Effects of cilostazol and k-134 on reconstructive surgery using prosthetic grafts in the abdominal aorta of beagle dogs.
Problems associated with prosthetic graft replacement are stenosis at the anastomosis site and thrombus formation on the inner surface. Cilostazol is known to have antiplatelet activity and inhibit vascular smooth muscle cell proliferation and neointima thickening. A cilostazol derivative, (-)-6-[3-[3-cyclopropyl-3-[(1R,2R)-2-hydroxycyclohexyl]ureido]-propoxy]-2-(1H)-quinolinone (K-134), has more potent anti-platelet activity and anti-neointimal thickening activity than cilostazol in the in-vitro platelet aggregation and in-vivo anti-hyperplastic activity assay. The aim of this study was to investigate effects of cilostazol and K-134 on thrombus formation and neointimal thickening at the site of prosthetic graft replacement. Beagle dogs underwent infrarenal abdominal aortic resection with straight Dacron graft replacement, which were allocated to the control, cilostazol, and K-134 groups. Two dogs were dead without confirming the cause of death. After 6 months, all dogs were necropsied. All prosthetic grafts were patent in each group. Ratios of red thrombus to prosthetic graft area were 0.3+/-6.4%, and 3.3+/-4.5% in the cilostazol and K-134 groups, respectively, which were significant different from that in the control group (24.4+/-16.8%). However, no clear difference was seen among the 3 groups with respect to neointimal thickness (control group, 0.70+/-0.13 mm; cilostazol group, 0.59+/-0.14 mm; K-134 group, 0.67+/-0.14 mm). Cilostazol and K-134 significantly inhibited thrombus formation on the inner surface of the prosthetic graft at 6 months after graft replacement. Neointimal thickening on the inner surface was slight even in control-group animals, and the effects of cilostazol and K-134 on such thickening were unclear.
Inoue
Yoshinori
Y
Department of Vascular and Applied Surgery, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima Bukyo-ku, Tokyo, 113-8519 Japan. yoshi.inoue.srg1@tmd.ac.jp
Sugano
Norihide
N
Jibiki
Masatoshi
M
Kudo
Toshifumi
T
Iwai
Takehisa
T
D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery*; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects*; D000077407:Cilostazol; D008297:Male; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011183:Postoperative Complications / Q000517:prevention & control; D011804:Quinolines / Q000494:pharmacology*; D019651:Plastic Surgery Procedures / Q000009:adverse effects*; D013537:Sutures; D013777:Tetrazoles / Q000494:pharmacology*; D013927:Thrombosis / Q000517:prevention & control*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D011804:Quinolines; D013777:Tetrazoles; D014508:Urea; C116725:OPC 33509; D000077407:Cilostazol