Antithrombotic Effect of Ticlopidine on He-Ne Laser-Induced Thrombus Formation in Rat Mesenteric Microvessels

Clopidogrel is a new thienopyridine derivative similar to ticlopidine, which inhibits adenosine diphosphate-induced platelet aggregation. The in vitro effects of clopidogrel on shear-induced platelet activation and coagulation were assessed after oral administration to rats, by subjecting non-anticoagulated blood to haemostatometry. Clopidogrel significantly inhibited shear-induced platelet activation and coagulation 2 h after administration at doses of 7.5 and 15 mg/kg. Both ticlopidine (200 mg/kg) and aspirin (200 mg/kg) inhibited shear-induced platelet activation, but not coagulation. The peak inhibition of plaetelet activation by clopidogrel occurred 2 h after oral administration, but significant inhibition persisted even after 24 h. These results suggest that clopidogrel could be a more potent antithrombotic agent than ticlopidine or aspirin, and also that ADP plays an important role in shear-induced platelet activation.

Section: Discussionsupporting

confidence: 87%

Effects of Clopidogrel on Platelet Activation and Coagulation of Non-Anticoagulated Rat Blood under High Shear Stress

Taka

Okano

Seki

et al. 1999

“…The duration of the anti thrombotic effect of argatroban appeared to be longer in venules than in arterioles, and the results might reflect differences in the throm botic potential between the different micro vessels. A differential antithrombotic effect in mesenteric arterioles has also been observed after administration of acetylsalicylic acid [ 12].…”

Section: Discussionmentioning

confidence: 90%

“…Thrombi induced by an argon laser are easily disrupted by flow ing blood, and occlusive thrombi are rarely formed [7]. In contrast, thrombi formed with a He-Ne laser are usually completely occlu sive, and this method offers significant ad vantages for the study of thrombosis in situ [9][10][11][12],…”

Section: Introductionmentioning

confidence: 99%

Antithrombotic Effect of Argatroban on the Pial Vessels of the Rat: A Study with He-Ne Laser-Induced Thrombus Formation

Sasaki

Morii

Yamashita

et al. 1993

Self Cite

The antithrombotic effect of the synthetic thrombin inhibitor (2R,4R)-4-methyl-1 -[N²-(3-methyl-1,2,3,4-tetrahydro-8-quin-olinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid mono-hydrate (argatroban) was investigated in cerebral vessels of the rat. An occlusive thrombus was formed in pial vessels using a He-Ne laser in a closed cranial window technique. Argatroban retarded the formation of thrombi in a dose-dependent manner. The antithrombotic effect of a single intravenous dose of argatroban at 0.5 mg/kg was diminished after 30 min in arterioles and after 50 min in venules, respectively. The antithrombotic activity was maintained, however, by continuous intravenous infusion (2 mg/kg/h).

“…For example the results of the Ticlopidine and Aspirin Stroke Study (TASS) indicated that both drugs were effective in the primary and secondary pre vention of stroke but that ticlopidine might have been more effective than ASA in these instances [12][13][14][15][16]. In addition, we have pre viously demonstrated that ticlopidine had a greater antithrombotic activity than ASA in an in vivo animal model using mesenteric microvessels [22], In the present study we compared ticlopidine and L-ASA in an in vivo model, using cerebral microvessels, and L-ASA showed as strong an antithrombotic effect as ticlopidine. The current results tended to indicate that L-ASA was more effec tive than ASA, since ASA inhibited thrombus formation only in mesenteric arterioles at 300 mg/kg and failed to inhibit it in venules in the previous study [22],…”

Section: Discussionmentioning

confidence: 99%

“…Microthrombi were formed using a He-Ne laser operated at a power of 20 mW (Nco-30 MS; Nihon Kagaku Eng., Osaka, Japan) in the presence of Evans blue [18,22], The laser beam was introduced into the operating microscope by a dichroic mirror and was directed through the optical path to the center of the microvessels. The diameter of the laser spot on the focal plane was 35 pm.…”

Section: Laser-induced Thrombus Formationmentioning

confidence: 99%

Protective Effects of Ticlopidine and Aspirin, Administered Alone and in Combination, on Thrombus Formation in Rat Cerebral Vessels

Sasaki

Ishii²,

Giddings³

et al. 1996

The protective effects of ticlopidine and d, l-lysine acetylsalicylate (L-ASA), used alone and in combination, on the pathogen-esis of thrombosis in cerebral blood vessels were investigated in a rat animal model using a He-Ne laser method. Ticlopidine and L-ASA, given orally at a concentration from 100 mg/kg, inhibited thrombus formation in a dose-dependent manner. Ticlopidine (300 mg/kg p.o.) inhibited thrombosis in arterioles and venules for 3 days after administration. The inhibitory activity of L-ASA (300 mg/kg p.o.) was less prolonged than that of ticlopidine and was observed for only approximately 24 h. Combined administration of ticlopidine and L-ASA significantly enhanced and prolonged the antithrombotic effects of either drug given alone. The results demonstrate that ticlopidine and L-ASA have potent antithrombotic properties in rat cerebral blood vessels in vivo.