Restrained whole body plethysmography for measure of strain-specific and allergen-induced airway responsiveness in conscious mice

Abstract

The mouse is the most extensively studied animal species in respiratory research, yet the technologies available to assess airway function in conscious mice are not universally accepted. We hypothesized that whole body plethysmography employing noninvasive restraint (RWBP) could be used to quantify specific airway resistance (sRaw-RWBP) and airway responsiveness in conscious mice. Methacholine responses were compared using sRaw-RWBP vs. airway resistance by the forced oscillation technique (Raw-FOT) in groups of C57, A/J, and BALB/c mice. sRaw-RWBP was also compared with sRaw derived from double chamber plethysmography (sRaw-DCP) in BALB/c. Finally, airway responsiveness following allergen challenge in BALB/c was measured using RWBP. sRaw-RWBP in C57, A/J, and BALB/c mice was 0.51 +/- 0.03, 0.68 +/- 0.03, and 0.63 +/- 0.05 cm/s, respectively. sRaw derived from Raw-FOT and functional residual capacity (Raw*functional residual capacity) was 0.095 cm/s, approximately one-fifth of sRaw-RWBP in C57 mice. The intra- and interanimal coefficients of variations were similar between sRaw-RWBP (6.8 and 20.1%) and Raw-FOT (3.4 and 20.1%, respectively). The order of airway responsiveness employing sRaw-RWBP was AJ > BALBc > C57 and for Raw-FOT was AJ > BALB/c = C57. There was no difference between the airway responsiveness assessed by RWBP vs. DCP; however, baseline sRaw-RWBP was significantly lower than sRaw-DCP. Allergen challenge caused a progressive decrease in the provocative concentration of methacholine that increased sRaw to 175% postsaline values based on sRaw-RWBP. In conclusion, the technique of RWBP was rapid, reproducible, and easy to perform. Airway responsiveness measured using RWBP, DCP, and FOT was equivalent. Allergen responses could be followed longitudinally, which may provide greater insight into the pathogenesis of chronic airway disease.

Detrimental effects of albuterol on airway responsiveness requires airway inflammation and is independent of β-receptor affinity in murine models of asthma

“…We studied this in three different strains of mice previously shown to have different degrees of responsiveness to methacholine. Other studies have shown the order of sensitivity to methacholine to be A/J > Balb/C > C57Bl/6 [25-27], with A/J often considered to be genetically hyperresponsive. We found that naïve mice of all of these strains were unaffected by either (RS)-, (S)- or (R)- albuterol treatment to a significant degree (Figures 4 and 5).…”

Structure-Function Analysis of CCL28 in the Development of Post-viral Asthma

“…Airway Hyper-responsiveness-A dose-response curve to aerosolized methacholine (0, 10, 20, 40, 80, and 160 mg/ml in PBS) using two-chamber plethysmography (Buxco) in conscious mice was performed on the days indicated (20). Airway hyper-responsiveness was determined as specific airway resistance (sRaw) and compliance (sGaw) measured with each dose of methacholine and reported as the percent change from baseline.…”

Mitochondrial Structural Changes and Dysfunction Are Associated with Experimental Allergic Asthma

“…Also, restrained DCP technique has been performed, because this technique is soundly based on the first principles of physics of the lung similar to invasive techniques and allows nonterminal measurements. It has recently been shown that there was an excellent correlation between sRaw-DCP method and airway resistance by the forced oscillation technique (19). These measurements were estimated on day 33 for all mice.…”