Review article
Developmental aspects of experimental pulmonary oxygen toxicity

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Abstract

One of the more fascinating aspects of in vivo research on pulmonary O2 toxicity is the striking difference in the response of the neonatal versus the adult animal to hyperoxia. In general, neonatal animals are much more resistant to the characteristic O2-induced lung pathology seen in adult animals in hyperoxia. Neonatal animals are also able to rapidly mount a protective lung biochemical response to high O2 exposure [increased pulmonary antioxidant enzyme (AOE) activities], and adaptive response which adult animals have lost the ability to manifest in >95% O2. This review focuses on the disparate AOE responses of the neonatal versus adult animal in hyperoxia. It also explores other possible explanations for the striking O2 tolerance of young versus adult animals, including comparative O2 free radical production rates, inflammatory cell responses, lung lipid composition repair capabilities, etc. Discussions also centers on a less well studied toxic complication associated with hyperoxic exposure in the neonatal animal, i.e., the marked inhibitory effect of O2 exposure on normal lung growth and development of an alveolarized lung with an expanded respiratory exchange surface area. Finally, effective experimental means of protecting adult (and neonatal) animals from pulmonary O2 toxicity are reviewed. A closing section considers the enlightening new information that molecular biology has revealed about the regulation of AOE gene expression during normal development and under conditions of hyperoxidant challenge.

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    ∗

    Lee Frank, M.D., Ph.D., is Professor of Medicine and Professor of Pediatrics at the University of Miami School of Medicine. He received his M.D. degree from the University of Chicago in 1972, did his residency training in Pediatrics at the University of Iowa Hospitals, and received his Ph.D. in Pharmacology/Toxicology from the University of Iowa in 1978. He has been involved in full-time pulmonary research at the University of Miami School of Medicine since 1978 with a special interest in age-related pulmonary O2 toxicity and means of protection against O2 toxicity in experimental animals and in O2-requiring premature newborns prone to develop chronic lung disease (bronchopulmonary dysplasia). His other special interest is in helping to develop the research potential of Research Fellows/Trainees in the Medicine/Pediatrics Research Center at Miami.

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