title: Bronchoprotective effect of simulated deep inspirations in tracheal smooth muscle.
abstract: Deep inspirations (DIs) taken before an inhaled challenge with a spasmogen limit airway responsiveness in nonasthmatic subjects. This phenomenon is called bronchoprotection and is severely impaired in asthmatic subjects. The ability of DIs to prevent a decrease in forced expiratory volume in 1 s (FEV1) was initially attributed to inhibition of airway narrowing. However, DIs taken before methacholine challenge limit airway responsiveness only when a test of lung function requiring a DI is used (FEV1). Therefore, it has been suggested that prior DIs enhance the compliance of the airways or airway smooth muscle (ASM). This would increase the strain the airway wall undergoes during the subsequent DI, which is part of the FEV1 maneuver. To investigate this phenomenon, we used ovine tracheal smooth muscle strips that were subjected to shortening elicited by acetylcholine with or without prior strain mimicking two DIs. The compliance of the shortened strip was then measured in response to a stress mimicking one DI. Our results show that the presence of "DIs" before acetylcholine-induced shortening resulted in 11% greater relengthening in response to the third DI, compared with the prior DIs. This effect, although small, is shown to be potentially important for the reopening of closed airways. The effect of prior DIs was abolished by the adaptation of ASM to either shorter or longer lengths or to a low baseline tone. These results suggest that DIs confer bronchoprotection because they increase the compliance of ASM, which, consequently, promotes greater strain from subsequent DI and fosters the reopening of closed airways.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Center for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada chris.pascoe@hli.ubc.ca.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pascoe
authors.affiliation: Department of Mathematics, University of Auckland, Auckland, New Zealand;
authors.forename: Graham M
authors.initials: GM
authors.lastname: Donovan
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada; and.
authors.forename: Ynuk
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Center for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Chun Y
authors.initials: CY
authors.lastname: Seow
authors.affiliation: Department of Medicine, Respiratory Division, University of British Columbia, Vancouver, British Columbia, Canada; Center for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000222:Adaptation, Physiological; D000403:Airway Resistance; D000818:Animals; D001696:Biomechanical Phenomena; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D005541:Forced Expiratory Volume; D066298:In Vitro Techniques; D001239:Inhalation / Q000187:drug effects; D008170:Lung Compliance; D008954:Models, Biological; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D012756:Sheep; D013314:Stress, Mechanical; D013997:Time Factors; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
chemical_list: D016085:Bronchoconstrictor Agents; D000109:Acetylcholine
keywords: airway hyperresponsiveness; asthma; mathematical modeling; muscle mechanics