title: Acute Lung Injury Causes Asynchronous Alveolar Ventilation That Can Be Corrected by Individual Sighs.
abstract: BACKGROUND
  Improved ventilation strategies have been the mainstay for reducing mortality in acute respiratory distress syndrome. Their unique clinical effectiveness is, however, unmatched by our understanding of the underlying mechanobiology, and their impact on alveolar dynamics and gas exchange remains largely speculative.
  
  
  OBJECTIVE
  To assess changes in alveolar dynamics and associated effects on local gas exchange in experimental models of acute lung injury (ALI) and their responsiveness to sighs.
  
  
  METHODS
  Alveolar dynamics and local gas exchange were studied in vivo by darkfield microscopy and multispectral oximetry in experimental murine models of ALI induced by hydrochloric acid, Tween instillation, or in antibody-mediated transfusion-related ALI.
  
  
  RESULTS
  Independent of injury mode, ALI resulted in asynchronous alveolar ventilation characteristic of alveolar pendelluft, which either spontaneously resolved or progressed to a complete cessation or even inversion of alveolar ventilation. The functional relevance of the latter phenomena was evident as impaired blood oxygenation in juxtaposed lung capillaries. Individual sighs (2 × 10 s at inspiratory plateau pressure of 30 cm H2O) largely restored normal alveolar dynamics and gas exchange in acid-induced ALI, yet not in Tween-induced surfactant depletion.
  
  
  CONCLUSIONS
  We describe for the first time in detail the different forms and temporal sequence of impaired alveolar dynamics in the acutely injured lung and report the first direct visualization of alveolar pendelluft. Moreover, we identify individual sighs as an effective strategy to restore intact alveolar ventilation by a mechanism independent of alveolar collapse and reopening.
authors.affiliation: 1 Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Arata
authors.initials: A
authors.lastname: Tabuchi
authors.affiliation: 2 Institute of Physiology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Hannah T
authors.initials: HT
authors.lastname: Nickles
authors.affiliation: 1 Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Kim
authors.affiliation: 1 Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.|3 Department of Pharmacology.|4 Department of Medicine.|5 Department of Laboratory Medicine and Pathobiology.
authors.forename: John W
authors.initials: JW
authors.lastname: Semple
authors.affiliation: 6 Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Medical Faculty of the Technical University, Dresden, Germany; and.
authors.forename: Edmund
authors.initials: E
authors.lastname: Koch
authors.affiliation: 1 Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.|7 Interdepartmental Division of Critical Care Medicine.
authors.forename: Laurent
authors.initials: L
authors.lastname: Brochard
authors.affiliation: 1 Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.|7 Interdepartmental Division of Critical Care Medicine.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.affiliation: 2 Institute of Physiology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Axel R
authors.initials: AR
authors.lastname: Pries
authors.affiliation: 1 Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.|2 Institute of Physiology, Charité-Universitätsmedizin, Berlin, Germany.|8 Department of Surgery, and.|9 Department of Physiology, University of Toronto, Toronto, Ontario, Canada.|10 German Heart Institute, Berlin, Germany.
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Kuebler
mesh_terms: D055371:Acute Lung Injury / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D045853:Exhalation / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010092:Oximetry; D011650:Pulmonary Alveoli / Q000503:physiopathology*; D015656:Respiratory Mechanics / Q000502:physiology*
keywords: intravital microscopy; multispectral oximetry; pendelluft