title: Conflicting physiological and genomic cardiopulmonary effects of recruitment maneuvers in murine acute lung injury.
abstract: Low tidal volume ventilation, although promoting atelectasis, is a protective strategy against ventilator-induced lung injury. Deep inflation (DI) recruitment maneuvers restore lung volumes, but potentially compromise lung parenchymal and vascular function via repetitive overdistention. Our objective was to examine cardiopulmonary physiological and transcriptional consequences of recruitment maneuvers. C57/BL6 mice challenged with either PBS or LPS via aspiration were placed on mechanical ventilation (5 h) using low tidal volume inflation (TI; 8 μl/g) alone or in combination with intermittent DIs (0.75 ml twice/min). Lung mechanics during TI ventilation significantly deteriorated, as assessed by forced oscillation technique and pressure-volume curves. DI mitigated the TI-induced alterations in lung mechanics, but induced a significant rise in right ventricle systolic pressures and pulmonary vascular resistances, especially in LPS-challenged animals. In addition, DI exacerbated the LPS-induced genome-wide lung inflammatory transcriptome, with prominent dysregulation of a gene cluster involving vascular processes, as well as increases in cytokine concentrations in bronchoalveolar lavage fluid and plasma. Gene ontology analyses of right ventricular tissue expression profiles also identified inflammatory signatures, as well as apoptosis and membrane organization ontologies, as potential elements in the response to acute pressure overload. Our results, although confirming the improvement in lung mechanics offered by DI, highlight a detrimental impact in sustaining inflammatory response and exacerbating lung vascular dysfunction, events contributing to increases in right ventricle afterload. These novel insights should be integrated into the clinical assessment of the risk/benefit of recruitment maneuver strategies.
authors.affiliation: INSERM, Unité U, Créteil, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Mekontso Dessap
authors.forename: Guillaume
authors.initials: G
authors.lastname: Voiriot
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Marcos
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dudek
authors.forename: Jeff R
authors.initials: JR
authors.lastname: Jacobson
authors.forename: Roberto
authors.initials: R
authors.lastname: Machado
authors.forename: Serge
authors.initials: S
authors.lastname: Adnot
authors.forename: Laurent
authors.initials: L
authors.lastname: Brochard
authors.forename: Bernard
authors.initials: B
authors.lastname: Maitre
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D012121:Respiration, Artificial / Q000379:methods; D013990:Tidal Volume; D059467:Transcriptome; D055397:Ventilator-Induced Lung Injury / Q000503:physiopathology
chemical_list: D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides