Abstract:This study was undertaken to determine whether a smaller lung volume or a stiffer lung tissue accounts for the greater lung elastance of C57BL/6 than BALB/c mice. The mechanical properties of the respiratory system and lung volumes were measured with the flexiVent and compared between male C57BL/6 and BALB/c mice (n = 9). The size of the excised lung was also measured by volume liquid displacement. One lobe was then subjected to sinusoidal strains in vitro to directly assess the mechanical properties of the lu… Show more
“…BALB/c mice exhibited a greater airway distensibility than C57BL/6 mice. This is consistent with the stiffer lung of C57BL/6 versus BALB/c mice [ 17 ]. There was also a significant interaction between sex and mouse strain.…”
Section: Discussionsupporting
confidence: 85%
“…The pressure range was different between mouse strains because preliminary results demonstrated that the approximately linear change in Newtonian resistance ( R N ) caused by inflating pressure occurs over a smaller range in BALB/c compared to C57BL/6 mice. This is consistent with the stiffer lung of C57BL/6 compared to BALB/c mice [ 17 ]. Fig.…”
Section: Methodssupporting
confidence: 84%
“…Mice were anesthetized and put under general analgesia using ketamine (100 mg/kg) and xylazine (10 mg/kg), and then tracheotomized and connected to the flexiVent (FX Module 2, SCIREQ, Montreal, QC, Canada) as previously described [ 17 , 18 ]. They were ventilated mechanically at a tidal volume of 10 mL/kg with an inspiratory-to-expiratory time ratio of 2:3 at a breathing frequency of 150 breaths/min and with a positive end-expiratory pressure of 3 cmH 2 O.…”
Airway distensibility is defined as the ease whereby airways are dilating in response to inflating lung pressure. If measured swiftly and accurately, airway distensibility would be a useful readout to parse the various elements contributing to airway wall stiffening, such as smooth muscle contraction, surface tension, and airway remodeling. The goal of the present study was to develop a method for measuring airway distensibility in mice. Lungs of BALB/c and C57BL/6 mice from either sex were subjected to stepwise changes in pressure. At each pressure step, an oscillometric perturbation was used to measure the impedance spectrum, on which the constant-phase model was fitted to deduce a surrogate for airway caliber called Newtonian conductance (GN). The change in GN over the change in pressure was subsequently used as an index of airway distensibility. An additional group of mice was infused with methacholine to confirm that smooth muscle contraction changes airway distensibility. GN increased with increasing steps in pressure, suggesting that the extent to which this occurs can be used as an index of airway distensibility. Airway distensibility was greater in BALB/c than C57BL/6 mice, and its variation by sex was mouse strain dependent, being greater in female than male in BALB/c mice with an inverse trend in C57BL/6 mice. Airway distensibility was also decreased by methacholine. This novel method swiftly measures airway distensibility in mice. Airway distensibility was also shown to vary with sex and mouse strain and to be sensitive to the contraction of smooth muscle.
“…BALB/c mice exhibited a greater airway distensibility than C57BL/6 mice. This is consistent with the stiffer lung of C57BL/6 versus BALB/c mice [ 17 ]. There was also a significant interaction between sex and mouse strain.…”
Section: Discussionsupporting
confidence: 85%
“…The pressure range was different between mouse strains because preliminary results demonstrated that the approximately linear change in Newtonian resistance ( R N ) caused by inflating pressure occurs over a smaller range in BALB/c compared to C57BL/6 mice. This is consistent with the stiffer lung of C57BL/6 compared to BALB/c mice [ 17 ]. Fig.…”
Section: Methodssupporting
confidence: 84%
“…Mice were anesthetized and put under general analgesia using ketamine (100 mg/kg) and xylazine (10 mg/kg), and then tracheotomized and connected to the flexiVent (FX Module 2, SCIREQ, Montreal, QC, Canada) as previously described [ 17 , 18 ]. They were ventilated mechanically at a tidal volume of 10 mL/kg with an inspiratory-to-expiratory time ratio of 2:3 at a breathing frequency of 150 breaths/min and with a positive end-expiratory pressure of 3 cmH 2 O.…”
Airway distensibility is defined as the ease whereby airways are dilating in response to inflating lung pressure. If measured swiftly and accurately, airway distensibility would be a useful readout to parse the various elements contributing to airway wall stiffening, such as smooth muscle contraction, surface tension, and airway remodeling. The goal of the present study was to develop a method for measuring airway distensibility in mice. Lungs of BALB/c and C57BL/6 mice from either sex were subjected to stepwise changes in pressure. At each pressure step, an oscillometric perturbation was used to measure the impedance spectrum, on which the constant-phase model was fitted to deduce a surrogate for airway caliber called Newtonian conductance (GN). The change in GN over the change in pressure was subsequently used as an index of airway distensibility. An additional group of mice was infused with methacholine to confirm that smooth muscle contraction changes airway distensibility. GN increased with increasing steps in pressure, suggesting that the extent to which this occurs can be used as an index of airway distensibility. Airway distensibility was greater in BALB/c than C57BL/6 mice, and its variation by sex was mouse strain dependent, being greater in female than male in BALB/c mice with an inverse trend in C57BL/6 mice. Airway distensibility was also decreased by methacholine. This novel method swiftly measures airway distensibility in mice. Airway distensibility was also shown to vary with sex and mouse strain and to be sensitive to the contraction of smooth muscle.
Purpose
Air trapping, often attested in humans by elevated residual volume (RV) and ratio of RV on total lung capacity (RV/TLC), is frequently observed in asthma. Confirming these alterations in experimental asthma would be important for translational purposes. Herein, lung volumes were investigated in a mouse model of pulmonary allergic inflammation.
Methods
Eight- to 10-week-old male C57BL/6 and BALB/c mice were exposed once daily to intranasal house dust mite (HDM) for 10 consecutive days. All readouts were measured 24 h after the last exposure. Lung volumes were assessed with the flexiVent using a new automated method consisting of degassing the lungs followed by a full-range pressure–volume maneuver. The weight and the volume of the lungs were also measured ex vivo and a lobe was further processed for histological analyses.
Results
HDM exposure led to tissue infiltration with inflammatory cells, goblet cell hyperplasia, thickening of the airway epithelium, and elevated ex vivo lung weight and volume. It also decreased TLC and vital capacity but without affecting RV and RV/TLC. These observations were similar between the two mouse strains.
Conclusion
Alterations of lung volumes in a murine model of pulmonary allergic inflammation are inconsistent with observations made in human asthma. These discrepancies reflect the different means whereby lung volumes are measured between species. The invasive method used herein enables RV to be measured more precisely and without the confounding effect of air trapping, suggesting that changes in RV and RV/TLC using this method in mice should be interpreted differently than in humans.
Asthma is a chronic respiratory disease of global importance. Mouse models of allergic asthma have been instrumental in advancing research and novel therapeutic strategies for patients. The application of relevant allergens and physiological routes of exposure in such models has led to valuable insights into the complexities of asthma onset and development as well as key disease mechanisms. Furthermore, environmental microbial exposures and infections have been shown to play a fundamental part in asthma pathogenesis and alter disease outcome. In this review, we delve into physiological mouse models of allergic asthma and explore literature reports on most significant interplays between microbial infections and asthma development with relevance to human disease.
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