Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice.
BACKGROUND
Deep inspirations (DI) have bronchodilatory and bronchoprotective effects in healthy human subjects, but these effects appear to be absent in asthmatic lungs. We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation.


METHODS
Balb/c mice were sensitized to ovalbumin (OVA) and exposed to nebulized OVA for 1 week or 12 weeks. Control mice were challenged with PBS. Mice were randomly selected to receive DI, which were given twice during the minute before assessment of lung mechanics.


RESULTS
DI protected against bronchoconstriction of central airways in healthy mice and in mice with acute airway inflammation, but not when OVA-induced chronic inflammation was present. DI reduced lung resistance induced by methacholine from 3.8 +/- 0.3 to 2.8 +/- 0.1 cmH2O.s.mL-1 in healthy mice and 5.1 +/- 0.3 to 3.5 +/- 0.3 cmH2O.s.mL-1 in acute airway inflammation (both P < 0.001). In healthy mice, DI reduced the maximum decrease in lung compliance from 15.9 +/- 1.5% to 5.6 +/- 0.6% (P < 0.0001). This protective effect was even more pronounced in mice with chronic inflammation where DI attenuated maximum decrease in compliance from 44.1 +/- 6.6% to 14.3 +/- 1.3% (P < 0.001). DI largely prevented increased peripheral tissue damping (G) and tissue elastance (H) in both healthy (G and H both P < 0.0001) and chronic allergen-treated animals (G and H both P < 0.0001).


CONCLUSIONS
We have tested a mouse model of potential value for defining mechanisms and sites of action of DI in healthy and asthmatic human subjects. Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.
Jonasson
Sofia
S
Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden. sofia.jonasson@medsci.uu.se
Swedin
Linda
L
Lundqvist
Maria
M
Hedenstierna
Göran
G
Dahlén
Sven-Erik
SE
Hjoberg
Josephine
J
D000208:Acute Disease; D000403:Airway Resistance; D000818:Animals; D001991:Bronchitis / Q000276:immunology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002908:Chronic Disease; D004548:Elasticity; D007114:Immunization; D001239:Inhalation; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008170:Lung Compliance; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D015656:Respiratory Mechanics; D012137:Respiratory System / Q000503:physiopathology*
D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D010047:Ovalbumin