Comparative antiplatelet effects of aspirin, vapiprost and GR144053, a GPIIb/IIIa antagonist, with a special reference to the role of platelet microaggregates.
Microthrombi produced have a potential to form larger thrombi, leading to vascular occlusions. Recently, a new device to easily detect microaggregates using laser-light scattering (LS) has been developed. We adopted this device to comparatively evaluate the inhibitory effects of aspirin (1,3 or 10 mg kg(-1)), vapiprost (0.3, 1 or 3 mg kg(-1)) or GR144053 (0.1, 0.3 or 1 mg kg(-1)) on ex vivo aggregation of hamster platelets in relation to their in vivo antithrombotic effects. A transluminal thrombus was produced in the hamster femoral artery by the photochemical reaction. Each compound was injected i.v. as a bolus 10 min prior to the reaction, showing a dose-dependent antithrombotic effect, i.e. they prolonged the time before the artery occluded. At that time cyclic flow reductions occurred more marked when aspirin or vapiprost was given. At the end of experiments, blood was collected to evaluate the platelet aggregation using both the new LS device and the conventional optical density (OD) method. Many more small aggregates were still formed when the highest dose of aspirin or vapiprost was used as compared with that of GR144053, although suppression of the platelet aggregation using the OD method, prolongation of the occlusion time and the bleeding time were quite similar. In conclusion, a GPIIb/IIIa antagonist markedly suppressed the microthrombi and reduced the cyclic flow reduction. This further indicates the importance of small aggregates as triggers of thrombosis and shows that prevention of their formation may result in improved vascular patency after thrombotic insult.
Matsuno
H
H
Department of Pharmacology, Gifu University School of Medicine, Japan. leuven@cc.gifu-u.ac.jp
Kozawa
O
O
Nagashima
S
S
Kanamaru
M
M
Uematsu
T
T
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D006224:Cricetinae; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000209:etiology
D001713:Biphenyl Compounds; D005343:Fibrinolytic Agents; C090662:GR 144053; D006538:Heptanoic Acids; D010879:Piperazines; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C060013:vapiprost; D001241:Aspirin