Musselman D R, Tate D A, Oberhardt B J, Abruzzini A F, Blauwet M B, Koch G, Dehmer G J
C. V. Richardson Cardiac Catheterization Laboratory, University of North Carolina Hospitals, Chapel Hill 27514.
Am J Cardiol. 1994 Mar 15;73(8):544-9. doi: 10.1016/0002-9149(94)90330-1.
This study compares the ability of 3 thrombolytic drugs to promote clot lysis using a new in vitro testing procedure. Whole blood samples from 132 patients were tested using 5 different concentrations of tissue-type plasminogen activator (t-PA), streptokinase (SK) and urokinase. A mixture of blood and thrombolytic drug was placed on a dry-reagent test card containing reptilase, buffers and paramagnetic particles where clot formation occurred. Analysis of the motion of the clot-embedded paramagnetic particles caused by an oscillating magnetic field was used to define the lysis onset time. The slope of the linear regression plot of lysis onset time versus 1/[drug concentration] defined the kinetic rate constant (k) for each drug in each patient. Higher values of k indicated greater resistance to in vitro clot lysis. In the patients studied, there was a large range of k values for t-PA and SK (coefficient of variation 143 and 137%, respectively) but a smaller range of k for urokinase (coefficient of variation 32%). The coefficients of variation for t-PA and SK observed in the study group were five- to 10-fold greater than the coefficients of variation determined for replicate test measurements. Resistance to all SK concentrations tested was found in 9% of the patients. In vitro sensitivity to thrombolysis was compared among the drugs by correlating the derived k values. These comparisons indicated no relation for any of the drugs; many patients had a relatively low k value for 1 drug, while having a relatively high k value for a different drug.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究采用一种新的体外测试程序,比较了3种溶栓药物促进血栓溶解的能力。使用5种不同浓度的组织型纤溶酶原激活剂(t-PA)、链激酶(SK)和尿激酶,对132例患者的全血样本进行了测试。将血液与溶栓药物的混合物置于含有蛇毒凝血酶、缓冲液和顺磁性颗粒的干试剂测试卡上,在此处形成凝块。通过分析振荡磁场引起的包埋在凝块中的顺磁性颗粒的运动来确定溶解开始时间。溶解开始时间与1/[药物浓度]的线性回归图的斜率定义了每位患者每种药物的动力学速率常数(k)。k值越高,表明对体外血栓溶解的抵抗力越强。在所研究的患者中,t-PA和SK的k值范围很大(变异系数分别为143%和137%),而尿激酶的k值范围较小(变异系数为32%)。研究组中观察到的t-PA和SK的变异系数比重复测试测量确定的变异系数大5至10倍。9%的患者对所有测试浓度的SK均有抵抗。通过关联得出的k值,比较了各药物之间的体外溶栓敏感性。这些比较表明,任何一种药物之间均无关联;许多患者对一种药物的k值相对较低,而对另一种药物的k值相对较高。(摘要截短于250字)