In:
Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 103, No. 3 ( 2005-09-01), p. 556-566
Abstract:
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 & lt; 0.05) and consequently also in diminished neutrophil recruitment (36% fewer neutrophils; P & lt; 0.01). Treatment with pyrrolidine dithiocarbamate was highly effective in decreasing neutrophil recruitment (66%; P & lt; 0.01) and vascular permeability (80%; P & lt; 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.
Type of Medium:
Online Resource
ISSN:
0003-3022
DOI:
10.1097/00000542-200509000-00019
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2005
detail.hit.zdb_id:
2016092-6
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