Acute lung injury secondary to hydrochloric acid instillation induces small airway hyperresponsiveness

Background: Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure characterized by altered lung mechanics and poor oxygenation. Bronchial hyperresponsiveness has been reported in ARDS survivors and animal models of acute lung injury. Whether this hyperreactivity occurs at the small airways or not is unknown. Objective: To determine ex-vivo small airway reactivity in a rat model of acute lung injury (ALI) by hydrochloric acid (HCl) instillation. Methods: Twelve anesthetized rats were connected to mechanical ventilation for 4-hour, and randomly allocated to either ALI group (HCl intratracheal instillation; n=6) or Sham (intratracheal instillation of 0.9% NaCl; n=6). Oxygenation was assessed by arterial blood gases. After euthanasia, tissue samples from the right lung were harvested for histologic analysis and wet-dry weight ratio assessment. Precision cut lung slice technique (100-200 pm diameter) was applied in the left lung to evaluate ex vivo small airway constriction in response to histamine and carbachol stimulation, using phase-contrast video microscopy. Results: Rats from the ALI group exhibited hypoxemia, worse histologic lung injury, and increased lung wet-dry weight ratio as compared with the sham group. The bronchoconstrictor responsiveness was significantly higher in the ALI group, both for carbachol (maximal contraction of 84.5 +/- 2.5% versus 61.4 +/- 4.2% in the Sham group, P<0.05), and for histamine (maximal contraction of 78.6 +/- 5.3% versus 49.6 +/- 5.3% in the Sham group, P<0.05). Conclusion: In an animal model of acute lung injury secondary to HCL instillation, small airway hyperresponsiveness to carbachol and histamine is present. These results may provide further insight into the pathophysiologi of ARDS.