N-acetyl cysteine pre-treatment attenuates inflammatory changes in the warm ischemic murine lung.
BACKGROUND
The warm ischemic period in non-heart-beating donor lungs may contribute to a higher degree of ischemia-reperfusion injury after lung transplantation. We investigated the impact and timing of administration of N-acetyl cysteine (NAC) on inflammatory parameters.


METHODS
Ischemia (I) was induced by clamping the hilum of the left lung for 90 minutes, and some protocols were followed by reperfusion (R) for 4 hours. Mice were divided into nine groups (n = 6/group): three control groups ([sham] (thoracotomy only), [I] and [I+R]); two groups with saline instillation only ([saline+I] and [saline+I+R]); and four experimental groups with NAC (50 mg/kg), administered by instillation ([NAC+I], [NAC+I+R] and [I+NAC+R]) or by aerosol ([NACaero+I+R]). Cell counts and protein levels in bronchoalveolar lavage (BAL) were determined.


RESULTS
NAC administered prior to hilar clamping led to a significant decrease in macrophages and lymphocytes and interleukin (IL)-1 beta levels after ischemia. NAC also resulted in significantly fewer macrophages, lymphocytes and neutrophils as well as IL-1 beta, keratinocyte cytokine (KC), monocyte chemoattractant protein (MCP)-1 and IL-6 levels in BAL taken after reperfusion.


CONCLUSIONS
NAC treatment prior to warm ischemia attenuates inflammatory changes after both the ischemic and reperfusion periods.
Geudens
Nele
N
Laboratory of Experimental Thoracic Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.
Van De Wauwer
Caroline
C
Neyrinck
Arne P
AP
Timmermans
Lien
L
Vanhooren
Hadewijch M
HM
Vanaudenaerde
Bart M
BM
Verleden
Geert M
GM
Verbeken
Erik
E
Lerut
Toni
T
Van Raemdonck
Dirk E M
DE
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D001706:Biopsy; D018893:Bronchoalveolar Lavage; D002452:Cell Count; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D016040:Lung Transplantation / Q000379:methods / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D052096:Warm Ischemia / Q000009:adverse effects*
D018925:Chemokines; D016207:Cytokines; D016166:Free Radical Scavengers; D036341:Intercellular Signaling Peptides and Proteins; D000111:Acetylcysteine