Nowak G, Bucha E
Max-Planck-Gesellschaft e. V., Research Unit, Pharmacological Haemostaseology, Friedrich Schiller University, Jena, Germany.
Thromb Res. 1995 Nov 15;80(4):317-25. doi: 10.1016/0049-3848(95)00182-q.
Meizothrombin, the stable intermediate product of ecarin-induced prothrombin conversion, was investigated for its ability to bind hirudin in blood. After in vitro pre-incubation of rat plasma with ecarin, the prolongation of the thrombin time caused by hirudin was reduced. The extent of hirudin neutralization was found to be dependent on the duration of incubation with ecarin. In vivo, after bilateral nephrectomy in Wistar rats and following administration of hirudin at a dose of 1 or 5 mg/kg, the blood level of hirudin remained constant after 2 h. After infusion of ecarin following hirudin administration, the hirudin blood level dropped sharply, reaching significantly reduced values, and bleeding stopped. Platelet count and fibrinogen level in plasma remained unchanged in the experiments using ecarin-induced prothrombin conversion intermediate generation. It is concluded that meizothrombin, a naturally occurring prothrombin conversion intermediate, provides an effective agent to neutralize toxic blood levels of hirudin.
对蛇毒凝血酶诱导凝血酶原转化的稳定中间产物——中凝血酶在血液中结合水蛭素的能力进行了研究。大鼠血浆与蛇毒凝血酶进行体外预孵育后，水蛭素引起的凝血酶时间延长缩短。发现水蛭素的中和程度取决于与蛇毒凝血酶的孵育时间。在体内，Wistar大鼠双侧肾切除后，以1或5mg/kg的剂量给予水蛭素，2小时后水蛭素的血药浓度保持恒定。给予水蛭素后输注蛇毒凝血酶，水蛭素血药浓度急剧下降，降至显著降低的值，出血停止。在使用蛇毒凝血酶诱导凝血酶原转化中间产物生成的实验中，血浆中的血小板计数和纤维蛋白原水平保持不变。结论是，中凝血酶作为一种天然存在的凝血酶原转化中间产物，是中和血液中毒性水平水蛭素的有效药物。
