Effect of cilostazol, a phosphodiesterase III inhibitor, on experimental thrombosis in the porcine carotid artery.
Thrombus formation in the carotid artery is one of the common causes of transient ischemic attacks and stroke. Platelet aggregation seems to be an essential component in these processes. The present study was conducted to determine the ability of cilostazol, a phosphodiesterase III inhibitor, to prevent formation of totally occlusive thrombus in a porcine carotid artery, in comparison with ticlopidine. Castrated male Yorkshire pigs were allocated to control (n=8), cilostazol (30 mg/kg, twice a day [b.i.d] for 2 days, n=8), and ticlopidine (50 mg/kg, b.i.d. for 3 days, n=7) groups. The endothelium of the right common carotid artery was injured with electrical stimulation (150 microA) without constriction and blood flow in this region was monitored by Doppler flow probe. Arterial blood was sampled during electrical stimulation for the measurement of platelet aggregation. Total occlusion rates within 240 minutes were 87.5% (7:8), 37.5% (3:8), and 85.7% (6:7) in the control, cilostazol, and ticlopidine groups, respectively. Compared with the control group, the time to total occlusion was significantly prolonged in the cilostazol group, but not in the ticlopidine group. Consistently, platelet aggregation was significantly inhibited only in the cilostazol group. Because ticlopidine increases blood flow in the intact carotid artery before injury to a greater extent than cilostazol, direct antiplatelet action is thought to be responsible for cilostazol's beneficial effect in preventing thrombotic occlusion. These results suggest that cilostazol may be useful for the inhibition of the thrombus formation in the carotid artery and for the prevention of cerebral ischemic events.
Kohda
N
N
Tokushima Research Institute, Department of Advanced Pharmacology, Otsuka Pharmaceutical Co., Ltd., Japan.
Tani
T
T
Nakayama
S
S
Adachi
T
T
Marukawa
K
K
Ito
R
R
Ishida
K
K
Matsumoto
Y
Y
Kimura
Y
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000503:physiopathology*; D000077407:Cilostazol; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000293:injuries; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009919:Orchiectomy; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000097:blood; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood* / Q000209:etiology / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000097:blood; D013988:Ticlopidine / Q000494:pharmacology
D013777:Tetrazoles; D012701:Serotonin; D013929:Thromboxane B2; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000077407:Cilostazol; D013988:Ticlopidine