Korbut R, Gryglewski R J
Department of Pharmacology, Medical College of Jagiellonian University, Cracow, Poland.
Methods Find Exp Clin Pharmacol. 1996 Apr;18(3):167-74.
Here we report that streptokinase is responsible for forming thrombi both in vitro on blood-superfused endothelial cells of rabbit aorta and in vivo on blood-superfused collagen strips in extracorporal circulation of anesthetized cats. This short-lasting paradoxical thrombogenic phase is followed by the expected long-lasting thrombolysis. The biphasic action of streptokinase occurred in vitro at concentrations of 100-2000 U/ml and in vivo at doses of 1000-3000 U/kg i.v. Both phases are mediated by endogenous plasmin as evidenced by deleting the streptokinase-induced thrombogenesis and thrombolysis following pretreatment with epsilon-aminocaproic acid or aprotinin. On the other hand, selective block of the paradoxical thrombogenesis was achieved after pretreatment with camonagrel, a thromboxane synthase inhibitor which raises plasma levels of endogenous prostacyclin, or with iloprost, a stable analog of prostacyclin. It is suggested that endogenous or exogenous prostacyclin inhibits activation of platelets by plasmin, and hence the thrombogenesis by streptokinase is abolished, while the beneficial thrombolytic action of streptokinase is augmented.
我们在此报告，链激酶在体外对兔主动脉血液灌注的内皮细胞以及在体内对麻醉猫体外循环中的血液灌注胶原条均有形成血栓的作用。这种短暂的矛盾性血栓形成期之后是预期的持久溶栓期。链激酶的双相作用在体外浓度为100 - 2000 U/ml时出现，在体内静脉注射剂量为1000 - 3000 U/kg时出现。两个阶段均由内源性纤溶酶介导，用ε-氨基己酸或抑肽酶预处理后，链激酶诱导的血栓形成和溶栓作用消失即证明了这一点。另一方面，用卡莫格雷（一种提高内源性前列环素血浆水平的血栓素合酶抑制剂）或伊洛前列素（前列环素的稳定类似物）预处理后，可实现对矛盾性血栓形成的选择性阻断。提示内源性或外源性前列环素抑制纤溶酶对血小板的激活，因此链激酶的血栓形成作用被消除，而链激酶有益的溶栓作用则增强。
