title: External application of rapamycin-eluting film at anastomotic sites inhibits neointimal hyperplasia in a canine model.
abstract: 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 microg, 80 microg, and 800 microg. 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 microg, 80 microg, 800 microg groups and control, respectively, p < 0.05). In vein graft models, the ratio of intimal area was significantly decreased only in the 800 microg 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.
authors.affiliation: Department of Cardiovascular Surgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan. kawa2@mail.tains.tohoku.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawatsu
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Oda
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Saiki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Koichi
authors.initials: K
authors.lastname: Tabayashi
mesh_terms: D000714:Anastomosis, Surgical / Q000009:adverse effects*; D000818:Animals; D018441:Biofilms; D004195:Disease Models, Animal; D004285:Dogs; D005263:Femoral Artery / Q000601:surgery*; D006965:Hyperplasia / Q000188:drug therapy / Q000517:prevention & control; D020123:Sirolimus / Q000627:therapeutic use*; D017539:Tunica Intima / Q000187:drug effects / Q000503:physiopathology*; D014656:Vascular Surgical Procedures / Q000009:adverse effects*
chemical_list: D020123:Sirolimus