Substance P and neutral endopeptidase in development of acute respiratory distress syndrome following fire smoke inhalation

2004 ◽  
Vol 287 (4) ◽  
pp. L859-L866 ◽  
Author(s):  
Simon S. Wong ◽  
Nina N. Sun ◽  
R. Clark Lantz ◽  
Mark L. Witten

To characterize the tachykininergic effects in fire smoke (FS)-induced acute respiratory distress syndrome (ARDS), we designed a series of studies in rats. Initially, 20 min of FS inhalation induced a significant increase of substance P (SP) in bronchoalveolar lavage fluid (BALF) at 1 h and persisted for 24 h after insult. Conversely, FS disrupted 51.4, 55.6, 46.3, and 43.0% enzymatic activity of neutral endopeptidase (NEP, a primary hydrolyzing enzyme for SP) 1, 6, 12, and 24 h after insult, respectively. Immunolabeling density of NEP in the airway epithelium largely disappeared 1 h after insult due to acute cell damage and shedding. These changes were also accompanied by extensive influx of albumin and granulocytes/lymphocytes in BALF. Furthermore, levels of BALF SP and tissue NEP activity dose dependently increased and decreased, respectively, following 0, low (10 min), and high (20 min) levels of FS inhalation. However, neither the time-course nor the dose-response study observed a significant change in the highest affinity neurokinin-1 receptor (NK-1R) for SP. Finally, treatment (10 mg/kg im) with SR-140333B, an NK-1R antagonist, significantly prevented 20-min FS-induced hypoxemia and pulmonary edema 24 h after insult. Further examination indicated that SR-140333B (1.0 or 10.0 mg/kg im) fully abolished early (1 h) plasma extravasation following FS. Collectively, these findings suggest that a combination of sustained SP and NEP inactivity induces an exaggerated neurogenic inflammation mediated by NK-1R, which may lead to an uncontrolled influx of protein-rich edema fluid and cells into the alveoli as a consequence of increased vascular permeability.

Shock ◽  
2020 ◽  
Vol 53 (3) ◽  
pp. 317-326 ◽  
Author(s):  
Ernesto Lopez ◽  
Osamu Fujiwara ◽  
Christina Nelson ◽  
Melissa E. Winn ◽  
Richard S. Clayton ◽  
...  

2019 ◽  
Vol 87 ◽  
pp. S91-S100 ◽  
Author(s):  
Andriy I. Batchinsky ◽  
Ruth Wyckoff ◽  
Jae-Hyek Choi ◽  
David Burmeister ◽  
Bryan S. Jordan ◽  
...  

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Alexandre Gaudet ◽  
Erika Parmentier ◽  
Sylvain Dubucquoi ◽  
Julien Poissy ◽  
Thibault Duburcq ◽  
...  

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Katherine Marie Ivey ◽  
Andriy Batchinsky ◽  
Thomas Langer ◽  
Slava Belenkiy ◽  
Corina Necsiou ◽  
...  

2016 ◽  
Vol 30 (6) ◽  
pp. 663-667 ◽  
Author(s):  
Kevin M. Dube ◽  
Kristen L. Ditch ◽  
Luanne Hills

Smoke inhalation injury (SIJ) is associated with an increase in morbidity and mortality in patients with burns. SIJ causes airway damage, inflammation, and bronchial obstruction, resulting in decreased oxygenation and perfusion status in these patients. Retrospective studies have compared the use of nebulized heparin (NH) plus nebulized N-acetylcysteine (NAC) and albuterol in patients with SIJ to those who received standard ventilator support with bronchodilator therapy. These studies are associated with a decrease in mortality when NH and nebulized NAC are administered to patients with SIJ. Approximately 20% of patients who develop SIJ will also develop acute respiratory distress syndrome (ARDS). Epoprostenol, a selective pulmonary vasodilator, has been utilized in the treatment of ARDS with mixed results for improving gas exchange. To our knowledge, this is the first case report of the concomitant administration of NH, nebulized NAC, and nebulized epoprostenol following SIJ in a burn patient with ARDS.


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