Lung injury and recovery in a murine model of unilateral acid aspiration: functional, biochemical, and morphologic characterization

Anesthesiology. 2008 Jun;108(6):1037-46. doi: 10.1097/ALN.0b013e318173f64f.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Gas Analysis
  • Disease Models, Animal*
  • Female
  • Fibrosis / chemically induced
  • Fibrosis / pathology
  • Hydrochloric Acid / administration & dosage
  • Hydrochloric Acid / toxicity*
  • Instillation, Drug
  • Lung / drug effects*
  • Lung / pathology
  • Lung / physiopathology
  • Lung Compliance / drug effects
  • Mice
  • Organ Size / drug effects
  • Peroxidase / drug effects
  • Pneumonia, Aspiration / chemically induced*
  • Pneumonia, Aspiration / pathology
  • Pneumonia, Aspiration / physiopathology
  • Random Allocation
  • Recovery of Function
  • Respiratory Aspiration* / pathology
  • Respiratory Aspiration* / physiopathology
  • Sodium Chloride / administration & dosage
  • Time Factors
  • Tomography, X-Ray Computed

Substances

  • Sodium Chloride
  • Peroxidase
  • Hydrochloric Acid