Cilostazol suppresses neointimal hyperplasia in canine vein grafts.
OBJECTIVE
To investigate whether cilostazol, a cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor, suppresses intimal hyperplasia in canine vein grafts, and to elucidate its mechanisms in terms of cell proliferation and apoptosis.


METHODS
Bilateral reversed jugular vein interposition grafts of the common carotid artery were performed in 12 beagle dogs. Starting from 7 days before surgery, either cilostazol (30 mg/day; n = 6) or a placebo (n = 6) was given orally twice daily. Vein grafts were harvested at 1 or 4 weeks, and fixed under pressure for histological examination.


RESULTS
By 1 week after implantation, the cilostazol group showed significantly less cell proliferation than the placebo group. By 4 weeks after implantation, intimal and medial thickness was significantly thinner in the cilostazol group than in the placebo group. There was significantly more apoptosis in the placebo group than in the cilostazol group at both time points.


CONCLUSIONS
Cilostazol suppressed the development of intimal hyperplasia in canine autogenous vein grafts. Thus, it may be associated with the modulation of cell proliferation and apoptosis.
Kudo
Fabio A
FA
Department of Cardiovascular Surgery, Hokkaido University School of Medicine, Sapporo, Hokkaido, Japan.
Kondo
Yuka
Y
Muto
Akihito
A
Miyazaki
Keiko
K
Dardik
Alan
A
Nishibe
Masayasu
M
Nishibe
Toshiya
T
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D000077407:Cilostazol; D004285:Dogs; D006965:Hyperplasia / Q000188:drug therapy / Q000473:pathology; D020287:In Situ Nick-End Labeling; D023421:Models, Animal; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011897:Random Allocation; D013777:Tetrazoles / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*; D014654:Vascular Patency; D014680:Veins / Q000473:pathology* / Q000637:transplantation
D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol