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

Background Antioxidant treatment seems to reduce the development of restenosis after percutaneous transluminal angioplasty. In this study, the effect of Nicanartine, a new antioxidant drug with both antiproliferative and lipid-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 of 48 New Zealand White rabbits, electrostimulation was carried out for 28 days. After a break of 7 days, balloon angioplasty was performed in 36 animals, of which 18 received Nicanartine at a dose of 120 mg/kg body weight; the 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, macrophage 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) reduction 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-eight days after balloon angioplasty, proliferative activity in both groups was decreased to a level comparable to the non-dilated control groups. A clear 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 levels did not differ significantly between the groups. Conclusion Under treatment with Nicanartine a clear reduction in the proliferative and inflammatory response after balloon angioplasty was observed. Antioxidant treatment, especially with compounds having antiproliferative and lipid-lowering properties, appears to be an effective secondary preventive strategy after interventional treatment in patients with coronary artery disease. Coronary Artery Dis 9:831-837 (C) 1998 Lippincott Williams & Wilkins.