Harpaz D, Chen X, Francis C W, Marder V J, Meltzer R S
Cardiology Unit, University of Rochester, New York 14642-8679.
J Am Coll Cardiol. 1993 May;21(6):1507-11. doi: 10.1016/0735-1097(93)90331-t.
The aims of this study were 1) to develop an in vitro flow system in which reperfusion mediated by ultrasound-accelerated thrombolysis could be studied, and 2) to test whether ultrasound-accelerated thrombolysis could hasten reperfusion in this system.
Ultrasound has been shown to increase tissue plasminogen activator (t-PA)-induced thrombolysis in vitro as assessed by radioactive fibrinogen release from labeled clots and in an animal in vivo model.
To test whether reperfusion is accelerated, we created obstructive whole blood clots in an in vitro flow system. Four control clots were exposed to ultrasound only without any thrombolytic agent (group 1). Sixteen clots were exposed to continuous infusion of recombinant tissue-type plasminogen activator rt-PA and randomized to either continuous wave ultrasound exposure at a frequency of 0.5 MHz and an intensity of 8 W/cm2 (group 2) or to no ultrasound (group 3). Flow distal to the clot and the rate of release of radiolabeled fibrin products were used as an index of reperfusion and thrombolysis, respectively. Samples were obtained for measurements of lytic variables such as plasminogen, fibrinogen and rt-PA concentrations.
Flow was significantly higher in the rt-PA-treated clots within 10 min of exposure to ultrasound than in those without such exposure (9.4 +/- 9.9% of maximal flow in group 2 vs. 0.5 +/- 1.5% in group 3, p < 0.05). The maximal difference in flow between groups 2 and 3 was achieved at 25 min (61.0 +/- 30.4% vs. 14.2 +/- 14.7%, p = 0.03). Thrombolysis was significantly higher after 15 min of ultrasound exposure (12.8 +/- 9.1% in the ultrasound-treated group 2 vs. 4.0 +/- 3.9% in group 3, p < 0.05). The maximal difference between groups 2 and 3 occurred at 25 min (26.7 +/- 13.1% vs. 7.24 +/- 5.7%, p < 0.004). Neither flow nor clot lysis occurred in group 1. Plasminogen and fibrinogen concentrations and rt-PA antigen concentrations were consistent with those observed during fibrinolytic therapy in vivo.
Continuous wave ultrasound at 0.5 MHz and an intensity of 8 W/cm2 accelerates rt-PA-induced thrombolysis and reperfusion in vitro.
本研究的目的是：1）开发一种体外流动系统，用于研究超声加速溶栓介导的再灌注；2）测试超声加速溶栓是否能在该系统中加速再灌注。
在体外，通过标记血凝块中放射性纤维蛋白原的释放评估，以及在动物体内模型中，超声已被证明可增强组织纤溶酶原激活物（t-PA）诱导的溶栓作用。
为测试再灌注是否加速，我们在体外流动系统中制造阻塞性全血凝块。4个对照血凝块仅接受超声照射，不使用任何溶栓剂（第1组）。16个血凝块接受重组组织型纤溶酶原激活物rt-PA的持续输注，并随机分为两组，一组接受频率为0.5 MHz、强度为8 W/cm2的连续波超声照射（第2组），另一组不接受超声照射（第3组）。血凝块远端的血流以及放射性标记纤维蛋白产物的释放速率分别用作再灌注和溶栓的指标。采集样本测量纤溶变量，如纤溶酶原、纤维蛋白原和rt-PA浓度。
在接受超声照射10分钟内，rt-PA处理的血凝块中的血流显著高于未接受超声照射的血凝块（第2组为最大血流的9.4±9.9%，第3组为0.5±1.5%，p<0.05）。第2组和第3组之间血流的最大差异在25分钟时达到（61.0±30.4%对14.2±14.7%，p = 0.03）。超声照射15分钟后溶栓作用显著增强（超声处理的第2组为12.8±9.1%，第3组为4.0±3.9%，p<0.05）。第2组和第3组之间的最大差异出现在25分钟时（26.7±13.1%对7.24±5.7%，p<0.004）。第1组既未出现血流增加也未出现血凝块溶解。纤溶酶原、纤维蛋白原浓度以及rt-PA抗原浓度与体内纤溶治疗期间观察到的一致。
频率为0.5 MHz、强度为8 W/cm2的连续波超声可在体外加速rt-PA诱导的溶栓和再灌注。
