dc.contributor.author
Müller-Redetzky, Holger C
dc.contributor.author
Will, Daniel
dc.contributor.author
Hellwig, Katherina
dc.contributor.author
Kummer, Wolfgang
dc.contributor.author
Tschernig, Thomas
dc.contributor.author
Pfeil, Uwe
dc.contributor.author
Paddenberg, Renate
dc.contributor.author
Menger, Michael D.
dc.contributor.author
Kershaw, Olivia
dc.contributor.author
Gruber, Achim Dieter
dc.contributor.author
Weissmann, Norbert
dc.contributor.author
Hippenstiel, Stefan
dc.contributor.author
Suttorp, Norbert
dc.contributor.author
Witzenrath, Martin
dc.date.accessioned
2018-06-08T02:53:19Z
dc.date.available
2015-06-11T08:51:02.883Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/14078
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-18275
dc.description.abstract
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.
en
dc.rights.uri
http://creativecommons.org/licenses/by/2.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::630 Landwirtschaft
dc.title
Mechanical ventilation drives pneumococcal pneumonia into lung injury and
sepsis in mice
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Critical Care. - 18 (2014), 2, Artikel Nr. R73
dc.identifier.sepid
39578
dc.title.subtitle
protection by adrenomedullin
dcterms.bibliographicCitation.doi
10.1186/cc13830
dcterms.bibliographicCitation.url
http://dx.doi.org/10.1186/cc13830
refubium.affiliation
Veterinärmedizin
de
refubium.affiliation.other
Institut für Tierpathologie
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refubium.mycore.fudocsId
FUDOCS_document_000000022593
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000005030
dcterms.accessRights.openaire
open access
dcterms.isPartOf.issn
1364-8535