Repair of chronic hyperoxic lung injury: changes in lung ultrastructure and matrix

We studied changes in lung ultrastructure, fibronectin, and collagen during repair of chronic hyperoxic lung injury induced by exposure of rats to 85% oxygen for 14 days. Morphologically, the most persistent changes were in the alveolar interstitium. After 28 days of repair, the extracellular matrix volume was still twofold normal. Total interstitial cell numbers also remained high and interstitial myofibroblast number actually doubled between Days 7 and 14. These changes contrast markedly with repair of acute lung injury induced by 100% oxygen (Thet et al. (1986) Exp. Lung Res. 11, 209-228) in which matrix volume and interstitial myofibroblast number increased initially but then returned to normal. Biochemically, tissue-associated fibronectin was high initially and peaked at 3 days before slowly declining. Tissue collagen content began to increase after the peak in fibronectin content and was over 150% of controls at 28 days; this correlated with an increase in visible collagen fibers. We conclude that changes in lung morphology and matrix after chronic hyperoxic lung injury are more persistent than after acute hyperoxic lung injury and result in a greater degree of chronic interstitial fibrosis.