N-acetylcysteine attenuates lung injury in a rodent model of fracture.
BACKGROUND
Neutrophil-mediated lung injury is a cause of significant morbidity and mortality in patients with multiple injuries. We have shown previously that fracture hematoma can activate neutrophils and is thus a putative mediator of the systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF) in those patients with severe skeletal trauma. Our aim was to establish a rodent model of fracture which caused lung injury and subsequently to administer a drug following fracture to attenuate the lung injury. The drug we chose was N-acetylcysteine, a potent antioxidant.


METHODS
Adult Sprague-Dawley rats were assigned to 4 groups: (1) general anesthetic only, (2) general anesthetic with bilateral femur fractures and nailing, (3) general anesthetic and N-acetylcysteine, (4) general anesthetic with bilateral femur fractures and nailing and N-acetylcysteine after the injury (n = 6 in each group). The dose of N-acetylcysteine was 0.5 mg/kg which was given intraperitoneally after injury to the treated groups. The rats were killed 24 hours after injury and some parameters of lung injury were evaluated--i.e., bronchoalveolar lavage (BAL), lung tissue myeloperoxidase levels (MPO) and wet/dry ratios of lung tissue. The results were analyzed, using one-way analysis of variance.


RESULTS
Bilateral femur fracture produced a significant lung injury, measured by increases in MPO (25-43 microg/g tissue) and BAL protein (460-605 microg/mL). This effect was attenuated by treatment with N-acetylcysteine (MPO 43-9 microg/mL, BAL protein 605-198 microg/mL).


CONCLUSIONS
N-acetyl cysteine, if given after skeletal trauma, is of potential therapeutic benefit, in preventing SIRS, ARDS and MOF.
Timlin
Marcus
M
Department of Orthopaedics, RCSI Education & Research Centre, Beaumont Hospital, Dublin 9, Ireland. marcustimlin@eircom.ne
Condron
Claire
C
Toomey
Deirdre
D
Power
Colm
C
Thornes
Brian
B
Kearns
Stephen
S
Street
John
J
Murray
Paraic
P
Bouchier-Hayes
David
D
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000150:complications* / Q000378:metabolism / Q000601:surgery; D005594:Fracture Fixation, Intramedullary / Q000009:adverse effects*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008297:Male; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*
D016166:Free Radical Scavengers; D009195:Peroxidase; D000111:Acetylcysteine