在人体体外系统中通过血栓素受体拮抗作用抑制血小板与血管壁的相互作用：增强阿司匹林的抗血小板作用

Inhibition of platelet-vessel wall interactions by thromboxane receptor antagonism in a human in vitro system: potentiation of antiplatelet effects of aspirin.

作者信息

Escolar G, Albors M, Garrido M, Bioque G, Díaz Ricart M, Carretero M, Ordinas A

机构信息

Servicio de Hemoterapia y Hemostasia, IDIBAPS, Hospital Clínic, Barcelona, Spain.

出版信息

Eur J Clin Invest. 1998 Jul;28(7):562-8. doi: 10.1046/j.1365-2362.1998.00327.x.

DOI:10.1046/j.1365-2362.1998.00327.x

PMID:9726037

Abstract

BACKGROUND

Pharmacological inhibition of arachidonic acid metabolism has proven therapeutically useful in the prevention of cardiovascular events.

METHODS

We have investigated the ability of Bay u 3405, a synthetic thromboxane antagonist, to interfere with platelet aggregation and arachidonic acid metabolism. The antiplatelet action was also analysed in a perfusion system in which vascular subendothelium was exposed to circulating human blood (10 min; shear rate = 800 s-1). Platelet interactions were morphometrically analysed and results compared with those obtained in studies with blood from donors taking aspirin (acetylsalicylic acid, ASA) (500 mg day-1). The additional effect of Bay u 3405 on the antiplatelet action of ASA was also evaluated.

RESULTS

Bay u 3405 caused a dose-dependent inhibition of platelet aggregation induced by U46619 with a maximal effect at concentrations > or = 0.01 microgram mL-1. Higher concentrations (> or = 0.05 micrograms mL-1) also inhibited aggregations induced by ADP or collagen. Bay u 3405 did not interfere with platelet arachidonic acid metabolism. In perfusion studies, Bay u 3405 (0.01 microgram mL-1) significantly decreased the total surface of the vessel covered by platelets (%CS = 18.7 +/- 1.09 vs. 24.4 +/- 1.94; P < 0.05) and the formation of large aggregates %T = 7.5 +/- 0.87 vs. 19.3 +/- 1.61; P < 0.01). ASA treatment reduced platelet aggregate formation (%T = 13.7 +/- 2.06; P < 0.05) but did not affect the total surface covered by platelets. The in vitro addition of Bay u 3405 to blood from ASA-treated donors further reduced the formation of large aggregates (%T = 2.7 +/- 0.79; P < 0.01 vs. ASA).

CONCLUSIONS

In vitro effect of Bay u 3405 on platelet function were superior to those observed with ASA. The thromboxane antagonism antagonism provided by Bay u 3405 further enhanced the inhibition of platelet aggregate formation found after ASA treatment.

摘要

背景

花生四烯酸代谢的药理学抑制作用已被证明在预防心血管事件方面具有治疗作用。

方法

我们研究了合成血栓素拮抗剂Bay u 3405干扰血小板聚集和花生四烯酸代谢的能力。还在一个灌注系统中分析了其抗血小板作用，在该系统中血管内皮暴露于循环的人体血液中（10分钟；剪切速率 = 800秒-1）。对血小板相互作用进行形态计量分析，并将结果与服用阿司匹林（乙酰水杨酸，ASA）（500毫克/天）的供体血液研究结果进行比较。还评估了Bay u 3405对ASA抗血小板作用的额外影响。

结果

Bay u 3405对U46619诱导的血小板聚集产生剂量依赖性抑制，在浓度≥0.01微克/毫升时达到最大效应。更高浓度（≥0.05微克/毫升）也抑制ADP或胶原诱导的聚集。Bay u 3405不干扰血小板花生四烯酸代谢。在灌注研究中，Bay u 3405（0.01微克/毫升）显著降低了血小板覆盖的血管总表面积（%CS = 18.7±1.09对24.4±1.94；P < 0.05）和大聚集体的形成（%T = 7.5±0.87对19.3±1.61；P < 0.01）。ASA治疗减少了血小板聚集体的形成（%T = 13.7±2.06；P < 0.05），但不影响血小板覆盖的总表面积。在体外将Bay u 3405添加到ASA治疗的供体血液中，进一步减少了大聚集体的形成（%T = 2.7±0.79；与ASA相比，P < 0.01）。