Dose dependency of intratracheal elastase-induced changes in pressure volume curve and morphometry in rat lungs

We studied the dose-dependency of the lung pressure-volume curve (n = 37) and morphometry (n = 30) with intratracheally administered elastase. Four weeks after elastase was instilled at dosages of 20 (EL-20), 40, 80, and 100 U/100 g wt., chord compliance between 50 and 70% of total lung capacity (TLC) (C50-70) and that between 80 and 100% TLC (C80-100) were measured. After a significant initial reduction, the weight of the EL-80 group recovered to the control level, whereas the weight curve of the EL-100 significantly decreased below that of the EL-80. Lung volumes of all the elastase-treated groups were significantly larger than those of control. Air-filled lung volumes monotonously increased when the elastase dose was increased from 20 to 80 U/100 g wt. In contrast lung volume of the EL-100 was significantly lower than that of the EL-80. On the other hand, liquid-filled lung volumes monotonously increased from 20 to 100 U/100 g wt. C80-100 was significantly smaller in the EL-100 than in the EL-80. The mean linear intercept increased and alveolar surface area decreased monotonously over the dose range tested. We conclude that there is a critical dose of elastase below which lung volume is increased and above which the increase is suppressed when elastase is administered intratracheally to Wistar rats.