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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

View larger version (11K): [in a new window]   Figure 1 A, Cumulative ST638 release from PLLA stent over a 3-wk period as a percentage of the initial loaded ST638 in vitro. Each data point represents the mean of two measurements. B, Local concentration of ST638 in the porcine coronary arteries implanted with the ST638 stent at 0, 3, 7, and 21 d after stent implantation in vivo.

View larger version (73K): [in a new window]   Figure 2 Coronary angiograms in a pig. A, Before stent implantation; B, immediately after stent implantation; and C, 3 wk after stent implantation. The white arrow indicates the site implanted with ST638 stent, and the black arrow shows the site implanted with control stent.

View larger version (24K): [in a new window]   Figure 3 Angiographic coronary stenosis 3 wk after implantation with the ST638 or control stent.

View larger version (78K): [in a new window]   Figure 4 Photomicrograph of the stented coronary segments 3 wk after stent implantation. A, Neointima and media around the PLLA stent thread. I, Neointima; M, media; A, adventitia; S, stent thread (x400). B, A coronary segment implanted with the control stent (x40). C, A coronary segment implanted with the ST638 stent (x40). Calibration: 0.1 mm for A, and 1.0 mm for B and C.

View larger version (22K): [in a new window]   Figure 5 Intima/media ratio 3 wk after control or ST638 stent implantation.

View larger version (23K): [in a new window]   Figure 6 Changes in the cross-sectional areas of porcine coronary arteries 3 wk after PLLA stent implantation. The changes in the cross-sectional areas are expressed as percent changes compared with the adjacent normal coronary segment. **Significance of the changes from control (zero) level.