title: Resolution of acute lung injury and inflammation: a translational mouse model.
abstract: Previous animal models of acute lung injury (ALI) are limited as they only reproduce part of the complex pathobiology of clinical ALI. Here we develop a translational mouse model of ALI, which not only reflects the major clinical and pathological features but also enables investigation into ALI resolution. Anaesthetised mice underwent orotracheal instillation of hydrochloric acid. During the immediate period after instillation, mice were carefully maintained with supplemental oxygen to avoid mortality. At specified time-points, lung injury was assessed by analysis of blood gases, respiratory mechanics, bronchoalveolar lavage fluid, alveolar fluid clearance and lung histology. Animals exhibited significant weight loss, decreased oxygenation, increased respiratory elastance and pulmonary inflammation (intra-alveolar leukocyte influx/cytokine levels and histological injury scores). Moreover, mice displayed alveolar-capillary barrier dysfunction/epithelial injury as reflected by increased alveolar protein, lung wet/dry weight ratio and soluble receptor for advanced glycation end-products, as well as reduced alveolar fluid clearance. These injury parameters peaked between days 1 and 3, followed by almost complete recovery over days 5-10. Histology showed evidence of fibrosis on day 10. The results indicate that this resolving model of acid aspiration represents a powerful experimental tool to investigate the injurious, inflammatory, fibrotic, and resolving and reparative processes of ALI.
authors: Section of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
authors: Brijesh V
authors: BV
authors: Patel
authors: Michael R
authors: MR
authors: Wilson
authors: Masao
authors: M
authors: Takata
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000628:therapy; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D006851:Hydrochloric Acid / Q000633:toxicity*; D008168:Lung / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils; D010100:Oxygen / Q000097:blood; D010102:Oxygen Inhalation Therapy; D011014:Pneumonia / Q000139:chemically induced* / Q000628:therapy; D011658:Pulmonary Fibrosis / Q000139:chemically induced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis; D020127:Recovery of Function; D012129:Respiratory Function Tests; D057170:Translational Research, Biomedical
chemical_list: D016207:Cytokines; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D006851:Hydrochloric Acid; D010100:Oxygen