N-acetyl-cysteine in the prevention of vascular restenosis after percutaneous balloon angioplasty.
BACKGROUND
Vascular inflammation generating oxidized metabolites at the site of balloon angioplasty is believed to play a major role in the process of vessel restenosis. Glutathione, the most potent endogenous antioxidant, may have protective effects after angioplasty by suppressing local inflammatory response. The aim of the study was to test the hypothesis that oral administration of N-acetyl-cysteine (NAC, a precursor of glutathione) reduces restenosis in an animal model of vascular injury.


METHODS
In New Zealand white rabbits, an atherosclerotic lesion was introduced to both iliac arteries by air denudation of the endothelium while feeding the animals a high-cholesterol diet. After 4 weeks, all animals underwent balloon angioplasty of the endothelial injury site and half of the group was started on 150 mg/kg NAC per day. Quantitative angiography was performed prior to the angioplasty and at the final procedure 3 weeks later. Glutathione levels were determined in all animals at the beginning and the end of the study.


RESULTS
Although not statistically significant, plasma glutathione level increased in the NAC group from 32.4+/-4.4 to 39.7+/-11.6 micromol/l, while it decreased from 30.6+/-13.4 to 28.3+/-11.5 micromol/l in the control group. During the study period, 6 vessels occluded leaving 14 vessels for analysis. Quantitative angiographic analyses prior to angioplasty and at follow-up showed no significant difference with respect to stenosis progression between the groups. Measurement of neointima formation by histology showed also no significant difference between the groups (0.175+/-0.040 mm(2) vs. 0.123+/-0.075 mm(2)), neither did intimal macrophage count as a marker for local inflammatory response.


CONCLUSIONS
Despite an increase in plasma glutathione level in the NAC-treated group, there was no reduction in lesion progression after balloon angioplasty. Therefore, NAC does not seem to prevent restenosis after vascular intervention in this animal model.
Jeremias
Allen
A
Department of Internal Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA. ajeremia@bidmc.harvard.edu
Dusa
Cristian
C
Forudi
Farhad
F
Jacobsen
Donald W
DW
Vince
D Geoffrey
DG
Nissen
Steven E
SE
Tuzcu
E Murat
EM
D000111:Acetylcysteine / Q000494:pharmacology*; D000800:Angioplasty, Balloon; D000818:Animals; D003545:Cysteine / Q000097:blood; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000097:blood; D007083:Iliac Artery / Q000473:pathology; D007150:Immunohistochemistry; D011446:Prospective Studies; D011817:Rabbits; D014654:Vascular Patency / Q000187:drug effects*
D016166:Free Radical Scavengers; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine