N. Ishizaka et al., Effects of a single local administration of cilostazol on neointimal formation in balloon-injured rat carotid artery, ATHEROSCLER, 142(1), 1999, pp. 41-46
Citations number
30
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
To elucidate if locally administered cilostazol, an inhibitor of cyclic AMP
phosphodiesterase III, suppresses neointimal formation in balloon-injured
carotid artery of the rat, 20 mg of cilostazol was topically applied using
pluronic gel at the time of balloon injury. Rats were sacrificed 14 days af
ter balloon injury to measure the extent of neointimal formation. Plasma an
d tissue concentrations of cilostazol were also measured at 1, 3, 7 and 14
days after topical application. The 5-bromo-2'-deoxyuridine (BrdU, a thymid
ine analogue) was given intraperitoneally to detect proliferation of smooth
muscle cells in the injured media at 3 days after balloon injury. At 1 day
after injury, plasma and tissue concentrations were 0.147 +/- 0.043 mu g/m
l and 1380 mu g/g tissue. Although the plasma concentration of cilostazol w
as undetectable (< 0.02 mu g/ml), a significant amount of cilostazol (46 mu
g/g tissue) was still detected in the tissue at the site of application ev
en after 2 weeks. The intimal area of the injured carotid after 2 weeks was
significantly smaller in the cilostazol-treated group than in the gel-trea
ted control group (0.06 +/- 0.01 vs 0.15 +/- 0.02 mm(2), P < 0.001). BrdU-p
ositive smooth muscle cells in the injured media after 3 days were also sig
nificantly fewer in the cilostazol-treated group than in the gel-treated co
ntrol group (4.3 +/- 0.5 vs 9.1 +/- 0.9% of total cells, P < 0.001). These
results suggest that local administration of cilostazol using pluronic gel
maintains a high concentration of the drug at the application site, has an
anti-proliferative effect on smooth muscle cells, and may have potential fo
r clinical therapeutic use for the prevention of restenosis following arter
ial intervention. (C) 1999 Elsevier Science Ireland Ltd. All rights reserve
d.