POTENTIATION OF BLEOMYCIN-INDUCED LUNG INJURY BY EXPOSURE TO 70-PERCENT OXYGEN - MORPHOLOGIC ASSESSMENT

Abstract

The effects of a single intratracheal instillation of [the antineoplastic drug] bleomycin followed by exposure to 70% O2 for 72 h were studied in hamsters. Mortality increased markedly among hamsters exposed to 70% O2 for 72 h after bleomycin instillation, compared with animals receiving bleomycin and breathing room air. The lethal dose required to kill 50% of the hamsters at 30 days (LD50, 30 day) for bleomycin alone was 0.73 U/100 g body wt; the LD50, 30 day for bleomycin followed by 70% O2 fell to 0.23 U/100 g body wt. Using morphometry and light microscopy, the amount of diseased lung increased in hamsters given bleomycin with hyperoxia compared with that in those treated with bleomycin alone. After 0.20 U bleomycin and air, 2.8 .+-. 1.6% of the lung was abnormal; with 0.20 U bleomycin followed by 70% O2, 42.7 .+-. 17.9% of the lung was abnormal. At bleomycin doses that produced no apparent lesions, the addition of 70% oxygen for 72 h produced focal interstitial fibrosis at 30 days. Neither mortality nor significant histologic changes were seen in hamsters treated with saline followed by exposure to 70% O2 for 72 h. Hyperoxia apparently potentiates bleomycin damage; the use of elevated O2 concentrations in patients being treated with bleomycin probably should be minimized.