title: Mechanical ventilation causes airway distension with proinflammatory sequelae in mice.
abstract: The pathogenesis of ventilator-induced lung injury has predominantly been attributed to overdistension or mechanical opening and collapse of alveoli, whereas mechanical strain on the airways is rarely taken into consideration. Here, we hypothesized that mechanical ventilation may cause significant airway distension, which may contribute to the pathological features of ventilator-induced lung injury. C57BL/6J mice were anesthetized and mechanically ventilated at tidal volumes of 6, 10, or 15 ml/kg body wt. Mice were imaged by flat-panel volume computer tomography, and central airways were segmented and rendered in 3D for quantitative assessment of airway distension. Alveolar distension was imaged by intravital microscopy. Functional dead space was analyzed in vivo, and proinflammatory cytokine release was analyzed in isolated, ventilated tracheae. CT scans revealed a reversible, up to 2.5-fold increase in upper airway volume during mechanical ventilation compared with spontaneous breathing. Airway distension was most pronounced in main bronchi, which showed the largest volumes at tidal volumes of 10 ml/kg body wt. Conversely, airway distension in segmental bronchi and functional dead space increased almost linearly, and alveolar distension increased even disproportionately with higher tidal volumes. In isolated tracheae, mechanical ventilation stimulated the release of the early-response cytokines TNF-α and IL-1β. Mechanical ventilation causes a rapid, pronounced, and reversible distension of upper airways in mice that is associated with an increase in functional dead space. Upper airway distension is most pronounced at moderate tidal volumes, whereas higher tidal volumes redistribute preferentially to the alveolar compartment. Airway distension triggers proinflammatory responses and may thus contribute relevantly to ventilator-induced pathologies.
authors.affiliation: Institute of Physiology, Charité, Universitaetsmedizin Berlin, Germany;
authors.forename: Hannah T
authors.initials: HT
authors.lastname: Nickles
authors.affiliation: German Cancer Research Center Heidelberg, Heidelberg, Germany;
authors.forename: Migle
authors.initials: M
authors.lastname: Sumkauskaite
authors.affiliation: German Cancer Research Center Heidelberg, Heidelberg, Germany;
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: German Cancer Research Center Heidelberg, Heidelberg, Germany;
authors.forename: Ingmar
authors.initials: I
authors.lastname: Wegner
authors.affiliation: German Cancer Research Center Heidelberg, Heidelberg, Germany; Chest Clinic Heidelberg, Heidelberg, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Puderbach
authors.affiliation: Institute of Physiology, Charité, Universitaetsmedizin Berlin, Germany; Departments of Surgery and Physiology, University of Toronto, Toronto, Ontario, Canada; The Keenan Research Center for Biomedical Science of St. Michael's, Toronto, Ontario, Canada kueblerw@smh.ca.
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Kuebler
mesh_terms: D000818:Animals; D019296:Capnography; D007249:Inflammation; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000473:pathology* / Q000503:physiopathology; D012121:Respiration, Artificial / Q000009:adverse effects*; D013314:Stress, Mechanical; D013990:Tidal Volume / Q000502:physiology*; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D055397:Ventilator-Induced Lung Injury / Q000473:pathology*
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha
keywords: airways; inflammation; mechanical ventilation; strain; ventilator-induced lung injury