Conflicting physiological and genomic cardiopulmonary effects of recruitment maneuvers in murine acute lung injury

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

Research output: Contribution to journalArticle

20 Scopus citations

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; μml/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.

Original languageEnglish (US)
Pages (from-to)541-550
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume46
Issue number4
DOIs
StatePublished - Apr 1 2012

Keywords

  • Acute lung injury
  • Mechanical ventilation
  • Microarray
  • Pulmonary hypertension
  • Right ventricle

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Dessap, A. M., Voiriot, G., Zhou, T., Marcos, E., Dudek, S. M., Jacobson, J. R., Machado, R., Adnot, S., Brochard, L., Maitre, B., & Garcia, J. G. N. (2012). Conflicting physiological and genomic cardiopulmonary effects of recruitment maneuvers in murine acute lung injury. American journal of respiratory cell and molecular biology, 46(4), 541-550. https://doi.org/10.1165/rcmb.2011-0306OC