CLINICAL STUDIES
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, MD*,
Hiroaki Shimokawa, MD*,
Toshiyuki Kozai, MD*,
Kenji Miyata, MD*,
Taiki Higo, MD*,
Eriko Tanaka, MD*,
Kensuke Egashira, MD*,
Tadayoshi Shiraishi, PhD ,
Hideo Tamai, MD ,
Keiji Igaki and
Akira Takeshita, MD, FACC*
* Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan
Takasago Research Laboratories, Research Institute, Kaneka Corporation, Takasago, Japan
Shiga Medical Center for Adults, Moriyama, Shiga, Japan
Igaki Medical Planning, Kyoto, Japan
Manuscript received February 2, 1998;
revised manuscript received April 29, 1998,
accepted May 13, 1998.
Address for correspondence: Dr. Hiroaki Shimokawa, Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
shimo{at}cardiol.med.kyushu-u.ac.jp
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.
|
Abbreviations and Acronyms
| | EGF | = epidermal growth factor | | EEL | = external elastic lamina | | HPLC | = high-performance liquid chromatography | | IEL | = internal elastic lamina | | IL-1ß | = interleukin-1 beta | | PDGF | = platelet-derived growth factor | | PLLA | = poly-L-lactic acid | | PTCA | = percutaneous transluminal coronary angioplasty |
|
This article has been cited by other articles:
|
|
|
|
 
M Maeng, L O Jensen, E Falk, H R Andersen, and L Thuesen
Negative vascular remodelling after implantation of bioabsorbable magnesium alloy stents in porcine coronary arteries: a randomised comparison with bare-metal and sirolimus-eluting stents
Heart,
February 1, 2009;
95(3):
241 - 246.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Vogt, A. Stein, G. Rettemeier, N. Krott, R. Hoffmann, J. v. Dahl, A.-K. Bosserhoff, W. Michaeli, P. Hanrath, C. Weber, et al.
Long-term assessment of a novel biodegradable paclitaxel-eluting coronary polylactide stent
Eur. Heart J.,
August 1, 2004;
25(15):
1330 - 1340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Lee, B. R. Wamhoff, L. C. Katwa, H. K. Reddy, D. J. Voelker, J. L. Dixon, and M. Sturek
Increased Endothelin-Induced Ca2+ Signaling, Tyrosine Phosphorylation, and Coronary Artery Disease in Diabetic Dyslipidemic Swine Are Prevented by Atorvastatin
J. Pharmacol. Exp. Ther.,
July 1, 2003;
306(1):
132 - 140.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Sousa, P. W. Serruys, and M. A. Costa
New Frontiers in Cardiology: Drug-Eluting Stents: Part II
Circulation,
May 13, 2003;
107(18):
2383 - 2389.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. N. Babapulle and M. J. Eisenberg
Coated Stents for the Prevention of Restenosis: Part I
Circulation,
November 19, 2002;
106(21):
2734 - 2740.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M Peuster, P Wohlsein, M Brugmann, M Ehlerding, K Seidler, C Fink, H Brauer, A Fischer, and G Hausdorf
A novel approach to temporary stenting: degradable cardiovascular stents produced from corrodible metal---results 6-18 months after implantation into New Zealand white rabbits
Heart,
November 1, 2001;
86(5):
563 - 569.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Sriram and C. Patterson
Cell Cycle in Vasculoproliferative Diseases : Potential Interventions and Routes of Delivery
Circulation,
May 15, 2001;
103(19):
2414 - 2419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yamasaki, K. Miyoshi, N. Oda, M. Watanabe, H. Miyake, J. Chan, X. Wang, L. Sun, C. Tang, G. McMahon, et al.
Weekly Dosing With the Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitor SU9518 Significantly Inhibits Arterial Stenosis
Circ. Res.,
March 30, 2001;
88(6):
630 - 636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Colombo and E. Karvouni
Biodegradable Stents : "Fulfilling the Mission and Stepping Away"
Circulation,
July 25, 2000;
102(4):
371 - 373.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Tamai, K. Igaki, E. Kyo, K. Kosuga, A. Kawashima, S. Matsui, H. Komori, T. Tsuji, S. Motohara, and H. Uehata
Initial and 6-Month Results of Biodegradable Poly-l-Lactic Acid Coronary Stents in Humans
Circulation,
July 25, 2000;
102(4):
399 - 404.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S Ettenson and E. R Edelman
Local drug delivery: an emerging approach in the treatment of restenosis
Vascular Medicine,
May 1, 2000;
5(2):
97 - 102.
[Abstract]
[PDF]
|
|
|
|
