HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Katsuhiko Oda Yoshikatsu Saiki Koichi Tabayashi Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kawatsu, S. Articles by Tabayashi, K. Search for Related Content PubMed PubMed Citation Articles by Kawatsu, S. Articles by Tabayashi, K. Related Collections Coronary disease

Ann Thorac Surg 2007;84:560-567
© 2007 The Society of Thoracic Surgeons

---

Original Articles: Cardiovascular

External Application of Rapamycin-Eluting Film at Anastomotic Sites Inhibits Neointimal Hyperplasia in a Canine Model

^a Department of Cardiovascular Surgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan
^b Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Science, Kyoto University, Sankyo-ku, Kyoto, Japan

Accepted for publication February 15, 2007.

^_* Address correspondence to Dr Kawatsu, Department of Cardiovascular Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan 980-8574 (Email: kawa2{at}mail.tains.tohoku.ac.jp).

Presented at the Forty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 29–31, 2007.

Background: Stenosis at a vascular anastomotic site has been a significant clinical issue. We tested the hypothesis that rapamycin-eluting biodegradable poly L-lactic acid and epsilon-caprolactone copolymer (PLA-CL) film applied externally can inhibit neointimal hyperplasia in a canine vascular anastomosis model.

Methods: Femoral artery graft interposition was performed in 25 beagles. Beagles were divided into five groups (five in each): graft interposition without PLA-CL film (control); with PLA-CL film only; and PLA-CL containing rapamycin 8 µg, 80 µg, and 800 µg. Orthotopic arterial graft interposition was performed on the left side and vein graft from the ipsilateral femoral vein was interposed on the right. Morphometric and immunochemical analyses were performed at four-week intervals.

Results: In arterial graft models, the ratio of intimal area (intimal area divided by the entire vessel area) was significantly reduced in all the three rapamycin-eluting film groups compared with control (0.19, 0.07, 0.05, and 0.38 in 8 µg, 80 µg, 800 µg groups and control, respectively, p < 0.05). In vein graft models, the ratio of intimal area was significantly decreased only in the 800 µg rapamycin group compared with control (0.33 vs 0.54, p < 0.05). Inhibition of neointimal growth was associated with reduced cell proliferation, as evidenced by proliferating cell nuclear antigen immunostaining and diminished alpha-actin positive vascular smooth muscle cells.

Conclusions: Rapamycin-eluting biodegradable PLA-CL film applied externally can inhibit neointimal hyperplasia of arterial and vein grafts in a canine model. The inhibitory effect of rapamycin-eluting film against neointimal growth is more pronounced in the arterial graft than the vein graft.

This article has been cited by other articles:

				W. D. Paulson, N. Kipshidze, K. Kipiani, N. Beridze, M. V. DeVita, S. Shenoy, and S. S. Iyer Safety and efficacy of local periadventitial delivery of sirolimus for improving hemodialysis graft patency: first human experience with a sirolimus-eluting collagen membrane (Coll-R) Nephrol. Dial. Transplant., January 11, 2012; (2012) gfr667v1. [Abstract] [Full Text] [PDF]

				S. Morizumi, Y. Suematsu, S. Gon, and T. Shimizu Inhibition of Neointimal Hyperplasia With a Novel Tacrolimus-Eluting Suture J. Am. Coll. Cardiol., July 19, 2011; 58(4): 441 - 442. [Full Text] [PDF]

				M. Desai, J. Mirzay-Razzaz, D. von Delft, S. Sarkar, G. Hamilton, and A. M. Seifalian Inhibition of neointimal formation and hyperplasia in vein grafts by external stent/sheath Vascular Medicine, August 1, 2010; 15(4): 287 - 297. [Abstract] [PDF]

				T. Rajathurai, S. I. Rizvi, H. Lin, G. D. Angelini, A. C. Newby, and G. J. Murphy Periadventitial Rapamycin-Eluting Microbeads Promote Vein Graft Disease in Long-Term Pig Vein-Into-Artery Interposition Grafts Circ Cardiovasc Interv, April 1, 2010; 3(2): 157 - 165. [Abstract] [Full Text] [PDF]

				M. Mutsuga, Y. Narita, A. Yamawaki, M. Satake, H. Kaneko, Y. Suematsu, A. Usui, and Y. Ueda A new strategy for prevention of anastomotic stricture using tacrolimus-eluting biodegradable nanofiber. J. Thorac. Cardiovasc. Surg., March 1, 2009; 137(3): 703 - 709. [Abstract] [Full Text] [PDF]

				S. Semsroth, R. G. Stigler, O. Y. Bernecker, E. Ruttmann-Ulmer, J. Troppmair, K. Macfelda, J. O. Bonatti, and G. Laufer Everolimus attenuates neointimal hyperplasia in cultured human saphenous vein grafts Eur J Cardiothorac Surg, March 1, 2009; 35(3): 515 - 520. [Abstract] [Full Text] [PDF]