Document Detail


Conflicting physiological and genomic cardiopulmonary effects of recruitment maneuvers in murine acute lung injury.
MedLine Citation:
PMID:  22135358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Armand Mekontso Dessap; Guillaume Voiriot; Tong Zhou; Elisabeth Marcos; Steven M Dudek; Jeff R Jacobson; Roberto Machado; Serge Adnot; Laurent Brochard; Bernard Maitre; Joe G N Garcia
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-01
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  46     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-04     Completed Date:  2012-06-11     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  541-50     Citation Subset:  IM    
Affiliation:
INSERM, Unité U, Créteil, France.
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MeSH Terms
Descriptor/Qualifier:
Acute Lung Injury / blood,  genetics*,  physiopathology*
Animals
Bronchoalveolar Lavage Fluid
Chemokines / genetics
Cytokines / genetics
Disease Models, Animal
Gene Expression Regulation
Heart Ventricles / physiopathology
Lipopolysaccharides / toxicity
Lung / physiology
Mice
Mice, Inbred C57BL
Respiration, Artificial / methods
Tidal Volume
Transcriptome
Ventilator-Induced Lung Injury / physiopathology
Grant Support
ID/Acronym/Agency:
HL58094/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Chemokines; 0/Cytokines; 0/Lipopolysaccharides
Comments/Corrections

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