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

Sang Yup Lim; Myung Ho Jeong; Doo Sun Sim; Young Joon Hong; Ju Han Kim; Youngkeun Ahn; Jeong Gwan Cho; Jong Chun Park; Jung Chaee Kang; Hyun Tae Moon; Youngro Byun

doi:10.4068/cmj.2009.45.2.87

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Lim, Jeong, Sim, Hong, Kim, Ahn, Cho, Park, Kang, Moon, and Byun: Inhibitory Effect of Double Coating with Echinomycin and Hydrophobic Heparin in a Porcine Coronary In-Stent Restenosis Model

Original Article

Chonnam Medical Journal

Chonnam Medical Journal 2009; 45(2): 87-91.

Published online: 12 August 2009

DOI: https://doi.org/10.4068/cmj.2009.45.2.87

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

Sang Yup Lim, Myung Ho Jeong¹, Doo Sun Sim¹, Young Joon Hong¹, Ju Han Kim¹, Youngkeun Ahn¹, Jeong Gwan Cho¹, Jong Chun Park¹, Jung Chaee Kang¹, Hyun Tae Moon², Youngro Byun³

The Cardiovascular Center of Korea University, Ansan Hospital, Seoul, Korea.

¹The Heart Center of Chonnam National University Hospital, Chonnam National University Research Institute of Medical Science, Gwangju, Korea.

²Mediplex Corporation, Korea.

³College of Pharmacy, Seoul National University, Seoul, Korea.

Corresponding author (myungho@chollian.net)

Accepted 29 April 2009

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 mm² in Group I, 5.7±1.3 mm² in Group II, 3.7±1.0 mm² in Group III, and 2.7±1.1 mm² 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.

Keywords: Stents, Restenosis, Thrombosis, Prevention

Figures and Tables

Fig. 1

Histopathology of pigs coronary arteries 4 weeks after stents implantation, Hematoxyline and eosin stain. (A) Group I: control (bare stent) group, (B) Group II: 1% echinomycin, (C) Group III: 5% echinomycin, (D) Group IV: 10% echinomycin, respectively.

Table 1

Quantitative coronary angiographic findings of porcine coronary arteries

Table 2

Histopathologic assessment of porcine coronary arteries after 4 weeks of stent implantation

IEL, internal elastic lamina.

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