Characterization of a double‐hit murine model of acute respiratory distress syndrome

Abstract

The aim of the present study was to characterize a murine model of acute respiratory distress syndrome (ARDS) abiding by the Berlin definition of human ARDS and guidelines for animal models of ARDS. To this end, C57BL/6NCrl mice were challenged with lipopolysaccharide (LPS; 15 mg/kg, i.p.) followed 18 h later by injection of oleic acid (OA; 0.12 mL/kg, i.v.). Controls received saline injection at both time points. Haemodynamics were monitored continuously. Arterial blood gas analyses were performed just before and every 30 min after OA challenge. Ninety minutes after OA challenge, the chest of mice was scanned using micro-computed tomography (CT). Cytokine concentrations were measured in plasma samples. Lungs were harvested 90 min after OA challenge for histology, immunohistochemistry, lung weight measurements and tissue cytokine detection. A histological lung injury score was determined. Eighteen hours after LPS challenge, mice exhibited a severe systemic inflammatory response syndrome. Oxygenation declined significantly after OA injections (Pa o2 /Fi o2 283 ± 73 and 256 ± 71 mmHg at 60 and 90 min, respectively; P < 0.001). Bilateral patchy infiltrates were present on the micro-CT scans. Histology revealed parenchymal damage with accumulation of polymorphonuclear neutrophils, intra-alveolar proteinacous debris and few hyaline membranes. The lung wet : dry ratio indicated damage to the alveolar capillary membrane. Cytokine patterns evidenced a severe local and systemic inflammatory state in plasma and lung tissue. In conclusion, the described two-hit model of ARDS shows a pathological picture of ARDS closely mimicking human ARDS according to the Berlin definition and may facilitate interpretation of prospective experimental results.

Soluble Receptor for Advanced Glycation End-Products Predicts Impaired Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome

“…This novel finding could suggest an under investigated role for the IL-17-T helper 17 cell pathway during ARDS resolution and stimulate further research (29,30). The report of sRAGE plasma levels in lung injured mice is rather novel (31) and further supports the value of sRAGE as a surrogate marker of lung injury severity in general (10)(11)(12), and of AFC in particular, in both the experimental and clinical settings of ARDS. Because of the evidence that alveolar epithelial type I cells transport sodium and contribute to AFC(32, 33), a marker of AT I cell injury could reflect intact AFC.…”

Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

“…Also, the overall amount of TNF-α in the lungs was lower than in other experimental settings that applied much more potent triggers of inflammation, such as lipopolysaccharides (LPS). 36 …”

Novel swine model of ricin-induced acute respiratory distress syndrome

“…Research aimed to evaluate new therapeutic options judiciously tailored for effective treatment of ricin-induced pulmonary intoxication, requires the availability of an animal model that lends itself to continuous monitoring of respiratory and hemodynamic parameters. Although recent reports have shown that a mouse model can be utilized for assessment of pulmonary gas exchange and respiratory mechanics following controlled induction of acute respiratory distress syndrome (ARDS; Patel et al, 2012 , Voelker et al, 2014 ), mechanical ventilation and repeated blood sampling could be carried out in mice for only a very short time. These mice model systems are therefore not amenable with the surveillance of progression of ricin pathology where clinical symptoms can be discerned only many hours after exposure to the toxin and death occurs only within several days.…”