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Nebulized Hypertonic Saline Attenuates Acute Lung Injury Following Trauma and Hemorrhagic Shock via Inhibition of Matrix metalloproteinase-13

Nebulized Hypertonic Saline Attenuates Acute Lung Injury Following Trauma and Hemorrhagic Shock via Inhibition of Matrix metalloproteinase-13

Max Wohlauer, Ernest E Moore, Christopher C Silliman, Miguel Fragoso, Fabia Gamboni, Jeffrey Harr, Frank Accurso, Frank Wright, James Haenel, David Fullerton, Anirban Banerjee

Crit Care Med. 2012 Sep;40(9):2647-53.

PMID: 22732292

Abstract:

Objective:
We hypothesized that aerosolized inhaled hypertonic saline given at the onset of resuscitation will decrease acute lung injury following hemorrhagic shock, by inhibiting the release of epithelial derived proinflammatory mediators.
Design:
Animal study.
Setting:
Animal-care facility procedure room in a medical center.
Subjects:
Adult male Sprague-Dawley rats.
Interventions:
Rats underwent hemorrhagic shock followed by 2 hrs of resuscitation and 1 hr of observation. In the study group, nebulized hypertonic saline was delivered at the end of the shock period and after 1 hr and 2 hrs of resuscitation.
Measurements and main results:
Shock provoked acute lung injury, which was attenuated with inhaled hypertonic saline (1.56 ± 0.2 mg protein/mL vs. 0.95 ± 0.3 mg protein/mL bronchoalveolar lavage fluid, shock vs. shock + hypertonic saline, p < .01). Nebulized hypertonic saline reduced inflammation (cytokine-induced neutrophil chemoattractant-1 accumulation in bronchoalveolar lavage fluid 5999 ± 1267 pg/mL vs. 3342 ± 859 pg/mL, shock vs. shock + hypertonic saline, p = .006). Additionally, nebulized hypertonic saline inhibited matrix -metalloproteinase-13 accumulation in the bronchoalveolar lavage fluid (1513 ± 337 pg/mL bronchoalveolar lavage fluid vs. 230 ± 19 pg/mL, shock vs. shock + hypertonic saline, p = .009) and pretreatment with a matrix metalloproteinase-13 inhibitor was sufficient to attenuate postshock acute lung injury (1.42 ± 0.09 mg/mL vs. 0.77 ± 0.23 mg/mL bronchoalveolar lavage protein, shock vs. shock + matrix metalloproteinase-13 inhibitor CL-82198, p = .002).
Conclusion:
Inhaled hypertonic saline attenuates postshock acute lung injury by exerting an anti-inflammatory effect on the pulmonary epithelium, suggesting a new clinical strategy to treat acute lung injury/acute respiratory distress syndrome.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP307002717	CL-82198		307002-71-7	Price

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