N-acetylcysteine attenuates lung ischemia-reperfusion injury after lung transplantation.
BACKGROUND
Early acute graft dysfunction continues to be a problem after lung transplantation and results in significant postoperative morbidity and mortality. This study assessed the protective effect of N-acetylcysteine (NAC) on posttransplant lung ischemia-reperfusion injury.


METHODS
Rat single-lung transplantation was performed in two experimental groups (n = 5) after 18 hours of cold (4 degrees C) ischemia. Group I was the ischemic control (IC) group. In group II (NAC), donor and recipient animals were treated with an intraperitoneal injection of 150 mg/kg NAC 15 minutes before harvest, and recipient animals were treated again before reperfusion. After 2 hours of reperfusion, oxygenation was measured. Lung tissue was assessed for lipid peroxidation, neutrophil infiltration, and reduced glutathione level. Peak airway pressure was recorded throughout the reperfusion period.


RESULTS
Rats treated with NAC showed significantly better oxygenation (184.5 +/- 83.3 mm Hg versus 67.3 +/- 16.4 mm Hg, p = 0.016) and reduced lipid peroxidation (7.34 +/- 1.9 micromol/g versus 17.46 +/- 10.6 micromol/g, p = 0.016). Lung tissue reduced glutathione levels were 6.8 +/- 0.9 microM in the IC group and 20.6 +/- 2.4 microM in the NAC group (p = 0.004). Peak airway pressure at the end of the reperfusion period was 14.4 +/- 1.6 cm H2O in the NAC group, and 19.2 +/- 2.2 cm H2O in the IC group (p = 0.008). Myeloperoxidase activity and the ratio of wet-to-dry weight did not differ between the groups.


CONCLUSIONS
In this model, exogenously administered NAC effectively protected the lungs from reperfusion injury after prolonged ischemia.
Inci
Ilhan
I
Division of Thoracic Surgery, University of Zurich, Zurich, Switzerland.
Zhai
Wei
W
Arni
Stephan
S
Hillinger
Sven
S
Vogt
Peter
P
Weder
Walter
W
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D005978:Glutathione / Q000032:analysis; D015227:Lipid Peroxidation; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000517:prevention & control*; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D009195:Peroxidase; D005978:Glutathione; D000111:Acetylcysteine