Shishido M, Hirose R, Tanaka K, Katori M
Prostaglandins. 1982 Jun;23(6):907-17. doi: 10.1016/0090-6980(82)90133-2.
A single platelet thrombus was formed in an arteriole of the hamster cheek pouch by electrical stimulation followed by topical application of ADP. The sizes of the thrombi were continuously recorded with a photocell placed on a TV monitor screen and quantified by areas on the record. Repeated application of small doses of ADP (5-15 nmole/10 microliters) resulted in very reproducible formation of the thrombi, and the size of the thrombi was reduced dose-dependently by topical application of PGI2. Three drugs were tested in this model. Cyclooxygenase inhibitor (indomethacin 10 mg/kg, i.p.) increased the formation of thrombi, while a smaller dose (3 mg/kg) did not have any significant effect. This could be explained by inhibition of the generation of endogenous PGI2, since aggregation of hamster platelets by ADP was not inhibited by indomethacin in vitro. EG-626 (phthalazinol, a phosphodiesterase inhibitor) (300 mg/kg, i.p.) decreased the size of thrombus. AI-122 (1.0 mg/kg, i.p.), which has been proven to enhance PGI2 biosynthesis from isolated rat aortae, also decreased the formation. Thus, drugs such as EG-626 or AI-122 are quite promising as anti-thrombotic drugs.
通过电刺激并随后局部应用二磷酸腺苷（ADP），在仓鼠颊囊的小动脉中形成单个血小板血栓。血栓大小通过放置在电视监视器屏幕上的光电管连续记录，并通过记录上的面积进行量化。重复应用小剂量的ADP（5 - 15纳摩尔/10微升）导致血栓形成具有高度可重复性，并且通过局部应用前列环素（PGI2），血栓大小呈剂量依赖性减小。在该模型中测试了三种药物。环氧化酶抑制剂（吲哚美辛10毫克/千克，腹腔注射）增加了血栓形成，而较小剂量（3毫克/千克）没有任何显著影响。这可以通过抑制内源性PGI2的产生来解释，因为在体外吲哚美辛不抑制ADP诱导的仓鼠血小板聚集。EG - 626（酞嗪醇，一种磷酸二酯酶抑制剂）（300毫克/千克，腹腔注射）减小了血栓大小。已被证明能增强离体大鼠主动脉PGI2生物合成的AI - 122（1.0毫克/千克，腹腔注射）也减少了血栓形成。因此，诸如EG - 626或AI - 122之类的药物作为抗血栓药物很有前景。
