Maturation as a factor in pulmonary oxygen toxicity: A preliminary report

Abstract

CLINICAL AND EXPERIMENTAL EVIDENCE has suggested that pulmonary oxygen toxicity is a major factor in the etiology of bronchopulmonary dysplasia? Continuous exposure of C57 black newborn mice to 100% oxygen for up to six weeks has produced necrotizing bronchiolitis, peribronchiolar fibrosis, emphysema and atelectasis, and interstitial fibrosis similar to the histopathology of bronchopulmonary dysplasia seen in human infants. 3 Biochemical analysis of these oxygen-exposed lungs has indicated that, in addition to the severe pathologic changes, there is a growth disturbance manifested by inhibition of lung DNA synthesis, diminished total lung DNA, and a decrease in the ratio of lung DNA to body weight? '~ Several investigators have noted the ability of certain immature animals to survive continuous exposure to high concentrations of oxygen longer than adult animals of the same species. 7 Newborn C57 black mice have survived continuous exposure to 100% oxygen for six weeks, whereas adult mice of the same strain similarly exposed all die within seven days. 3 This observation suggests that analysis of the period of change from the newborn survival response to continuous exposure to 100% oxygen to the adult response could provide further insight into the mechanisms responsible for the relative protection against pulmonary oxygen toxicity present in the newborn mouse. Further understanding of the mechanisms present in the immature lung which protect against pulmonary oxygen toxicity has great importance in management of both adult and neonatal respiratory disease. Identification of agents or drugs which can induce or augment this protection may provide a means to reduce the hazards of the use of supplemental oxygen in infants, children, and adults.