Fitzgerald D J, Catella F, Roy L, FitzGerald G A
Divisions of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232.
Circulation. 1988 Jan;77(1):142-50. doi: 10.1161/01.cir.77.1.142.
We assessed thromboxane biosynthesis as an index of platelet activation in 6 patients with acute myocardial infarction receiving intravenous streptokinase. Urinary 2,3-dinor-thromboxane B2 and plasma 11-dehydro-thromboxane B2, major enzymatic metabolites of thromboxane A2, were markedly increased after intravenous streptokinase (11,063 +/- 2758 pg/mg creatinine and 33 +/- 10 pg/ml, respectively) compared with levels in patients not receiving thrombolytic therapy (502 +/- 89 pg/mg creatinine and 3 +/- 0.7 pg/ml). Prostacyclin biosynthesis also increased markedly after streptokinase coincident with the increase in thromboxane A2 formation. Administration of aspirin between the time of onset of coronary thrombosis and reperfusion both in man and in a canine preparation demonstrated that this reflected thromboxane biosynthesis de novo and not metabolism of preformed inactive thromboxane B2 washed out from the coronary circulation. Since the platelet is the major source of thromboxane A2, these findings suggest that there is marked platelet activation after coronary thrombolysis with streptokinase. Studies in vitro demonstrated that streptokinase enhanced platelet activation in a dose-dependent manner, resulting in the secondary release of thromboxane A2. The increase in platelet activation and thromboxane A2 biosynthesis may limit the therapeutic effect of intravenous streptokinase in acute myocardial infarction.
我们评估了6例接受静脉链激酶治疗的急性心肌梗死患者的血栓素生物合成，以此作为血小板活化的指标。与未接受溶栓治疗的患者相比，静脉注射链激酶后，血栓素A2的主要酶促代谢产物尿2,3-二去甲血栓素B2和血浆11-脱氢血栓素B2显著增加（分别为11,063±2758 pg/mg肌酐和33±10 pg/ml）（未接受溶栓治疗患者的水平分别为502±89 pg/mg肌酐和3±0.7 pg/ml）。链激酶治疗后，前列环素生物合成也显著增加，与血栓素A2生成的增加同时出现。在人和犬类制剂中，在冠状动脉血栓形成至再灌注期间给予阿司匹林表明，这反映了血栓素的从头生物合成，而非从冠状动脉循环中清除的预先形成的无活性血栓素B2的代谢。由于血小板是血栓素A2的主要来源，这些发现表明，链激酶冠状动脉溶栓后存在明显的血小板活化。体外研究表明，链激酶以剂量依赖的方式增强血小板活化，导致血栓素A2的二次释放。血小板活化和血栓素A2生物合成的增加可能会限制静脉链激酶在急性心肌梗死中的治疗效果。
