Suppression of Neointimal Hyperplasia by External Application of Cilostazol-Eluting Film at Anastomotic Sites in a Canine Model

(Department of Cardiovascular Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan)

Tomoaki Kagatani Katsuhiko Oda Satoshi Kawatsu
Naotaka Motoyoshi Syunsuke Kawamoto Junetsu Akasaka
Yoshio Nitta Yoshikatsu Saiki Atsushi Iguchi
Koichi Tabayashi
Neointimal hyperplasia is the principal mechanism of graft failure in coronary artery bypass surgery. Systemic administration of cilostazol has been reported to suppress neointimal hyperplasia in some vascular injury models. We sought to deliver cilostazol locally in an attempt to augment its beneficial effect to inhibit neointimal hyperplasia at an anastomotic site. We examined whether the external application of a novel cilostazol-eluting film can inhibit neointimal hyperplasia in a vascular anastomosis model. Canine femoral artery graft interposition was performed in 20 beagle dogs, assigned to 4 groups of 5 dogs each:a graft interposition without copolymer of L-lactide and ε-caprolactone(P(LA/CL))film(control group)and groups with P(LA/CL)film containing cilostazol of either 10mg, 40mg, or 80mg doses. All the cilostazol-eluting film with 10mg, 40mg, and 80mg dose groups had a reduced intima/media ratio compared to the control group(0.15±0.03, 0.11±0.03, and 0.12±0.03, vs. 0.31±0.03, p<0.05). Immunohistochemical analyses for proliferating cell nuclear antigens revealed reduced cellular proliferating activity associated with decreased α-actin positive cells in the cilostazol-eluting film groups compared to the control group. External application of cilostazol-eluting film can inhibit neointimal hyperplasia, at least in part, by inhibiting smooth muscle cell proliferation in the intima.
  Jpn. J. Cardiovasc. Surg. 39:162-171(2010)

Keywords:neointimal hyperplasia, cilostazol, P(LA/CL), arterial graft model