Resolution of Lung Injury after a Single Event of Aspiration

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.

Acute lung injury induced by whole gastric fluid: hepatic acute phase response contributes to increase lung antiprotease protection

“…For each animal, four whole lobe longitudinal sections (5 μm) were obtained and stained with hematoxylin-eosin for analysis by light microscopy as in [ 5 ], following ATS recommendations [ 21 ].…”

“…These effects include severe derangement of the alveolar capillary barrier with extravasation of plasma constituents from the vascular to the alveolar spaces, polymorphonuclear neutrophil recruitment and expression of pro-inflammatory mediators. Recently, we contributed to the understanding of resolution of the initial ALI induced by whole gastric juice in a rat model [ 5 ], showing that resolution involves an organizing pneumonia with granuloma formation, that later resolves.…”

“…The aim of our work was to investigate whether and to what extent aspiration of gastric fluid induces a hepatic acute phase response in a rat model of orotracheal instillation of whole gastric fluid, and if so, to determine the effects of this response on lung antiprotease levels. This model has been well characterized by our group according to ATS recommendations [ 21 ], and meets all the requirements for a model of ALI with severe histological and physiological changes, which resolve leaving normal lung architecture [ 5 ].…”

Elastin degradation products in acute lung injury induced by gastric contents aspiration

“…Our group has addressed the study of the continuum of changes after a single event of bilateral aspiration of whole gastric contents and has shown that a single orotracheal instillation of gastric fluid in the rat lung results in severe acute lung injury with several histological similarities to diffuse alveolar damage (DAD), that evolves to an organization process involving intraluminal plugs of myofibroblasts and collagen fibers, affecting small bronchioles, alveolar ducts and peribronchiolar alveolar spaces, associated with particle-containing foreign-body giant cells either isolated or forming granulomas that later resolves [18]. This sequence of events reflects important remodeling of lung extracellular matrix (ECM) involving deposition and degradation of its components.…”

“…In our model, a 15- to 20-fold increase in bronchoalveolar lavage fluid (BALF) total cell count was found in the first 24 h after a single instillation of gastric fluid, with polymorphonuclear (PMN) cell predominance [18], an important source of elastase and free radicals, with the potential of damaging lung elastic tissue [28]. In addition to the inflammatory reaction induced by aspiration, elastic tissue damage could be produced by the direct effect of gastric fluid or could be part of the changes that take place in the remodeling of lung ECM after aspiration.…”