Progressive pulmonary fibrosis in hamsters.

The concomitant treatment of hamsters with bleomycin and hyperoxia results in a synergistic development of pulmonary injury. We exposed hamsters for 72 hr to 70% oxygen following a single intratracheal instillation of bleomycin (0.16 U/100 g body weight). Groups of 10 animals were killed at 3, 6, 10, 30, 60, 90, and 120 days after instillation for histopathologic and morphometric assessment. Diffuse alveolar damage developed acutely. At 30 days, the intense acute cellular infiltrate had subsided, leaving a focal interstitial pneumonitis. Morphometric quantitation at 10 days revealed that 33.5 +/- 5.3% (x +/- SE) of the lung was diseased; there was apparent healing by 30 days, when 10.5 +/- 2.0% of the lung was diseased. However, progression to diffuse pneumonitis with fibrosis was seen at 60, 90, and 120 days, when 30.2 +/- 4.9%, 38.5 +/- 5.8%, and 38.8 +/- 4.5% of the lung was diseased, respectively. In vivo pulmonary function studies on treated animals at 25 and 55 days showed decreasing dynamic compliance and increased minute ventilation, which corroborates the presence of interstitial fibrosis. We conclude that simultaneous treatment of hamsters with bleomycin and hyperoxia results in interstitial fibrosis with a distribution and progression that mimics human pulmonary fibrosis. This model appears ideally suited for the study of progressive fibrosis and will be useful when development of a widely distributed lesion is crucial.