Intravenous bleomycin does not alter the toxic effects of hyperoxia in rabbits.

The purpose of this study was to test the hypothesis that bleomycin administration enhances the toxic effects of oxygen on the respiratory system. Twenty-one rabbits, with no evidence of respiratory disease, received intravenous injections of 45 units of bleomycin (Blenoxane), twice a week, for a total dose of 300 units. Fifteen rabbits received an equal volume of saline and served as controls. Treatment with bleomycin resulted in failure to thrive, weight loss, and 30% mortality from nonpulmonary causes, as indicated by the lack of respiratory distress or cyanosis, during or shortly after the injection period. The remainder of the animals were allowed to recover for 21 days following the last injection. At that time, no differences were found between the experimental and the control groups with respect to arterial blood gases, total lung capacity, compliance, and hydroxyproline content. Histologic examination of lung tissue revealed normal lung architecture. When exposed to 100% O2, bleomycin-treated rabbits developed arterial hypoxemia and died from respiratory failure at the same rate as the controls. It was concluded that pretreatment of healthy rabbits with 300 units of intravenous bleomycin did not result in the development of significant amounts of lung fibrosis or enhance the toxic effects of oxygen on the respiratory system.

Modification of pulmonary oxygen toxicity by bleomycin treatment.

The purpose of this study was to determine whether pretreatment of rabbits with bleomycin would modify their response to 100% O2 and, if so, to identify the mechanism of this action. A single intratracheal injection of bleomycin (5 U/kg) resulted in a transient decrease of the arterial Po2, its mean value (+/- SE) 7 days postinjection being 59 +/- 3 Torr. All animals were either killed or exposed to 100% O2 35 days postinjection. At this time, arterial Po2 had returned to its control level. On the other hand, lung hydroxyproline content had doubled and static compliance and the total lung capacity had decreased by 22 and 31%, respectively, indicating the existence of significant lung fibrosis. Furthermore, activities of catalase and superoxide dismutase in lung homogenates were higher than control and were further augmented by exposure to 100% O2 for 64 h. These biochemical changes may account, at least in part, for the mitigation of the toxic effects of hyperoxia, as shown by the delayed appearance of arterial hypoxemia, and the 50% increase in survival time when bleomycin injected rabbits were exposed to 100% O2 35 days postinjection.