Gresele P, Zoja C, Deckmyn H, Arnout J, Vermylen J, Verstraete M
Thromb Haemost. 1983 Dec 30;50(4):852-6.
Dipyridamole possesses antithrombotic properties in the animal and in man but it does not inhibit platelet aggregation in plasma. We evaluated the effect of dipyridamole ex vivo and in vitro on platelet aggregation induced by collagen and adenosine-5'-diphosphate (ADP) in human whole blood with an impedance aggregometer. Two hundred mg dipyridamole induced a significant inhibition of both ADP- and collagen-induced aggregation in human blood samples taken 2 hr after oral drug intake. Administration of the drug for four days, 400 mg/day, further increased the antiplatelet effect. A significant negative correlation was found between collagen-induced platelet aggregation in whole blood and dipyridamole levels in plasma (p less than 0.001). A statistically significant inhibition of both collagen (p less than 0.0025) and ADP-induced (p less than 0.005) platelet aggregation was also obtained by incubating whole blood in vitro for 2 min at 37 degrees C with dipyridamole (3.9 microM). No such effects were seen in platelet-rich plasma, even after enrichment with leukocytes. Low-dose adenosine enhanced in vitro inhibition in whole blood. Our results demonstrate that dipyridamole impedes platelet aggregation in whole blood by an interaction with red blood cells, probably involving adenosine.
双嘧达莫在动物和人体中均具有抗血栓形成特性,但它并不抑制血浆中的血小板聚集。我们使用阻抗聚集仪评估了双嘧达莫在体外和体内对人全血中胶原蛋白和5'-二磷酸腺苷(ADP)诱导的血小板聚集的影响。口服200毫克双嘧达莫后2小时采集的人血样本中,ADP和胶原蛋白诱导的聚集均受到显著抑制。每天服用400毫克药物,持续四天,可进一步增强抗血小板作用。全血中胶原蛋白诱导的血小板聚集与血浆中双嘧达莫水平之间存在显著负相关(p<0.001)。将全血在37℃下与双嘧达莫(3.9微摩尔)体外孵育2分钟,也能获得对胶原蛋白(p<0.0025)和ADP诱导(p<0.005)的血小板聚集的统计学显著抑制。即使在富含白细胞的情况下,在富血小板血浆中也未观察到此类作用。低剂量腺苷增强了全血中的体外抑制作用。我们的结果表明,双嘧达莫通过与红细胞相互作用阻碍全血中的血小板聚集,可能涉及腺苷。