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

Inci I, Zhai W, Arni S, Hillinger S, Vogt P, Weder W

Division of Thoracic Surgery, University of Zurich, Zurich, Switzerland.

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.

Published 25 June 2007 in Ann Thorac Surg, 84(1): 240-6; discussion 246.
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