Prevention of platelet-rich arterial thrombosis by selective thrombin inhibition.
Prevention of platelet-rich arterial thrombosis by selective thrombin inhibition.
复制标题
通过选择性凝血酶抑制预防富含血小板的动脉血栓形成。
DOI：
10.1161/01.cir.81.1.219
复制
发表时间：
1990
期刊：
影响因子：
37.8
通讯作者：
Collen,D
中科院分区：
文献类型：
--
作者：
Jang,IK;Gold,HK;Ziskind,AA;Leinbach,RC;Fallon,JT;Collen,D
在兔模型中研究了肝素和合成竞争性凝血酶抑制剂（2 R，4 R）-4-甲基-1-[N2-（3-甲基-1，2，3，4-四氢-8-喹啉磺酰基）-L-乙酰基]-2-哌啶羧酸一水合物（阿加曲班）对富含血小板的动脉血栓形成的影响，该模型由4-6 mm外翻（“由内而外”）的股动脉段组成。静脉注射肝素（200单位/kg）未能在所有10只家兔中在60分钟内防止闭塞，而以100或200 μ g/kg/min的速率静脉输注阿加曲班60分钟（将凝血酶时间延长4倍以上）可在13只家兔中的9只家兔中防止血栓形成（p = 0.002 vs.静脉注射肝素）。在60分钟内动脉内输注200单位/kg肝素可防止9只家兔中的6只发生闭塞（p = 0.003 vs. i. v.肝素），而在所有10只家兔中动脉内以100 μ g/kg/min的速率输注阿加曲班60分钟可防止血栓形成（p = 0.00001 vs. i. v.肝素）。尽管凝血酶时间和部分凝血活酶时间正常化，但动脉内肝素和静脉内或动脉内阿加曲班输注结束后，股动脉节段的通畅性保持长达3小时。移植物的病理检查显示倒置的外膜表面被血小板层覆盖，没有血小板聚集或纤维蛋白沉积。这些研究结果表明，凝血酶在富含血小板的动脉血栓形成中起着重要作用，并且通过短期输注合成凝血酶抑制剂迅速减弱血栓形成刺激。选择性凝血酶抑制可作为预防不稳定冠状动脉综合征患者血管成形术或溶栓治疗后动脉闭塞的替代方法。
The effect of heparin and of the synthetic competitive thrombin inhibitor (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfon yl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate (argatroban) on platelet-rich arterial thrombosis was studied in a rabbit model, consisting of a 4-6-mm everted ("inside-out") femoral arterial segment. Intravenous injection of heparin (200 units/kg) failed to prevent occlusion within 60 minutes in all 10 rabbits, whereas intravenous argatroban infusion at a rate of 100 or 200 micrograms/kg/min for 60 minutes, which prolonged the thrombin time more than fourfold, prevented thrombosis in nine of 13 rabbits (p = 0.002 vs. i.v. heparin). Intra-arterial infusion of 200 units/kg heparin over 60 minutes prevented occlusion in six of nine rabbits (p = 0.003 vs. i.v. heparin), whereas intra-arterial argatroban at a rate of 100 micrograms/kg/min for 60 minutes prevented thrombosis in all 10 rabbits (p = 0.00001 vs. i.v. heparin). Patency of femoral arterial segments was maintained after the end of the intra-arterial heparin and intravenous or intra-arterial argatroban infusion for up to 3 hours despite normalization of the thrombin time and partial thromboplastin time. Pathologic examination of the graft revealed that the inverted adventitial surface was covered by layers of platelets without platelet aggregation or fibrin deposition. These findings indicate that thrombin plays an important role in platelet-rich arterial thrombosis, and that the thrombogenic stimulus is rapidly attenuated by short-term infusion of the synthetic thrombin inhibitor. Selective thrombin inhibition can constitute an alternative approach to the prevention of arterial occlusion after angioplasty or thrombolytic therapy in patients with unstable coronary syndromes.