title: Resolution of lung injury after a single event of aspiration: a model of bilateral instillation of whole gastric fluid.
abstract: Gastric aspiration is a high-risk condition for lung injury. Consequences range from subclinical pneumonitis to respiratory failure, with fibrosis development in some patients. Little is known about how the lung repairs aspiration-induced injury. By using a rat model of single orotracheal instillation of whole gastric contents, we studied the time course of morphological and biochemical changes during injury and resolution, and evaluated whether repair involved long-term fibrosis. Anesthetized rats received one gastric fluid instillation. At 4, 12, and 24 hours and 4 and 7 days, we performed lung histological studies and biochemical measurements in bronchoalveolar lavage fluid and lung tissue. Physiological measurements were performed at 12 to 24 hours. Long-term outcome was studied histologically at day 60. During the first 24 hours, severe peribronchiolar injury involving edema, intra-alveolar proteinaceous debris, hemorrhage, increased neutrophils and cytokines, and physiological dysfunction were observed. At days 4 and 7, an organizing pneumonia (OP) pattern developed, with foreign-body giant cells and granulomas. Lung matrix metalloproteinase 9 and 2 activities increased, with metalloproteinase-9 linked to early inflammation and metalloproteinase-2 to OP. At day 60, lung architecture was normal. In conclusion, a continuum of alterations starting with severe injury, evolving toward OP and later resolving, characterizes the rat single aspiration event. In addition to identifying markers of staging and severity, this model reveals that OP participates in the repair of aspiration-induced injury.
authors: Department of Respiratory Diseases and Medical Research Center, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Joaquín D
authors: JD
authors: Araos
authors: Department of Respiratory Diseases and Medical Research Center, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Pedro S
authors: PS
authors: Ayala
authors: Department of Pathology, Instituto Nacional del Tórax, Santiago, Chile.
authors: Manuel
authors: M
authors: Meneses
authors: Department of Respiratory Diseases and Medical Research Center, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Rafael
authors: R
authors: Contreras
authors: Department of Respiratory Diseases and Medical Research Center, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Andrea
authors: A
authors: Cutiño
authors: Department of Respiratory Diseases and Medical Research Center, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Rebeca M
authors: RM
authors: Montalva
authors: Department of Pathology, Mayo Clinic, Scottsdale, Arizona.
authors: Henry D
authors: HD
authors: Tazelaar
authors: Department of Respiratory Diseases and Medical Research Center, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: gborzone@med.puc.cl.
authors: Gisella R
authors: GR
authors: Borzone
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005750:Gastric Juice / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000166:cytology; D011014:Pneumonia / Q000473:pathology; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines