N-acetylcysteine attenuates lung ischemia-reperfusion injury after lung transplantation

Ann Thorac Surg. 2007 Jul;84(1):240-6; discussion 246. doi: 10.1016/j.athoracsur.2007.03.082.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Animals
  • Glutathione / analysis
  • Lipid Peroxidation
  • Lung / metabolism
  • Lung / pathology
  • Lung Transplantation / adverse effects*
  • Male
  • Peroxidase / metabolism
  • Rats
  • Rats, Inbred F344
  • Reperfusion Injury / prevention & control*
  • Superoxides / metabolism
  • Thiobarbituric Acid Reactive Substances / analysis

Substances

  • Thiobarbituric Acid Reactive Substances
  • Superoxides
  • Peroxidase
  • Glutathione
  • Acetylcysteine