Low-frequency ultrasound induces nonenzymatic thrombolysis in vitro

Low-frequency ultrasound induces nonenzymatic thrombolysis in vitro
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DOI:
10.7863/jum.2002.21.6.649
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发表时间:
2002-06-01
影响因子:
2.3
通讯作者:
Hopf, HC
Hopf, HC
中科院分区:
医学4区
文献类型:
--
作者:
Nedelmann, M;Eicke, BM;Hopf, HC

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Objective.评估在无溶栓药物的情况下,在几厘米的距离上应用超声是否对血栓有溶栓作用。方法.本研究评价了低频(20 kHz)连续波超声在不同强度(0.15-1.2 W/cm(2))和暴露时间(5、10和20 min)下诱导新鲜人血凝块血栓溶解的可能性。还研究了超声与重组组织型纤溶酶原激活剂介导的血栓溶解的联合作用。实验在37 ℃下在脱气磷酸钠缓冲液中的流动模型中进行,从超声探头到血凝块的距离为3 cm。无论超声照射时间如何,所有实验组和对照组的血凝块均留在流动系统中20 min。与对照组相比,单独使用超声显示出显著的溶栓效果,在0.15 W/cm(2)和暴露10分钟时具有统计学显著性效果(P = 0.02),体重减轻程度与所选强度水平和暴露时间之间存在明显相关性,10个血栓中有8个在1.2 W/cm 2的功率下10分钟内完全破裂。与单独应用重组组织型纤溶酶原激活剂或超声相比,重组组织型纤溶酶原激活剂介导的溶栓中加入超声显著增强了溶栓作用(P = 0.0001),结果表明两种治疗方式的作用纯粹是相加的,无协同作用。新鲜血栓溶解效果更好。单独使用低频超声,而不添加溶栓药物,有可能在一定距离内诱导血栓溶解。超声联合重组组织型纤溶酶原激活剂上级单独治疗。超声是开发急性脑血管闭塞的替代或附加治疗方式的一种有前途的工具。
Objective. To evaluate whether ultrasound, applied over a distance of several centimeters and in the absence of thrombolytic agents, may have a thrombolytic effect on blood clots. Methods. Low-frequency (20 kHz) continuous wave ultrasound at different intensity levels (0.15-1.2 W/cm(2)) and exposure times (5, 10, and 20 minutes) was assessed for its potential to induce thrombolysis of fresh human blood clots, The ultrasound effect was also studied in combination with recombinant tissue-type plasminogen activator-mediated thrombolysis. Experiments were carried out in a flow model in degassed sodium phosphate buffer at 37degreesC at a distance of 3 cm from the ultrasonic probe to the blood clots. Regardless of ultrasound exposure times, blood clots in all experimental groups and the control group were left in the flow system for 20 minutes, Results. The use of ultrasound alone showed a significant thrombolytic effect compared with the control group, with a statistically significant effect at 0.15 W/cm(2) and exposure of 10 minutes (P = .02), There was a clear correlation between the extent of weight loss and the chosen intensity level and exposure time, Complete disruption in 8 of 10 blood clots occurred at 1.2 W/cm(2) within 10 min. Addition of ultrasound to recombinant tissue-type plasminogen activator-mediated thrombolysis significantly enhanced thrombolysis compared with application of recombinant tissue-type plasminogen activator or ultrasound alone (P = .0001), with the results pointing toward a purely additive, nonsynergistc effect of the 2 treatment modalities. Lysis was more effective in fresh thrombi, Conclusions. The use of low-frequency ultrasound alone, without addition of a thrombolytic drug, has the potential to induce thrombolysis over a distance. Combination of ultrasound with recombinant tissue-type plasminogen activator is superior to either treatment alone. Ultrasound is a promising tool for developing an alternative or additional treatment modality for acute cerebral vessel occlusion.