Prevention of primary graft dysfunction in lung transplantation by N-acetylcysteine after prolonged cold ischemia.
BACKGROUND
N-Acetylcysteine (NAC), a thiol-containing compound that has been used as an anti-oxidant, may also lead to an increased glutathione synthesis. This study assessed the protective effect of NAC on primary graft dysfunction after lung transplantation.


METHODS
Porcine single left-lung transplantation was performed in 2 experimental groups after 24 hours of cold storage. Donor and recipient animals were treated with intravenous injection of 150 mg/kg NAC 60 minutes before harvest and reperfusion, followed by 12.5 mg/kg/hour continuous perfusion during the 8-hour observation period (NAC). Control animals did not receive any treatment. Hemodynamic and respiratory parameters were recorded throughout the observation period. Bronchoalveolar lavage (BAL) nitrite, neutrophil elastase (NE), protein accumulation, interleukin (IL)-8, nuclear factor-κB (p50 sub-unit), and reduced glutathione (GSH) in lung tissue and red blood were measured.


RESULTS
During the observation period, the mean pulmonary artery pressure, oxygenation, airway pressure, and static lung compliance were significantly better in NAC animals compared with controls (p < 0.05). Extravascular lung water index was higher at points during the reperfusion in the control group. BAL protein, nitrite, NE, and IL-8 cytokine levels at the end of the experiment were significantly higher in the controls than in the NAC group (p < 0.05). Lung tissue reduced GSH levels were significantly higher in the NAC group than in the control group. Red blood cell GSH levels were always higher in the NAC group during the reperfusion period. Reverse transcription polymerase chain reaction for IL-8 messenger RNA was significantly higher in controls during the reperfusion period than in the NAC group (p = 0.001). The amount of lung tissue nuclear NF-κB (p50 sub-unit) was significantly higher in controls than in NAC pigs (p = 0.03).


CONCLUSIONS
In this model, donor and recipient treatment with NAC effectively protected the lung from primary graft dysfunction after prolonged cold ischemia.
Inci
Ilhan
I
Division of Thoracic Surgery, University of Zurich, Rämistrasse 100, Zurich, Switzerland. ilhan.inci@usz.ch
Erne
Barbara
B
Arni
Stephan
S
Jungraithmayr
Wolfgang
W
Inci
Demet
D
Hillinger
Sven
S
Vogt
Peter
P
Leskosek
Boris
B
Weder
Walter
W
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D050377:Cold Ischemia / Q000009:adverse effects*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D008168:Lung / Q000378:metabolism / Q000601:surgery; D016040:Lung Transplantation; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D055031:Primary Graft Dysfunction / Q000378:metabolism / Q000517:prevention & control*; D013552:Swine
D016166:Free Radical Scavengers; D016328:NF-kappa B; D009569:Nitric Oxide; D005978:Glutathione; D000111:Acetylcysteine