Effect of the antioxidant Nicanartine on the proliferative and inflammatory response after experimental balloon angioplasty

Background Antioxidant treatment seems to reduce the development of resteno sis after percutaneous transluminal angioplasty. In this study, the effect of Nicanartine, a new antioxidant drug with both antiproliferative and lipi d-lowering properties, on the proliferative and inflammatory response after balloon angioplasty was investigated in a rabbit model of restenosis. Methods To induce pre-interventional plaques in the common carotid artery o f 48 New Zealand White rabbits, electrostimulation was carried out for 28 d ays. After a break of 7 days, balloon angioplasty was performed in 36 anima ls, of which 18 received Nicanartine at a dose of 120 mg/kg body weight; th e other 18 served as a control group. The vessels were excised by day 7 and 28 after balloon angioplasty and examined for intimal plaque size, macroph age content and proliferative activity, Bromodeoxyuridine labeling was used to determine proliferating cells in the dilated segment; macrophages were detected using the RAM-11 antibody. Results In the Nicanartine-treated group, immunohistological quantification 7 days after intervention showed a statistically significant (P < 0.05) re duction of both cells undergoing DNA synthesis (1.6 +/- 1.4% versus 3.7 +/- 2.2%) and intimal macrophages (0.7 +/- 1.2% versus 1.3 +/- 0.6%). Twenty-e ight days after balloon angioplasty, proliferative activity in both groups was decreased to a level comparable to the non-dilated control groups. A cl ear trend towards smaller plaques could be seen in the Nicanartine group (0 .146 +/- 0.077 mm(2) versus 0.255 +/- 0.174 mm(2)). Total cholesterol level s did not differ significantly between the groups. Conclusion Under treatment with Nicanartine a clear reduction in the prolif erative and inflammatory response after balloon angioplasty was observed. A ntioxidant treatment, especially with compounds having antiproliferative an d lipid-lowering properties, appears to be an effective secondary preventiv e strategy after interventional treatment in patients with coronary artery disease. Coronary Artery Dis 9:831-837 (C) 1998 Lippincott Williams & Wilki ns.