Locally applied cilostazol suppresses neointimal hyperplasia and medial thickening in a vein graft model.
BACKGROUND
Pathological changes in vein grafts begin immediately after arterial circulation is applied to the grafts. Chemical mediator stimulation and mechanical strain induce neointimal hyperplasia and medial thickening of the vein grafts, resulting in their failure. We investigated the inhibitory effect of locally applied cilostazol, an inhibitor of cyclic adenosine monophosphate phosphodiesterase III, on neointimal hyperplasia and medial thickening of the grafts.


RESULTS
We established a distal anastomotic stricture model of femoral vein-abdominal aorta interposition grafting in rats. In this model, neointimal hyperplasia was observed not only at the distal anastomotic sites, but also in the graft body at postoperative day 14 and was markedly progressed at day 28. A strong expression of tenascin-C was found in the media and neointima of the graft body. In the grafts around which cilostazol was administered locally using Pluronic gel, neointimal hyperplasia was significantly suppressed compared with control grafts treated with the gel alone, with the mean neointimal cross-sectional area reduced by 87.1% for the graft body and by 78.9% for the distal anastomotic sites and mean medial cross-sectional area of the graft body reduced by 54.2% at day 28 versus the control. Cilostazol treatment decreased cell proliferation and the number of tenascin-C-producing cells seen by in situ hybridization, but the expression of tenascin-C protein was not suppressed.


CONCLUSIONS
We concluded that a single perivascular application of cilostazol inhibits neointimal hyperplasia and medial thickening of vein grafts in a rat model.
Yamamoto
Kiyohito
K
Department of Thoracic and Cardiovascular Surgery, Mie University Graduate School of Medicine, Tsu, Japan.
Onoda
Koji
K
Sawada
Yasuhiro
Y
Fujinaga
Kazuya
K
Imanaka-Yoshida
Kyoko
K
Yoshida
Toshimichi
T
Shimpo
Hideto
H
D000287:Administration, Topical; D000704:Analysis of Variance; D000818:Animals; D000077407:Cilostazol; D005268:Femoral Vein / Q000187:drug effects*; D005782:Gels; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D023421:Models, Animal; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects* / Q000473:pathology
D005782:Gels; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol