Introduction and Objectives Aspiration pneumonitis is an important risk factor for acute lung injury/acute respiratory distress syndrome (ALI/ARDS).1 Animals models of ALI should ideally mimic the human situation, although to date none fully reflect the complex pathophysiology involved. Our objective was to develop, optimise and characterise a model of acid aspiration that would closely resemble clinical ALI/ARDS including both inflammatory and recovery phases. While longer-term animal models of acid aspiration have been utilised, their clinical applicability has been limited by high mortality or use of unilateral pulmonary instillation2.
Methods C57Bl6 mice were anaesthetized, orotracheally catheterised and instilled with 75 μl of 0.1 M hydrochloric acid. They were recovered with FiO2 of 0.4 for 6 h and then placed in room air. At pre-determined time points they underwent tracheostomy, low tidal volume ventilation (8 ml/kg), and arterial catheter placement. Respiratory system mechanics and arterial oxygenation were determined, and following termination, bronchoalveolar lavage (BAL) was sampled for neutrophil infiltration and total protein concentration.
Results Following acid aspiration mice showed significant weight loss, decreased PaO2:FiO2 ratios and increased respiratory system elastance compared to untreated controls. There was significant pulmonary endothelial/epithelial leak as measured by BAL protein concentration, as well as substantial neutrophil influx. Changes in all of these parameters were transient, peaking on days 1–3 and then resolving to near baseline by day 10 (Abstract P252 Table 1).
|Control||Day 1||Day 2||Day 3||Day 5||Day 10|
|Weight Loss (%) (N=5-11)||–||−7.0± 2.3||−13.3± 4.9||−13.3± 4.0||−7.3± 2.5||−2.9± 1.9|
|PaO2:FiO2 (N=3–5)||507± 37||162± 97***||310± 74*||158± 69**||359± 97||538± 11|
|Respiratory Elastance (cmH20/μl) (N=3–4)||0.028± 0.002||0.061± 0.018***||0.065± 0.008***||0.035± 0.003||0.032± 0.002||0.027± 0.001|
|BAL Protein Conc. (mg/ml) (N=3–6)||0.15± 0.02||4.86± 0.47***||3.36± 0.56***||1.72± 0.89**||0.73± 0.20||0.31± 0.09|
|BAL Neutrophil Count (×104/ml) (N=3–4)||0.002± 0.004||5.7± 3.8||28.4± 5.1***||6.60± 0.63||0.47± 0.19||0.003± 0.001|
All timepoints compared with One-Way Analysis of Variance with Bonferroni test.
*** p<0.001, **p<0.01, *p<0.05 vs control.
Conclusion In this study, we describe a translational model of acid-induced lung injury that shows significant injury and inflammation resolving over a 10-day period. It shows many characteristics of clinical ALI/ARDS including severe hypoxaemia, worsening respiratory mechanics, alveolar-capillary barrier permeability, and neutrophilic infiltration within the alveolar space. This resolving model of aspiration pneumonitis may allow further elucidation of the pathophysiological mechanisms of ALI/ARDS and its resolution, in particular oedema formation and inflammatory cell recruitment.
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Funding This work was supported by the Wellcome Trust and National Institute of Academic Anaesthesia.
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