Saniabadi A R, Fisher T C, McLaren M, Belch J F, Forbes C D
Department of Medicine, University of Dundee, Ninewells Hospital, United Kingdom.
Cardiovasc Res. 1991 Mar;25(3):177-83. doi: 10.1093/cvr/25.3.177.
The aim was to investigate the effects of dipyridamole, aspirin, and a combination of dipyridamole plus aspirin on platelet aggregation in whole blood, PGI2 generation, and red cell deformability ex vivo.
were 16 male volunteers, aged 22-39 years, mean age, 26.6 years.
This was a randomised, double blind, placebo controlled trial. The volunteer received each of the following treatments 10 days apart: dipyridamole 200 mg; aspirin 300 mg; dipyridamole 200 mg plus aspirin 300 mg; matched placebos.
Blood was taken for platelet function tests, PGI2 metabolite assay, and red cell deformability before and 2 h after the trial dose was taken. Platelet aggregation was quantified by measuring the fall in single platelet count after stimulation with 2 micrograms.ml-1 collagen or 50 nM platelet activating factor (PAF), or by rollermixing aliquots of blood to initiate spontaneous aggregation. The platelet function tests were completed at 37 degrees C within 10 min of venepuncture. The stable metabolite of PGI2, 6-keto PGF1 alpha, was measured in serum. There was inhibition of spontaneous platelet aggregation by dipyridamole (p less than 0.004), aspirin (p less than 0.005), and the combination of dipyridamole plus aspirin (p less than 0.0001) as compared with placebo. PAF induced platelet aggregation was inhibited by dipyridamole (p less than 0.002) and the combination of dipyridamole plus aspirin (p less than 0.0001) but aspirin alone had no inhibitory effect. Collagen induced platelet aggregation was inhibited by all three treatments: dipyridamole (p less than 0.06), aspirin (p less than 0.0001), and the combination of dipyridamole plus aspirin (p less than 0.0001). PGI2 generation was markedly inhibited by aspirin (p less than 0.0001) and the combination doses (p less than 0.0001) but was unaffected by dipyridamole alone. Of the three active treatments, only dipyridamole alone significantly (p less than 0.001) increased red cell deformability; there was a modest decrease in red cell deformability with aspirin.
The results with PAF support the view that dipyridamole inhibits platelet activation by more than one mechanism; the effect on collagen induced and spontaneous platelet aggregation suggests that the effect of the combination doses is additive and that on red cell deformability the synergy is negative.
旨在研究双嘧达莫、阿司匹林以及双嘧达莫与阿司匹林联合用药对全血中血小板聚集、前列环素（PGI2）生成及离体红细胞变形性的影响。
16名男性志愿者，年龄在22 - 39岁之间，平均年龄26.6岁。
这是一项随机、双盲、安慰剂对照试验。志愿者每隔10天接受以下每种治疗：双嘧达莫200毫克；阿司匹林300毫克；双嘧达莫200毫克加阿司匹林300毫克；匹配的安慰剂。
在服用试验剂量前及服用后2小时采集血液用于血小板功能测试、PGI2代谢物测定及红细胞变形性检测。通过测量用2微克/毫升胶原蛋白或50纳摩尔血小板活化因子（PAF）刺激后单个血小板计数的下降来量化血小板聚集，或通过滚动混合血样等分试样以引发自发聚集。血小板功能测试在静脉穿刺后10分钟内在37摄氏度下完成。在血清中测量PGI2的稳定代谢物6 - 酮 - PGF1α。与安慰剂相比，双嘧达莫（p < 0.004）、阿司匹林（p < 0.005）以及双嘧达莫加阿司匹林联合用药（p < 0.0001）均能抑制自发血小板聚集。双嘧达莫（p < 0.002）和双嘧达莫加阿司匹林联合用药（p < 0.0001）可抑制PAF诱导的血小板聚集，但阿司匹林单独使用无抑制作用。所有三种治疗均能抑制胶原蛋白诱导的血小板聚集：双嘧达莫（p < 0.06）、阿司匹林（p < 0.0001）以及双嘧达莫加阿司匹林联合用药（p < 0.0001）。阿司匹林（p < 0.0001）和联合用药剂量（p < 0.0001）显著抑制PGI2生成，但双嘧达莫单独使用对其无影响。在三种活性治疗中，只有双嘧达莫单独使用能显著（p < 0.001）增加红细胞变形性；阿司匹林使红细胞变形性略有下降。
PAF的研究结果支持双嘧达莫通过多种机制抑制血小板活化的观点；对胶原蛋白诱导和自发血小板聚集的作用表明联合用药剂量的效果是相加的，而对红细胞变形性的作用协同性为负。
