The elastase induced injury model has
The elastase-induced injury model has been shown to produce airspace enlargement, and increases in lung volume and compliance that are similar to those observed in human patients (Hantos et al., 2008, Hamakawa et al., 2011). Thus, this model, which has been used to study emphysema, should be adequate for a first-order evaluation of structure–function relationships during disease progression (Luthje et al., 2009, Snider, 2000, Kasahara et al., 2000). This method of emphysema induction yielded lengthy and progressive inflammation and remodelling of the lung tissue in addition to alveolar destruction. Elastase caused structural lung changes, including enlargement of the air spaces and Exendin-3 (9-39) amide destruction while simultaneously causing increases in the following: mean linear intercepts, fractions of collapsed and hyperinflated alveolar areas and alveolar-capillary membrane damage (Tomioka et al., 2002, Antunes and Rocco, 2011). In this study, two PPE doses were used to illustrate the magnitudes of functional changes after MCh challenge in Swiss mice; we used the same animal model and elastase-induced emphysema model used by Otto-Verberne et al. (1992). The present study has some connected points observed by Hantos et al. (2008) and Tasaka et al. (2010), but these authors did not focus on the MCh challenge and analyse the respiratory mechanics during open and closed thorax condition as seen in the present study. Hantos et al. (2008) used the same elastase-induced emphysema model changing transrespiratory pressure and measuring corresponding thoracic gas volume, elastance and airway resistance. These authors did not address MCh challenge in their study. Tasaka et al. (2010), using the elastase-induced emphysema, evaluated the inflammatory response in wild-type and IL-6-deficient (IL-6−/−) mice. Despite having measured the resistance airway responsiveness using lower doses of MCh, this was not explored by the authors. They emphasise the parameters at various time points of gene expression of MMP-12 and the importance of IL-6 in the development of PPE-induced lung inflammation, as well as subsequent tissue damage and regulations. No attention was given to respiratory mechanics and their work is consistent in inflammation in DPOC. Hantos et al. (2008) reported that the thoracic gas volume in mice increases by 50% in an elastase-induced emphysema model and that Raw was higher in the treatment group when compared to similar absolute lung volumes. In 2011, Hamakawa et al. showed the same pattern over 21 days (Hamakawa et al., 2011). However, after elastolytic injury, Raw at the same PEEP decrease and absolute lung volumes are higher in the induced-emphysema lungs. Consequently, the airways were pulled open more widely, which resulted in lower Raw. Similar changes have been observed in tight-skin mice (Ito et al., 2006), surfactant protein (SP)-D-deficient mice (Sly et al., 2003) and surfactant protein C/TNF-a – transgenic mice (Lundblad et al., 2005). Consistent with these results, a significant reduction in Raw in the closed thorax condition was demonstrated without MCh challenge for the elastase-induced emphysema (0.6U group) in this study. Together, these studies corroborate and increase the knowledge of the respiratory system, and the variations observed in the Raw indicate that more attention should be given to understanding the responsiveness of the airway when exposed to constrictor agents to create effective treatment approaches for COPD. Lungs are not perfectly homogeneous, even under baseline conditions. Instead, lungs exhibit substantial variation in the length of the pathway from the trachea to individual alveoli and exhibit additional regional variations in airway dimensions and tissue elasticity (Tomioka et al., 2002). The H of the elastase-induced emphysema group (0.6U) was significantly decreased compared with that of the Sal group in both the closed and opened thorax conditions, indicating deterioration of the elastic properties and stiffness of the tissue (Ito et al., 2005, Hamakawa et al., 2011).