PREVENTION OF ARTERIAL REOCCLUSION AFTER THROMBOLYSIS WITH RECOMBINANT LIPOPROTEIN ASSOCIATED COAGULATION INHIBITOR
PREVENTION OF ARTERIAL REOCCLUSION AFTER THROMBOLYSIS WITH RECOMBINANT LIPOPROTEIN ASSOCIATED COAGULATION INHIBITOR
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DOI：
10.1161/01.cir.84.2.821
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发表时间：
1991-08-01
期刊：
影响因子：
37.8
通讯作者：
ABENDSCHEIN, DR
中科院分区：
文献类型：
--
作者：
HASKEL, EJ;TORR, SR;ABENDSCHEIN, DR
背景 本研究的目的是确定是否动脉再闭塞溶栓后可以防止脂蛋白相关凝血抑制剂（LACI），组织因子诱导的凝血介导的外在pathway.Methods和结果的生理抑制剂。 在麻醉犬的股动脉中诱导血栓形成，使用阳极电流引起广泛的血管损伤并在一条动脉中形成富含血小板的血栓，使用血栓形成铜线引起富含纤维蛋白的血栓，而对侧动脉中没有明显的血管损伤。 用t-PA（1.7 mg/kg，静脉注射1小时）诱导两条血管再通，并用多普勒血流探头进行验证。 在没有LACI的情况下，电损伤诱导血栓形成的7条动脉中有7条在2小时内发生再闭塞，铜线诱导血栓形成的7条动脉中有4条在2小时内发生再闭塞。 在给狗输注重组DNA产生的LACI（225 μ g/kg，15分钟内，随后4 μ g/kg/min i. v.）在完成t-PA的输注后，在2小时的观察间隔期间，在经受电损伤的五条动脉中的任何一条中均未发生再闭塞（p < 0.001），并且周期性部分闭塞几乎消失（LACI处理的狗中为0.4 ± 0.4/hr，而盐水处理的狗中为13.7 ± 5.5/hr，p < 0.0001）。 与此相反，再闭塞发生在两个留置铜线的五个动脉，和周期性部分闭塞不受影响，尽管LACI。 LACI适度延长部分凝血活酶时间（1.7 +/- 0.2 x基线），但不影响体外评估的血小板计数或聚集。 用LACI抑制外源性凝血途径可预防广泛血管损伤血管溶栓后血栓性动脉再闭塞。 我们的研究结果表明，外源性通路的激活在血栓性再闭塞中起着关键作用，LACI提供了一种高度靶向的方法，以促进持续再通，而不直接抑制血小板。
Background. This study was designed to determine whether arterial reocclusion after thrombolysis can be prevented by lipoprotein-associated coagulation inhibitor (LACI), a physiological inhibitor of tissue factor-induced coagulation mediated by the extrinsic pathway.Methods and Results. Thrombosis was induced in femoral arteries of anesthetized dogs with the use of anodal current to elicit extensive vascular injury and formation of platelet-rich thrombi in one artery and with thrombogenic copper wire to elicit fibrin-rich thrombi without appreciable vascular injury in the contralateral artery. Recanalization of both vessels was induced with t-PA (1.7 mg/kg i.v. over 1 hour) and verified with Doppler flow probes. Reocclusion occurred within 2 hours in seven of seven arteries with electrical injury-induced thrombosis and in four of seven arteries with copper wire-induced thrombosis in the absence of LACI. In dogs given infusions of recombinant DNA-produced LACI (225-mu-g/kg over 15 minutes, followed by 4-mu-g/kg/min i.v.) after completion of the infusion of t-PA, no reocclusion occurred during the 2-hour interval of observation in any of the five arteries subjected to electrical injury (p < 0.001), and cyclic partial occlusions were nearly abolished (0.4 +/- 0.4/hr in LACI-treated dogs compared with 13.7 +/- 5.5/hr in saline-treated dogs, p < 0.0001). In contrast, reocclusion occurred in two of five arteries with indwelling copper wires, and cyclic partial occlusions were unaffected despite LACI. LACI prolonged the partial thromboplastin time modestly (1.7 +/- 0.2 x baseline) but did not affect platelet counts or aggregation assessed ex vivo.Conclusions. Inhibition of the extrinsic pathway of coagulation with LACI prevents thrombotic arterial reocclusion after thrombolysis in vessels subjected to extensive vascular injury. Our results demonstrate that activation of the extrinsic pathway plays a critical role in thrombotic reocclusion and that LACI provides a highly targeted approach to facilitate sustained recanalization without directly inhibiting platelets.