Repetitive measurements of pulmonary mechanics to inhaled cholinergic challenge in spontaneously breathing mice

Thomas Glaab, Wayne Mitzner, Armin Braun, Heinrich Ernst, Regina Korolewitz, Jens M. Hohlfeld, Norbert Krug, Heinz G. Hoymann

Research output: Contribution to journalArticlepeer-review

Abstract

Precise and repeatable measurements of pulmonary function in intact mice are becoming increasingly important for experimental investigations on various respiratory disorders including asthma. Here, we present validation of a novel in vivo method that, for the first time, combines direct and repetitive recordings of standard pulmonary mechanics with cholinergic aerosol challenges in anesthetized, orotracheally intubated, spontaneously breathing mice. We demonstrate that, in several groups of nonsensitized BALB/c mice, dose-related increases in pulmonary resistance and dynamic compliance to aerosolized methacholine are reproducible over short and extended intervals without causing detectable cytological alterations in the bronchoalveolar lavage or relevant histological changes in the proximal trachea and larynx regardless of the number of orotracheal intubations. Moreover, as further validation, we confirm that allergic mice, sensitized and challenged with Aspergillus fumigatus, were significantly more responsive to cholinergic challenge (P < 0.01) and exhibited marked eosinophilia and lymphocytosis in bronchoalveolar lavage fluids as well as significant pathological alterations in laryngotracheal histology compared with nonsensitized mice. We suggest that this approach will provide useful and necessary information on pulmonary mechanics in studies of various respiratory disorders in mice, including experimental models of asthma and chronic obstructive pulmonary disorder, investigations of pulmonary pharmacology, or more general investigations of the genetic determinants of lung function.

Original languageEnglish (US)
Pages (from-to)1104-1111
Number of pages8
JournalJournal of applied physiology
Volume97
Issue number3
DOIs
StatePublished - Sep 2004

Keywords

  • Allergy
  • Bronchial asthma
  • Experimental animal models
  • Pulmonary function test

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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