A novel rabbit model of severe ARDS: Synergistic effects of acid aspiration and harmful mechanical ventilation

Background

Acute respiratory distress syndrome (ARDS) is characterised by severe inflammation and pulmonary edema, often leading to respiratory failure. This study aims to develop a stable and relevant rabbit model of severe ARDS using hydrochloric acid (HCl) aspiration and ventilator-induced lung injury (VILI).

Methods

Adult New Zealand rabbits were divided into four groups: Saline (n = 9), 1-hit 3.0 (HCl 3 ml/kg, n = 7), 1-hit 6.0 (HCl 6 ml/kg, n = 7), and 2-hit (HCl 3 ml/kg and ventilation with V_T 20 ml/kg, zero PEEP, RR 20-30 bpm, and FiO₂ 1.0 to mimic VILI, n = 14). PaO₂/FiO₂ ratio, oxygenation index, oxygen saturation, PaCO₂, ventilation efficiency index and alveolar-arterial gradient were evaluated every hour for 4 h after induction of lung injury. The post-mortem analysis included total and differential cell counts in bronchoalveolar lavage fluid (BALF), evaluation of lung edema formation, biochemical and histological examination of lung tissue.

Results

In the 2-hit group, we observed a significant deterioration of all lung function parameters (P/F ratio, oxygenation index, ventilation efficiency index, and alveolar-arterial gradient) compared to the saline group. Similarly, a deterioration was observed in the 1-hit 6.0 group. When analysing the inflammatory profile, we observed significantly increased levels of chemokines and cytokines (TNFα, IL-1β, IL-6, IL-8, ET-1, MCP, H1F, MIP) and oxidative stress parameters (3NT, MDA, AOPP, catalase and GSH/GSSG) in BALF in the 2-hit group compared to the saline group. Intratracheal administration of HCl alone did not have a significant impact on inflammation as the combination of two insults. An increased wet-to-dry lung weight ratio (W/D), indicative of pulmonary edema, was observed in both the 2-hit and 1-hit 6.0 groups compared to the saline group. An increased level of protein content in BALF and total lung injury score were observed in the 2-hit group compared to the saline group, 1-hit 3.0 and 1-hit 6.0.

Conclusion

The combination of hydrochloric acid aspiration and ventilator-induced lung injury reliably reproduces key features of severe ARDS, offering a robust and clinically relevant model for investigating its complex pathophysiology and evaluating novel therapeutic interventions.