On the pulmonary toxicity of oxygen: III. The induction of oxygen dependency by oxygen use

Oxygen is central to the development of neonatal lung injury. The increase in oxygen exposure of the neonatal lung during the onset of extrauterine air breathing is an order of magnitude, from a range of 10–12 to 110–120 Torr. The contributions of oxygen and the volume and pressure relationships of ventilatory support to lung injury are not easily distinguished in the clinical setting. Sequential changes in inspired air or 100% oxygen were studied in 536 newborn rabbits without ventilatory support. Bilateral cervical vagotomies (BCV) were performed at 24 h post natal to induce ventilatory distress which eventuates in hyaline membrane disease. The sequences applied yielded evidence for an induced state of oxygen dependency from oxygen use which was reflected in differences in survival and the extent of pulmonary injury. The median survival for animals kept in air throughout was 3 h. Oxygen before vagotomy or during the first 3 h afterwards extended the survival significantly but produced more extensive, more severe, and more rapid lung lesions. Returning animals to air after prior oxygen exposure reduced the number of survivors past 10 h and shortened the maximum survival in those groups. These features indicate the development of a dependency of the defense mechanisms on the availability of oxygen at the higher level for metabolic and possibly other aspects of the pulmonary and systemic response to injury, beyond the usual physiological need. Subset analysis revealed additive and latent effects of oxygen and demonstrated a remarkable rapidity in onset of severe lesions under some circumstances, illustrating the toxicity of oxygen per se.