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

Abstract

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) (C5o-70) and that between 80 and 100% TLC (C8o-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. Cao-ioo 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. pulmonary emphysema ; mean linear intercept ; lung compliance ; alveolar surface area

Pulmonary haemodynamics in awake rats following treatment with endotracheal pancreatic elastase

“…From these results, we concluded that 80 U·100g -1 BW is optimal for a rat emphysema model produced by a single intratracheal instillation of porcine pancreatic elastase. With 80 U, mean linear intercept was 98 µm, 1.4 times that of the control value, 72 µm [10]. This degree of widening of alveolar space corresponds to human emphysema ranging from mild to relatively severe [23].…”

“…In earlier work, we tested dose dependency of lung pressure-volume curve and morphometry using porcine pancreatic elastase ranging from 20-100 U·100g -1 BW in rats [10]. The pressure-volume curve at 100 U was more to the right and downward than at 80 U and, in addition, animal mortality shortly after instillation was higher.…”

“…To the emphysema group (Group-EL), a single endotracheal instillation of porcine pancreatic elastase (US Biochemical Co., Cleveland, USA) was administered (80 U in 0.2 ml saline·100 g -1 BW) [10]. Pancreatic elastase was dissolved in saline immediately before use.…”