View Abstract

A1233 - Repeated Bronchoconstrictions Do Not Alter Respiratory Mechanics in Mice
Author Block: S. Mailhot-Larouche, M. Gazzola, K. Lortie, C. Henry, Y. Bossé; Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval, Quebec, QC, Canada.
RATIONALE: A new paradigm in asthma implies that bronchoconstriction contributes to airway wall remodeling in an inflammatory context. However, the direct effect on repeated bronchoconstrictions on airway remodeling and other features of asthma in a context devoid of inflammation has never been investigated systematically in vivo. In this study, we set out to determine whether repeated bronchoconstrictions elicited by methacholine (MCh) lead to some features of asthma in naïve mice. METHODS: BALB/c mice were exposed to either aerosolized saline or MCh at 7 mg/ml for 30 minutes every other day during 6 weeks. Specific airway resistance was measured using the double-chamber plethysmograph both before and after each exposure in order to confirm bronchoconstriction on every tested day in MCh-exposed mice, as well as to determine whether the magnitude of the induced bronchoconstriction changes over the course of the 6 weeks. The remaining experiments were all performed at the end of the protocol, 48 hours after the last exposure. In half of the mice from both the saline and MCh-exposed groups, respiratory mechanics was measured at baseline and in response to escalading doses of MCh using the flexiVent. The other half of the mice in each group were euthanized to collect the tracheas and the lungs. The tracheas were mounted in organ’s baths to test their contractile capacity in response to different spasmogens. The lungs were processed for histology in order to quantify the amount of smooth muscle within the airway wall, the content of collagen within the lung and the number goblet cells in the epithelium. RESULTS: The response to MCh did not change over the course of the protocol. After 6 weeks, respiratory mechanics at baseline and in response to escalading doses of MCh was identical between the groups. The ex vivo responses of excised tracheal segments to MCh and KCl were also not affected by repeated in vivo bronchoconstriction. Histological analyses showed no differences in the area occupied by the smooth muscle within the airway wall and in the content of collagen within the lung. However, the number of goblet cells was significantly elevated in mice that were repeatedly bronchoconstricted in vivo. More experiments are required to confirm these findings. CONCLUSION: Despite altering some features of the airway wall, repeated bronchoconstrictions in mice affect neither the respiratory mechanics at baseline and in response to MCh, nor the ex vivo contractility of airway smooth muscle.