title: Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities.
abstract: It is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation.
  
  
  
  In a small animal model, synchrotron imaging was used to measure lung aeration and regional-specific ventilation (sV̇). Heterogeneity of ventilation was calculated as the coefficient of variation in sV̇ (CVsV̇ ). The coefficient of variation in lung densities (CVD ) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end-expiratory pressure (ZEEP) and FI O2 0.21; ZEEP and FI O2 1.0; PEEP 12 cmH2 O and FI O2 1.0 (Open Lung-PEEP = OLP).
  
  
  
  The mean tissue density at OLP was lower than ZEEP-1.0 and ZEEP-0.21. There were larger subregions with low sV̇ and poor aeration at ZEEP-0.21 than at OLP: 12.9 ± 9.0 vs. 0.6 ± 0.4% in the non-dependent level, and 17.5 ± 8.2 vs. 0.4 ± 0.1% in the dependent one (P = 0.041). The CVsV̇ of the total imaged lung at PEEP 12 cmH2 O was significantly lower than on ZEEP, regardless of FI O2 , indicating more heterogeneity of ventilation during ZEEP (0.23 ± 0.03 vs. 0.54 ± 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP.
  
  
  
  ZEEP together with low FI O2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions.
authors.affiliation: Hedenstierna Laboratory, Department of Surgical Sciences, Section of Anaesthesiology & Critical Care, Uppsala University, Uppsala, Sweden.|Pulmonary Divison, Heart Institute (Incor) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
authors.forename: J B
authors.initials: JB
authors.lastname: Borges
authors.affiliation: Department of Physics, University of Helsinki, Helsinki, Finland.|Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Porra
authors.affiliation: Department of Emergency and Organ Transplant, Bari University, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: Department of Emergency and Organ Transplant, Bari University, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tannoia
authors.affiliation: Department of Emergency and Organ Transplant, Bari University, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Derosa
authors.affiliation: Hedenstierna Laboratory, Department of Surgical Sciences, Section of Anaesthesiology & Critical Care, Uppsala University, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Inserm UMR1105 and Pediatric Lung Function Laboratory, CHU Amiens, Université de Picardie Jules Verne, Amiens, France.
authors.forename: S
authors.initials: S
authors.lastname: Bayat
authors.affiliation: Hedenstierna Laboratory, Department of Surgical Sciences, Section of Anaesthesiology & Critical Care, Uppsala University, Uppsala, Sweden.|Department of Emergency and Organ Transplant, Bari University, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Perchiazzi
authors.affiliation: Hedenstierna Laboratory, Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Hedenstierna
mesh_terms: D000818:Animals; D008168:Lung; D008170:Lung Compliance; D008171:Lung Diseases; D010100:Oxygen; D011175:Positive-Pressure Respiration
chemical_list: D010100:Oxygen