Inhibitory Effect of Double Coating with Echinomycin and Hydrophobic Heparin in a Porcine Coronary In-Stent Restenosis Model

Abstract

Stent thrombosis and in-stent restenosis are still major limitations of coronary stenting. Here, we report on a new type of drug-eluting stent (DES) aimed to prevent restenosis and thrombosis. The DES was prepared by coating a bare metal stent with echinomycin (an anti-proliferative drug) and hydrophobic heparin. The echinomycin-hydrophobic heparin double-coating stents were compared with control stents in a porcine coronary stent restenosis model. Stent overdilation injury (stent : artery＝1.1 : 1.0) was compared in porcine coronary arteries between 4 groups: bare stent group (Group I, n=3), 1% echinomycin-heparin coating stent group (Group II, n=3), 5% echinomycin-heparin coating stent group (Group III, n=3), and 10% echinomycin-heparin coating stent group (Group IV, n=3). Follow-up quantitative coronary angiography was performed 4 weeks after the stents were inserted. The histopathologic assessments of the stented porcine coronary arteries were compared between the 4 groups. The neointimal areas of the stented arteries were 4.3±1.3 mm 2 in Group I, 5.7±1.3 mm 2 in Group II, 3.7±1.0 mm 2 in Group III, and 2.7±1.1 mm 2 in Group IV; the neointimal area was significantly larger in Group II than in the other groups (p＜0.001). The histopathologic areas of stenosis were 61.4±18.1% in Group I, 79.8±24.0% in Group II, 52.0±18.5% in Group III, and 30.9±14.6% in Group IV; the histopathologic area was significantly smaller in Group IV than in the other groups (p＜0.001). In conclusion, echinomycin-hydrophobic heparin double-coating stents effectively inhibit neointimal proliferation at a relatively high level.