Modification of oxygen toxicity after lung injury by bleomycin in hamsters

In order to explore the interactions between oxygen toxicity and a model of interstitial pulmonary fibrosis, we studied the effects of exposure to 100% O2 at 1 atmosphere and exposure to 60% O2 for 21 days on survival, lung statics, and lung weight in hamsters previously treated intratracheally with bleomycin sulfate for 8 days (BLEO-8) and for 21 days (BLEO-21). All 10 saline-treated control animals died between 5 and 7.5 days in 100% O2; 7 of 15 BLEO-8 hamsters died before Day 5 (Fisher's exact test, p = 0.01) and 7 BLEO-21 hamsters died after Day 7.5 (Fisher's exact test, p = 0.03). Five of 11 BLEO-8 hamsters died in 60% O2, but there were no deaths among 8 BLEO-21 hamsters so exposed (Fisher's exact test, p = 0.04). There were slight decreases in the volume of air in the lungs at 25 cm H2O transpulmonary pressure (TLC25), vital capacity (VC), and quasi-static lung compliance (Cst(L)) in the saline-treated hamsters breathing 60% O2, compared with air-breathing control animals. The BLEO-8 animals exposed to 60% O2 showed greater decreases in TLC25, VC, and Cst(L) than the air-breathing control animals, and the mean dry lung weight of the O2-breathing group was significantly greater than that of the control animals. The BLEO-21 hamsters exposed to 60% O2 showed only a 15 to 18% greater decrease in TLC25, VC, and Cst(L) than the air-breathing control animals; the mean dry lung weight of the O2-breathing group was similar to the air-breathing control group. We concluded that the breathing of either 100 or 60% O2 adds to the severity of the lung injury previously induced by bleomycin; the degree of worsening is greater at 8 days than at 21 days after bleomycin treatment. These findings suggest that concentrations of inhaled oxygen used in treating human interstitial lung diseases should be kept at the lowest levels compatible with adequate tissue oxygenation.