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


METHODS
Animal study.


METHODS
Animal-care facility procedure room in a medical center.


METHODS
Adult male Sprague-Dawley rats.


METHODS
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.


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).


CONCLUSIONS
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.
Department of Surgery, University of Colorado Denver, CO, USA.
Max
M
Wohlauer
Ernest E
EE
Moore
Christopher C
CC
Silliman
Miguel
M
Fragoso
Fabia
F
Gamboni
Jeffrey
J
Harr
Frank
F
Accurso
Frank
F
Wright
James
J
Haenel
David
D
Fullerton
Anirban
A
Banerjee
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D000280:Administration, Inhalation; D000818:Animals; D001707:Biopsy, Needle; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000187:drug effects* / Q000378:metabolism*; D009330:Nebulizers and Vaporizers; D020556:Neutrophil Infiltration / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D012771:Shock, Hemorrhagic / Q000150:complications; D014947:Wounds and Injuries / Q000150:complications
D012462:Saline Solution, Hypertonic; D053509:Matrix Metalloproteinase 13