Intramural delivery of a specific tyrosine kinase inhibitor with biodegradable stent suppresses the restenotic changes of the coronary artery in pigs in vivo

Tohru Yamawaki, Hiroaki Shimokawa, Toshiyuki Kozai, Kenji Miyata, Taiki Higo, Eriko Tanaka, Kensuke Egashira, Tadayoshi Shiraishi, Hideo Tamai, Keiji Igaki, Akira Takeshita

研究成果: Article査読

132 被引用数 (Scopus)

抄録

Objectives. This study was designed to examine whether or not intramural delivery of ST638 (a specific tyrosine kinase inhibitor) with biodegradable stent can suppress the restenotic changes of the coronary artery in vivo. Background. Clinical and animal studies demonstrated that restenosis after coronary intervention results from a combined effect of neointimal formation and geometric remodeling (decrease in total cross-sectional area). Thus, the most effective strategy to prevent the restenosis appears to inhibit both the neointimal formation and geometric remodeling by antiproliferative agent and stent, respectively. We have previously shown that ST638 markedly suppresses the restenotic changes of the porcine coronary artery when applied from the adventitial site. Methods. A poly-L-lactic acid biodegradable stent was coated with either ST638 (0.8 mg) or equimolar of its inactive metabolite, ST494. A pair of these stents were implanted alternatively in the left anterior descending or circumflex coronary artery in pigs (n = 6). Three weeks after the procedure, coronary stenosis was assessed by angiography followed by histological examination. Results. Coronary stenosis was significantly less at the ST638 stent site than at the ST494 stent site (47 ± 5% vs. 25 ± 4%, p < 0.01). Histological examination also showed that the extent of neointimal formation and that of geometric remodeling were significantly less at the ST638 stent site than at the ST494 stent site (p < 0.05). Conclusions. These results indicate that intramural delivery of a specific tyrosine kinase inhibitor with biodegradable stent overcomes the proliferative stimuli caused by balloon injury, the stent itself, and the drug coating on the stent, resulting in the suppression of the restenotic changes of the coronary artery in vivo. This strategy might also be useful in the clinical setting in humans.

本文言語English
ページ(範囲)780-786
ページ数7
ジャーナルJournal of the American College of Cardiology
32
3
DOI
出版ステータスPublished - 1998 9月
外部発表はい

ASJC Scopus subject areas

  • 循環器および心血管医学

フィンガープリント

「Intramural delivery of a specific tyrosine kinase inhibitor with biodegradable stent suppresses the restenotic changes of the coronary artery in pigs in vivo」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル