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Characterization of a double-hit murine model of Acute Respiratory Distress Syndrome.
MedLine Citation:
PMID:  25115497     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
RATIONALE: The definition of acute respiratory distress syndrome (ARDS) has changed during the last years and with it the requirements for animal models that try to reproduce all defining criteria of human ARDS.
OBJECTIVE: The aim of this study was to characterize a murine model of ARDS abiding by the new Berlin Definition of human ARDS and guidelines for animal models of ARDS.
METHODS: C57BL/6NCrl mice were challenged with an intraperitoneal injection of lipopolysaccharide (LPS; 15mg/kgBW) followed by intravenous oleic acid (OA; 0.12ml/kgBW) 18 hours later. Controls received saline respectively. Hemodynamics were monitored continuously. Arterial blood gas analyses were made every 30 minutes. After 90 minutes, micro-computed tomography scanning of the chest was performed. Cytokine concentrations were measured in plasma samples. Lungs were harvested for histology, immuno-histochemistry, lung weight measurements, and tissue cytokine detection. A histologic lung injury score was determined.
RESULTS: 18 hours after LPS challenge mice expressed a severe systemic inflammatory response syndrome. Oxygenation declined significantly after OA application (PaO2 /FiO2 60min: 283±73mmHg, 90min: 256±71mmHg; p<0.001). Bilateral patchy infiltrates were present upon CT scans. Histology revealed parenchymal damage with an accumulation of polymorphonuclear neutrophils, intraalveolar proteinacous debris and few hyaline membranes. Lung wet-dry-ratio displayed damage to the alveolar capillary membrane. Cytokine patterns proofed a severe local and systemic inflammatory state in plasma and lung tissue.
CONCLUSION: This two-hit model of ARDS shows a complex pathological picture of ARDS closely mimicking a human ARDS as described by the Berlin Definition and therefore might facilitate interpretation of prospective experimental results. This article is protected by copyright. All rights reserved.
Authors:
Mt Voelker; F Fichtner; M Kasper; M Kamprad; U Sack; Ux Kaisers; S Laudi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-12
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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