• 2018-07
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  • 2020-01
  • 2020-02
  • Methacholine MCh is a bronchoconstrictive


    Methacholine (MCh) is a bronchoconstrictive agent that has been widely used in the diagnoses of airway narrowing and hyperresponsiveness (Jonasson et al., 2009). MCh induces muscle contractions by stimulating the muscarinic cholinergic receptors that are found in both the airways and the lung parenchyma (Barnes, 1993, Sly et al., 1995, Fisher et al., 2004). Muscarinic receptors located on the alveolar wall may be involved in the parenchymal response (Sly et al., 1995). The hypothesis of this study is that bronchial responsiveness during aerosolised MCh challenge should be amplified in mice with elastase-induced Cefotaxime sodium salt (0.3 and 0.6U elastase). This study also compared two thorax conditions: intact (closed thorax) and exposed lungs (opened thorax). The aim of this study was to analyse the bronchial responsiveness of the airways to a MCh challenge during elastase-induced emphysema in closed and opened thorax.
    Materials and methods
    Results The baseline respiratory mechanical data are presented in Table 1. The open or closed thorax conditions and the Sal, 0.3 and 0.6U groups were compared with two-way analysis of variance. The elastase-induce emphysema significantly decreased Raw (closed thorax), and the expected H decrease was found in the 0.6U group (p<0.05; closed and opened thorax). Additionally, η increased for the same group (closed thorax) relative to that of the Sal group. No changes in G were found. The MCh challenge is illustrated in Fig. 1, and all groups (in both the closed and opened thorax conditions) showed dose-dependent responses to aerosolised MCh (0 or vehicle, 50 and/or 100mg/mL) for all parameters except H in the 0.6U group (closed thorax condition), for which only 100mg/mL MCh resulted in a statistically significant difference relative to the H for the vehicle. The responses to 50mg/mL MCh in the control and elastase-induced emphysema groups did not significantly differ. However, the Raw response to 100mg/mL MCh in the 0.6U elastase-induced emphysema group (0.80±0.07cmH2Os/mL) was reduced when compared to that of the control group (1.51±0.33cmH2Os/mL; p<0.005) in the closed thorax condition, but no significant response was found in the opened thorax condition. G was significantly reduced in the 0.6U elastase-induced emphysema group (9.26±0.80cmH2O/mL) relative to that of the control group (15.34±1.54cmH2O/mL; p<0.005) in the closed thorax condition. However, in the opened thorax condition, the 0.3U group exhibited a significant increase in G (17.51±2.19cmH2O/mL) compared to control group (10.26±1.59cmH2O/mL; p<0.005). The H response to 100mg/mL MCh was significantly lower in the 0.6U elastase-induced emphysema group (25.40±2.60, closed thorax; 37.52±7.40cmH2O/mL, opened thorax) than in the control group (40.30±4.84; 56.27±3.63cmH2O/mL, respectively; p<0.005). The η response to the high dose of MCh was elevated in the 0.3U opened thorax group (0.42±0.05) compared to the control group (0.35±0.05). All elastase-induced emphysema groups showed significant reductions in the normal areas. Hyper-inflation was only significant increase in 0.6U group and Lm was only significant increase in 0.3U group than in control. However, the 0.6U elastase-induced emphysema group exhibited more alveolar collapse (Table 2) than the control group. The morphological changes in each group are shown in Fig. 2; note, in particular, the hyperinflated area in the 0.6U group.
    Discussion The present study revealed attenuated Raw (closed thorax), H and G (closed and opened thorax) responses in mice with elastase-induced emphysema after MCh challenge. These results may be associated with the collapsed and/or hyperinflated areas in the 0.6U mice with elastase-induced emphysema. These changes were studied with closed thorax to measure the mechanics of the intact respiratory system and in opened thorax to measure the mechanics without the influence of the rib Cefotaxime sodium salt cage and adjacent muscles. The attenuated response to MCh in the elastase group shown in the present study contributes new information about the behaviour of airways after MCh challenge and the respiratory system in COPD.