The effect of bleomycin and oxygen on rat lung.

The interaction of bleomycin and oxygen on rat lung was studied by giving endotracheal injections of bleomycin or saline to rats which subsequently breathed air or oxygen for 24 or 48 h. In the first protocol bleomycin or saline treated rats were exposed to 24 h of air or 100% oxygen and then breathed air for a further 6 d after which they were killed. In the second protocol bleomycin or saline treated rats were exposed to 48 h of air or up to 48 h of 100% oxygen. All animals in this protocol either died or were killed at the 48 h time point. The lungs were fixed in full inflation and 6 histological sections prepared from each. The volume densities of alveolar air, duct air, alveolar walls, intra-alveolar cells and non-parenchyma were quantitated using standard point counting techniques. In addition, the percent of alveoli containing fibrin was determined. The results demonstrated a synergistic effect of oxygen and bleomycin toxicity after both 24 and 48 h oxygen exposure. This was most marked for alveolar fibrin deposition which was significantly greater (p less than 0.001) in the bleomycin and oxygen groups than the saline/air, saline/oxygen or bleomycin/air groups. In the 48 h study the volume density of intra-alveolar cells was also significantly greater in the bleomycin/oxygen group than all other groups (p less than 0.05). It is concluded that bleomycin and oxygen exhibit synergistic toxic effects and that their concurrent administration should be avoided.