Nebulized hypertonic saline attenuates acute lung injury following trauma and hemorrhagic shock via inhibition of matrix metalloproteinase-13

• Published in: Critical care medicine Vol. 40; no. 9; p. 2647
• Main Authors: Wohlauer, Max, Moore, Ernest E, Silliman, Christopher C, Fragoso, Miguel, Gamboni, Fabia, Harr, Jeffrey, Accurso, Frank, Wright, Frank, Haenel, James, Fullerton, David, Banerjee, Anirban
• Format: Journal Article
• Language: English
• Published: United States 01.09.2012
• Subjects: Acute Lung Injury - drug therapy; Acute Lung Injury - etiology; Acute Lung Injury - pathology; Administration, Inhalation; Animals; Biopsy, Needle; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Immunohistochemistry; Male; Matrix Metalloproteinase 13 - drug effects; Matrix Metalloproteinase 13 - metabolism; Nebulizers and Vaporizers; Neutrophil Infiltration - physiology; Random Allocation; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome, Adult - drug therapy; Respiratory Distress Syndrome, Adult - etiology; Respiratory Distress Syndrome, Adult - pathology; Saline Solution, Hypertonic - pharmacology; Sensitivity and Specificity; Shock, Hemorrhagic - complications; Wounds and Injuries - complications
• ISSN: 1530-0293
• DOI: 10.1097/ccm.0b013e3182592006

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. Animal study. Animal-care facility procedure room in a medical center. Adult male Sprague-Dawley rats. 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. 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). 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.