Moderate exposures to hyperoxia are becoming increasingly common in clinical medicine as advancing technology allows O2 to be more effectively delivered to nonintubated patients. The sensitivity of the lung to injury by a subchronic exposure to 60% O2 was investigated, using baboons and serial lobar biopsies. Because results obtained from different regions of the lung were compared, the alveolar architecture of different lung lobes of three controls was studied, with the use of electron microscopic morphometric analyses, to assess possible lobar differences in volume, surface, and numerical densities of cells and tissues. In animals exposed to 60% O2, the same techniques were used to assess specific tissue changes in the epithelial, interstitial, and endothelial compartments of the alveolar septa. All six lobes of the normal baboon lung were found to be identical with respect to alveolar architecture. Thus, for gases of low reactivity and given in high concentrations, such as O2, cross-comparisons between different lobes are appropriate. Exposure to 60% O2 was found to cause proliferation of alveolar type II epithelium, suggesting a low-grade, chronic epithelial injury. Animals allowed to recover for 8 wk in room air showed progressive changes in the alveolar interstitium, involving increases in both cells and matrix. Because sequential lobar resections were done, animals were exposed both to 60% O2 and to the effects of general anesthesia and thoracotomies. The exposure to 60% O2 for 2 wk in this experimental setting leads to an alveolar septal injury that includes a progressive interstitial fibrotic response.

Morphological, biochemical, and physiological studies were done on rats exposed to 60% O2 for 7 days. This exposure did not induce O2 tolerance but instead caused a significant decrease in survival time of animals subsequently exposed to pure O2. The activity of lung superoxide dismutases and glucose-6-phosphate dehydrogenase were unchanged after exposure to 60% O2. A decrease in lung compliance was suggested by changes in the total lung capacity and in the pressure-volume curves of excised lungs. Ventilation of these animals with large tidal excursion resulted in pulmonary edema. Morphometric analyses revealed a significant decrease in alveolar air volume and an increase in the number of alveolar macrophages. The most significant lesions involved the pulmonary vascular bed. The volume and thickness of the capillary endothelium was decreased. There were focal areas of pericapillary fluid accumulations, and a number of the smaller vessels had perivascular edema. These findings suggest that significant pulmonary injury occurs in rats exposed to 60% O2 and that the primary site of injury is the pulmonary capillary endothelium.

The total lung capacity (TLC) of rats was measured in vivo and was compared to the displacement volume of the lungs following intratracheal fixation with glutaraldehyde or formaldehyde solution. When glutaraldehyde was used the speed of infusion of the fixative was an important factor in the final degree of lung inflation achieved. With a low rate of fixative infusion and a final pressure of 20 cm of fixative the glutaraldehyde-fixed lungs inflated to 55% TLC. With a high initial flow of glutaraldehyde and a final pressure of 20 cm of fixative the lungs inflated to 84% TLC. Fixation of lungs inside the intact chest wall was found to result in a higher degree of inflation. With a reservoir height of 20 cm and a low rate of fixative infusion lungs fixed in situ reached 74% TLC, whereas lungs fixed in situ, but from animals that have been exsanguinated prior to fixation, inflated to only 58% TLC. This suggests that the volume of the blood in the lungs prior to infusion of glutaraldehyde influences the degree of inflation achieved. Formaldehyde-fixed lungs required 72 h to be completely fixed and they were inflated to 90% TLC when a reservoir height of 20 cm was used. Because of the slow rate of fixation using with formaldehyde solution the rate of infusion was found not to limit the degree of inflation that could be achieved.