Effect of methylprednisolone on nitrogen dioxide (NO 2)-induced pulmonary edema in guinea pigs

Abstract

The treatment of nitrogen dioxide (NO 2)-induced lung edema is controversial. In addition, mechanisms and patterns of interstitial edema formation in this form of increased permeability edema are unclear. To ascertain if methylprednisolone (MP) is effective in the therapy of NO 2-induced edema, we exposed 108 unaesthetized guinea pigs, in groups of 12, to 277–448 ppm · hr NO 2: in 60, we administered MP just before, and in 48 immediately after exposure. In each group, half the animals were randomly assigned to receive 30 mg/kg MP ip, and the other half saline. Mortality rates and lung water with wet weight/dry weight ( W D ) ratios were calculated. Alveolar edema, periarterial interstitial edema, and NO 2-induced bronchiolitis were graded semiquantitatively by light microscopy from freeze-substituted middle (ML) and lower lobes (LL). We found NO 2 produced an exposure-dependent increase in lung water ( R 0.70, p < 0.01). Treatment with MP preexposure produced a fourfold reduction in mortality, and a significant fall in W D ratios and in alveolar and interstitial edema. No difference in the degree of acute bronchiolitis was found between treated and untreated animals, although ML had significantly more inflammation than LL. Treatment with MP immediately after NO 2 was ineffective since mortality rates, W D ratios, and alveolar and interstitial edema were not lower in the treated animals; there was significantly more interstitial edema in the middle lobes of the latter. Both LL and ML had equally abundant alveolar edema, but LL had significantly more interstitial edema, supporting our previous findings that in NO 2-induced edema interstitial fluid accumulation follows alveolar flooding, with interlobar discrepancies probably due to differences in lung volume or in ventilation.