Effects of L-arginine supplementation on endothelial function after stent implantation.

Background: In-stent restenosis after percutaneous coronary intervention (PCI) is due to the proliferation of intima. Supplementation with L-arginine has been shown to improve endothelial function and decrease neointima proliferation in experimental animal model of restenosis.

Aim: To assess the effects of L-arginine supplementation on neointima proliferation and endothelial markers as well as growth factor levels in patients after stent implantation.

Methods: In this prospective, randomised, double-blind, placebo-controlled study 60 patients undergoing stent implantation received placebo or L-arginine (200 mg/kg infused intravenously over 4 hours, 12 and 3 hours before PCI, and 500 mg over 10 minutes prior to stent implantation, followed by oral supplementation of 6 g/day for 14 days after PCI). Quantitative coronary angiography (QCA) and intracoronary ultrasonography (ICUS) were performed at baseline and after a seven-month follow-up period. Serum concentration of L-arginine was measured at baseline, before PCI, 24 hours after PCI, and 7 as well as 14 days after PCI. The transforming growth factor-beta (TGF-beta), vascular endothelial growth factor (VEGF) and endothelin levels were assessed before PCI, and 24 hours as well as 14 days after the procedure.

Results: No significant differences in the QCA or ICUS parameters were found between patients receiving L-arginine or placebo. 24 hours after stent implantation patients who received placebo had significantly a higher increase in the endothelin serum concentration and a lower rise in the VEGF level than the patients who received L-arginine (92.6+/-49 pg/ml vs 76.1+/-27 pg/ml, p<0.05, and 10 pg/ml vs 17.6+/-12 pg/ml, p<0.05, respectively). The TGF-beta level, assessed 14 days after PCI, was significantly higher in the placebo group than in the L-arginine group (14.8+/-10 ng/ml vs 11.2+/-6.1 ng/ml, p<0.05).

Conclusions: In spite of favourable changes in the vascular endothelial biochemical marker profile, supplementation with L-arginine did not decrease the in-stent reocclusion rate.