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Pulmonary aspiration: new therapeutic approaches in the experimental model
Beatrice Beck-Schimmer1, Dorothea S Rosenberger, Simona B Neff
1Institutes of Anesthesiology and Physiology, University of Zurich, Switzerland. beatrice_beck.schimmer@access.unizh.ch
Background:
Acute lung injury caused by gastric aspiration is a frequent occurrence in unconscious patients. Acute respiratory distress syndrome in association with gastric aspiration carries a mortality of up to 30% and accounts for up to 20% of deaths associated with anesthesia. Although the clinical condition is well known, knowledge about the exact inflammatory mechanisms is still incomplete. This study was performed to define the role of alveolar macrophages in this inflammatory response. In addition, potentially modifying effects of intratracheally applied nuclear factor kappaB inhibitor pyrrolidine dithiocarbamate were investigated.
Methods:
Rat alveolar macrophages were depleted by intratracheal administration of clodronate liposomes, and lung injury was evaluated 6 h after instillation of 0.1N hydrochloric acid. In a second set of experiments, pyrrolidine dithiocarbamate was intratracheally instilled 3 h after hydrochloric acid application, and injury parameters were determined.
Results:
Depletion of alveolar macrophages resulted in decreased production of inflammatory mediators in acid aspiration (23-80% reduction of messenger RNA or protein of inflammatory mediators; P < 0.05) and consequently also in diminished neutrophil recruitment (36% fewer neutrophils; P < 0.01). Treatment with pyrrolidine dithiocarbamate was highly effective in decreasing neutrophil recruitment (66%; P < 0.01) and vascular permeability (80%; P < 0.001).
Conclusions:
These data suggest that alveolar macrophages play an essential role in the inflammatory response of acid-induced lung injury. For the first time, attenuation of acid-induced lung injury with an inhibitor, applied after the onset of injury, is shown.
Insights
Alveolar macrophages are key drivers of lung injury from gastric aspiration. Inhibiting nuclear factor kappaB after injury significantly reduces inflammation and neutrophil infiltration, offering a potential therapeutic strategy.
Area of Science:
- Pulmonary Medicine
- Inflammation Research
- Critical Care
Background:
- Gastric aspiration causes acute lung injury and acute respiratory distress syndrome, with high mortality.
- Mechanisms of inflammatory response in acid-induced lung injury are not fully understood.
- Alveolar macrophages' role in this response requires further definition.
Purpose of the Study:
- To elucidate the role of alveolar macrophages in acid-induced lung injury.
- To investigate the therapeutic potential of nuclear factor kappaB inhibition.
Main Methods:
- Rat alveolar macrophages were depleted using clodronate liposomes.
- Lung injury was induced by intratracheal hydrochloric acid instillation.
- Nuclear factor kappaB inhibitor pyrrolidine dithiocarbamate was administered post-injury.
Main Results:
- Alveolar macrophage depletion reduced inflammatory mediators and neutrophil recruitment.
- Pyrrolidine dithiocarbamate significantly decreased neutrophil recruitment and vascular permeability.
- These findings highlight macrophages' critical role in acid aspiration injury.
Conclusions:
- Alveolar macrophages are essential in the inflammatory cascade of acid-induced lung injury.
- Post-injury application of a nuclear factor kappaB inhibitor effectively attenuates lung injury.
- This study demonstrates a novel therapeutic approach for acid aspiration lung injury.
