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1 Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany; Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany
2 Bloomberg School of Public Health, Division of Physiology, Johns Hopkins University, Baltimore, MD, USA
3 Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany
* To whom correspondence should be addressed. E-mail: thomasglaab{at}web.de.
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 non-sensitized BALB/c mice, dose-related increases in pulmonary resistance (RL) and dynamic compliance (Cdyn) to aerosolized methacholine (MCh) are reproducible over short and extended intervals without causing detectable cytological alterations in the broncho-alveolar lavage (BAL) 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 BAL fluids as well as significant pathological alterations in laryngotracheal histology, compared with non-sensitized 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 COPD, investigations of pulmonary pharmacology or more general investigations of the genetic determinants of lung function.
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