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    Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice:
    protection by adrenomedullin (2014)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Müller-Redetzky, Holger C
    Will, Daniel
    Hellwig, Katharina
    Kummer, Wolfgang
    Tschernig, Thomas
    Pfeil, Uwe
    Paddenberg, Renate
    Menger, Michael D
    Kershaw, Olivia (WE 12)
    Gruber, Achim D (WE 12)
    Weissmann, Norbert
    Hippenstiel, Stefan
    Suttorp, Norbert
    Witzenrath, Martin
    Quelle
    Critical care (London, England); 18(2) — S. R73
    ISSN: 1466-609x
    Sprache
    Englisch
    Verweise
    URL (Volltext): http://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000022593
    DOI: 10.1186/cc13830
    Pubmed: 24731244
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    Institut für Tierpathologie

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    14163 Berlin
    +49 30 838 62450

    Abstract / Zusammenfassung

    Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia.

    We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation.

    In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p<0.01; prevention of pulmonary restriction) and against VILI-induced liver and gut injury in pneumonia (91% reduction of AST levels p<0.05, 96% reduction of alanine aminotransaminase (ALT) levels p<0.05, abrogation of histopathological changes and parenchymal apoptosis in liver and gut).

    MV paved the way for the progression of pneumonia towards ARDS and sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.