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

Abstract

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 V20 ml/kg, zero PEEP, RR 20-30 bpm, and FiO1.0 to mimic VILI, n = 14). PaO/FiOratio, oxygenation index, oxygen saturation, PaCO, 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.