title: Neural control of ventilation prevents both over-distension and de-recruitment of experimentally injured lungs.
abstract: Endogenous pulmonary reflexes may protect the lungs during mechanical ventilation. We aimed to assess integration of continuous neurally adjusted ventilatory assist (cNAVA), delivering assist in proportion to diaphragm's electrical activity during inspiration and expiration, and Hering-Breuer inflation and deflation reflexes on lung recruitment, distension, and aeration before and after acute lung injury (ALI).
  
  
  
  In 7 anesthetised rabbits with bilateral pneumothoraces, we identified adequate cNAVA level (cNAVAAL) at the plateau in peak ventilator pressure during titration procedures before (healthy lungs with endotracheal tube, [HLETT]) and after ALI (endotracheal tube [ALIETT] and during non-invasive ventilation [ALINIV]). Following titration, cNAVAALwas maintained for 5min. In 2 rabbits, procedures were repeated after vagotomy (ALIETT+VAG). In 3 rabbits delivery of assist was temporarily modulated to provide assist on inspiration only. Computed tomography was performed before intubation, before ALI, during cNAVA titration, and after maintenance at cNAVAAL.
  
  
  
  During ALIETTand ALINIV, normally aerated lung-regions doubled and poorly aerated lung-regions decreased to less than a third (p<0.05) compared to HLETT; no over-distension was observed. Tidal volumes were<5ml/kg throughout. Removing assist during expiration resulted in lung de-recruitment during ALIETT, but not during ALINIV. During ALIETT+VAGthe expiratory portion of EAdi disappeared, resulting in cyclic lung collapse and recruitment.
  
  
  
  When using cNAVA in ALI, vagally mediated reflexes regulated lung recruitment preventing both lung over-distension and atelectasis. During non-invasive cNAVA the upper airway muscles play a role in preventing atelectasis. Future studies should be performed to compare these findings with conventional lung-protective approaches.
authors.affiliation: Interdepartmental Division of Critical Care Medicine, University of Toronto, Department of Critical Care Medicine, St. Michael's Hospital, Toronto, Canada; Department of Intensive Care Medicine, Cantonal Hospital of Lucerne, Switzerland. Electronic address: lukas.brander@luks.ch.
authors.forename: Lukas
authors.initials: L
authors.lastname: Brander
authors.affiliation: Interdepartmental Division of Critical Care Medicine, University of Toronto, Department of Critical Care Medicine, St. Michael's Hospital, Toronto, Canada; Department of Anaesthesiology, Emergency and Critical Care Medicine, University of Göttingen, Germany.
authors.forename: Onnen
authors.initials: O
authors.lastname: Moerer
authors.affiliation: Department of Medical Sciences, Clinical Physiology, University of Uppsala, Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Hedenstierna
authors.affiliation: Department of Pediatrics, University of Toronto, Toronto, Canada; Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada; Institute for Biomedical Engineering and Science Technology (iBEST) at Ryerson University and St. Michael's Hospital, Toronto, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Beck
authors.affiliation: Department of Intensive Care Medicine, Bern University Hospital - Inselspital, and University of Bern, Switzerland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Takala
authors.affiliation: Interdepartmental Division of Critical Care Medicine, University of Toronto, Department of Critical Care Medicine, St. Michael's Hospital, Toronto, Canada; Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.affiliation: Interdepartmental Division of Critical Care Medicine, University of Toronto, Department of Critical Care Medicine, St. Michael's Hospital, Toronto, Canada; Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada; Institute for Biomedical Engineering and Science Technology (iBEST) at Ryerson University and St. Michael's Hospital, Toronto, Canada.
authors.forename: Christer
authors.initials: C
authors.lastname: Sinderby
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D045853:Exhalation / Q000502:physiology*; D059725:Interactive Ventilatory Support / Q000379:methods*; D055370:Lung Injury / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D063087:Noninvasive Ventilation; D011817:Rabbits; D012121:Respiration, Artificial / Q000379:methods*; D018709:Statistics, Nonparametric; D015898:Tomography Scanners, X-Ray Computed; D014628:Vagotomy
keywords: Acute respiratory failure; CT scan; Diaphragm electrical activity; Mechanical ventilation; Neural control of breathing