxide (NO 2). Histopathologic examinations of lung tissues were performed 24 h after exposure. Nose-only and lung-only routes of exposure were compared for effects on NO 2 pathogenesis. Bronchoalveolar lavage fluids from air-and NO 2-exposed sheep were analyzed for biochemical and cellular signs of NO 2 insult. The influence of breathing pattern on NO 2 dose was also assessed. Five hundred ppm NO 2 exposure of intubated sheep (lung-only exposure) was marked by a statistically significant, albeit small, blood methemoglobin increase. The exposure induced an immediate tidal volume decrease, and an increase in both breathing rate and inspired minute ventilation. Pulmonary function, indexed by lung resistance and dynamic lung compliance, progressively deteriorated after exposure. Maximal lung resistance and dynamic lung compliance changes occurred at 24 h post exposure, concomitant with arterial hypoxemia. Bronchoalveolar lavage fluid epithelial cell number and total protein were significantly increased while macrophage number was significantly decreased within the 24 h post-exposure period. Histopathologic examination of lung tissue 24 h after NO 2 revealed patchy edema, mild hemorrhage and polymorphonuclear and mononuclear leukocyte infiltration. The NO 2 toxicologic profile was significantly attenuated when sheep were exposed to the gas through a face mask (nose-only exposure). Respiratory pattern was not significantly altered, lung mechanics changes were minimal, hypoxemia did not occur, and pathologic evidence of exudation was not apparent in nose-only, NO 2-exposed sheep. The qualitative responses of this large animal species to high-level NO 2 supports the concept of size dependent species sensitivity to NO 2. In addition, when inspired minute ventilation was used as a dose-determinant, a linear relationship between NO 2 dose and lung resistance was found. The importance of these findings, NO 2 dose-determinants, and the utility of sheep as a large animal inhalation model are discussed.