title: 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.
authors.affiliation: Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA 01536, USA.
authors.forename: Jennifer L S
authors.initials: JL
authors.lastname: Lofgren
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Mazan
authors.forename: Edward P
authors.initials: EP
authors.lastname: Ingenito
authors.forename: Kara
authors.initials: K
authors.lastname: Lascola
authors.forename: Molly
authors.initials: M
authors.lastname: Seavey
authors.forename: Ashley
authors.initials: A
authors.lastname: Walsh
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hoffman
mesh_terms: D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D003243:Consciousness / Q000502:physiology; D005260:Female; D005540:Forced Expiratory Flow Rates / Q000502:physiology; D005541:Forced Expiratory Volume / Q000187:drug effects; D016210:Methacholine Chloride / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009991:Oscillometry; D010993:Plethysmography, Whole Body / Q000295:instrumentation / Q000379:methods*; D012149:Restraint, Physical; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride