Nebulized hypertonic saline attenuates acute lung injury following trauma and hemorrhagic shock via inhibition of matrix metalloproteinase-13
Max Wohlauer 1, Ernest E Moore, Christopher C Silliman, Miguel Fragoso, Fabia Gamboni, Jeffrey Harr, Frank Accurso, Frank Wright, James Haenel, David Fullerton, Anirban Banerjee

Objective: We hypothesized that aerosolized inhaled hypertonic saline given in the start of resuscitation will decrease acute lung injuries following hemorrhagic shock, by inhibiting the discharge of epithelial derived proinflammatory mediators.

Design: Animal study.

Setting: Animal-care facility procedure room inside a clinic.

Subjects: Adult male Sprague-Dawley rats.

Interventions: Rats went through hemorrhagic shock adopted by 2 hrs of resuscitation and 1 hr of observation. Within the study group, nebulized hypertonic saline was delivered in the finish from the shock period after 1 hr and a pair of hrs of resuscitation.

Measurements and primary results: Shock triggered acute lung injuries, that was attenuated with inhaled hypertonic saline (1.56 ?¨¤ .2 mg protein/mL versus. .95 ?¨¤ .3 mg protein/mL bronchoalveolar lavage fluid, shock versus. 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.