Rao G H, Johnson G J, Reddy R K, White J G
Prostaglandins. 1981 Nov;22(5):761-72. doi: 10.1016/0090-6980(81)90215-x.
A single dose of oral aspirin in human subjects inhibits the aggregation response of platelets to arachidonate and other agents for approximately one week after ingestion. In the present study we have evaluated the rate at which cyclo-oxygenase active platelets return to the circulation in humans and dogs and compared the response curves obtained to improvements in cyclo-oxygenase activity produced by the aspirin platelets. After a single dose of aspirin, dog platelet function was compromised for several days. Normal responses to arachidonate and other aggregating agents were restored six days after aspirin, and the pattern of recovery was the same for dogs and human subjects. However, cyclo-oxygenase active platelets returned to the circulation in dogs more rapidly than in humans and chemical competence was restored in both species well before correction of the defective response to aggregating agents. The delay of 1-3 days before return of significant numbers of cyclo-oxygenase active platelets most likely reflects acetylation of bone marrow megakaryocytes by the drug. More rapid return of chemically competent cells in dogs than humans probably relates to the more rapid turnover and shorter life span of canine platelets. The basis for the discrepancy in return of chemical integrity compared to functional activity after aspirin in vivo compared to simultaneous correction of chemistry and function when 10% normal platelets are added to aspirin platelets in vitro remains unresolved.
在人体受试者中,口服单剂量阿司匹林后,血小板对花生四烯酸和其他试剂的聚集反应在摄入后约一周内受到抑制。在本研究中,我们评估了环氧化酶活性血小板在人和狗体内返回循环系统的速率,并将所得的反应曲线与阿司匹林处理的血小板所产生的环氧化酶活性改善情况进行了比较。单次服用阿司匹林后,狗的血小板功能受损了数天。对花生四烯酸和其他聚集剂的正常反应在服用阿司匹林六天后恢复,并且狗和人体受试者的恢复模式相同。然而,环氧化酶活性血小板在狗体内返回循环系统的速度比在人体内更快,并且在两种物种中,化学活性在对聚集剂的缺陷反应得到纠正之前就已经恢复。大量环氧化酶活性血小板返回之前1至3天的延迟很可能反映了药物对骨髓巨核细胞的乙酰化作用。狗体内化学活性细胞比人类更快返回可能与犬类血小板更快的更新率和更短的寿命有关。与体外将10%正常血小板添加到阿司匹林处理的血小板中时化学和功能同时得到纠正相比,体内服用阿司匹林后化学完整性与功能活性返回存在差异的原因仍未得到解决。