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Background: Because pulmonary endogenous surfactant is altered during acute respiratory distress syndrome, surfactant replacement may improve clinical outcomes. However, trials of surfactant use have had mixed results. We designed this animal model of unilateral (right) lung injury to explore the effect of exogenous surfactant administered to the injured lung on inflammation in the injured and noninjured lung., Methods: Mice underwent hydrochloric acid instillation (1.5 mL/kg) into the right bronchus and prolonged (7 hours) mechanical ventilation (25 mL/kg). After 3 hours, mice were treated with 1 mL/kg exogenous surfactant (Curosurf®) (surf group) or sterile saline (NaCl 0.9%) (vehicle group) in the injured (right) lung or did not receive any treatment (hydrochloric acid, ventilator-induced lung injury). Gas exchange, lung compliance, and bronchoalveolar inflammation (cells, albumin, and cytokines) were evaluated. After a significant analysis of variance (ANOVA) test, Tukey post hoc test was used for statistical analysis., Results: At least 8 to 10 mice in each group were analyzed for each evaluated variable. Surfactant treatment significantly increased both the arterial oxygen tension to fraction of inspired oxygen ratio and respiratory system static compliance (P = 0.027 and P = 0.007, respectively, for surf group versus vehicle). Surfactant therapy increased indices of inflammation in the acid-injured lung compared with vehicle: inflammatory cells (685 [602-773] and 216 [125-305] × 1000/mL, respectively; P < 0.001) and albumin in bronchoalveolar lavage (BAL) (1442 ± 588 and 743 ± 647 μg/mL, respectively; P = 0.027). These differences were not found (P = 0.96 and P = 0.54) in the contralateral (uninjured) lung (inflammatory cells 131 [78-195] and 119 [87-149] × 1000/mL and albumin 135 ± 100 and 173 ± 115 μg/mL)., Conclusions: Exogenous surfactant administration to an acid-injured right lung improved gas exchange and whole respiratory system compliance. However, markers of inflammation increased in the right (injured) lung, although this result was not found in the left (uninjured) lung. These data suggest that the mechanism by which surfactant improves lung function may involve both uninjured and injured alveoli.

Background: Acid aspiration is a complication of general anesthesia. Most animal models developed to define its pathophysiology have focused on the acute (< or =24 h) phase of the injury. The authors describe a model of acid aspiration allowing the study of this type of lung injury over time., Methods: The authors instilled hydrochloric acid (0.1 m, 1.5 ml/kg) or normal saline in the right bronchus of mice. Lung injury was evaluated at 6 h, 12 h, 24 h, and 2 weeks by assessing arterial blood gases, respiratory system compliance, lung wet weight normalized by body weight, lung myeloperoxidase activity, and histology. Twelve hours and 2 weeks after injury, a computed tomography scan was obtained., Results: In the hydrochloric acid group, arterial oxygen tension decreased (P < 0.05) at 12 and 24 h, whereas it recovered at 2 weeks; respiratory system compliance was lower both at 24 h and 2 weeks (P < 0.05). Lung weight increased at 12 and 24 h (P < 0.05). Myeloperoxidase activity peaked between 6 and 12 h. Computed tomography at 12 h showed that almost 30% of the injured lung was abnormally aerated. Although reduced, the abnormalities were still present at 2 weeks as confirmed by a fibrotic scar well evident at histologic examination., Conclusion: The authors characterized a murine model of regional acid aspiration allowing long-term survival. Despite a partial recovery, at 2 weeks the injury persisted, with evidence of fibrosis and lung compliance reduction. This long-term, low-mortality model seems suitable for assessment of the effects of different therapies on lung injury and repair.