Lung growth in rats subsequent to administration of intraperitoneal elastase during the first 4 weeks of life

Male rats received intraperitoneal injections of porcine pancreatic elastase twice weekly during the first 4 weeks of life. Saline-injected male rats served as controls. After a 4-week recovery period, the rats were sacrificed, and the excised lungs were studied using saline- and air-filled volume-pressure curves, morphology, and biochemistry. Both air- and saline-filled volume-pressure curves showed loss of elastic recoil in the elastase-treated animals. In elastase-treated animals the mean linear intercept was increased, the numbers of alveoli per unit area, per unit volume, and per lung decreased, and alveolar surface area decreased. These animals also showed a disproportionate increase of alveolar duct air at the expense of the proportion of alveolar air. Morphometric differences between the elastase-treated animals and the controls were somewhat smaller in this experiment than in a previous one in which the animals were sacrificed immediately after 4 weeks of intraperitoneal elastase. We attribute this difference to alveolar multiplication between 4 and 8 weeks of age. However, evidence is presented that these alveoli were abnormal. Loss of recoil properties was more evident after the 4-week recovery period than at the termination of elastase administration, suggesting that the newly formed alveoli were functionally abnormal. Collagen content was increased in the elastase group, but elastin was significantly decreased. This may be a good elastase model for assessing the hypothesis that lungs minimally damaged in infancy may have an increased susceptibility to environmental damage in later life.