Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model
Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model
复制标题
DOI：
10.1016/j.thromres.2007.07.006
复制
发表时间：
2008-01-01
影响因子：
7.5
通讯作者：
Shaw, George J.
中科院分区：
文献类型：
--
作者：
Holland, Christy K.;Vaidya, Sampada S.;Shaw, George J.
简介：重组组织型纤溶酶原激活剂（recombinant tissue plasminogen activator，rt-PA）等溶栓药物在治疗缺血性脑卒中、心肌梗死、深静脉血栓形成和肺栓塞等方面取得了显著进展，目的：探讨rt-PA与120 kHz或1.0MHz超声的协同溶栓作用。材料与方法：采用新鲜猪血液制备的完全收缩的全血凝块，比较暴露于120 kHz或1 MHz超声和不暴露于120 kHz或1 MHz超声的rt-PA溶栓治疗。对于假手术研究（无超声），测量凝块质量损失与rt-PA浓度（0.003 - 0.107 mg/ml）的函数关系。对于联合超声和rt-PA治疗，采用0.35、0.70或1.0 MPa的峰-峰压力振幅。占空比范围为10%~ 100%（连续波），脉冲重复频率固定为1.7KHz.Results：对于rt-PA，质量损失随rt-PA浓度的增加而单调增加，直至约0.050mg/ml。超声和rt-PA暴露，凝块质量损失增加多达104%，超过rt-PA补偿。与对照治疗相比，不存在rt-PA的超声没有显著增强溶栓作用。超声介导的凝块质量损失增强增加的平方根的整体treatmentduty.Conclusions：120 kHz和1 MHz脉冲和CW超声增强的rt-PA溶栓在猪全血凝块模型在体外。观察到的溶栓增强对超声占空比的依赖性不明显。占空比依赖性的缺乏表明了一种更复杂的机制，其不能仅通过增加脉冲持续时间来维持。(C)2007爱思唯尔有限公司保留所有权利。
Introduction: Thrombolytics such as recombinant tissue plasminogen activator (rt-PA) have advanced the treatment of ischemic stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism.Objective: To improve the efficacy of this thrombolytic therapy, the synergistic effect of rt-PA and 120 kHz or 1.0MHz ultrasound was assessed in vitro using a porcine clot model. Materials and methods: Fully retracted whole blood clots prepared from fresh porcine blood were employed to compare rt-PA thrombolytic treatment with and without exposure to 120-kHz or 1 -MHz ultrasound. For sham studies (without ultrasound), clot mass loss was measured as a function of rt-PA concentration from 0.003 to 0.107 mg/ml. For combined ultrasound and rt-PA treatments, peak-to-peak pressure amplitudes of 0.35, 0.70 or 1.0 MPa were employed. The range of duty cycles varied from 10% to 100% (continuous wave) and the pulse repetition frequency was fixed at 1.7 KHz.Results: For rt-PA atone, the mass toss increased monotonically as a function of rt-PA concentration up to approximately 0.050 mg/ml. With ultrasound and rt-PA exposure, clot mass loss increased by as much as 104% over rt-PA atone. Ultrasound without the presence of rt-PA did not significantly enhance thrombolysis compared to control treatment. The ultrasound -mediated clot mass loss enhancement increased with the square root of the overall treatment duration.Conclusions: Both 120-kHz and 1 -MHz pulsed and CW ultrasound enhanced rt-PA thrombolysis in a porcine whole blood clot model in vitro. No clear dependence of the observed thrombolytic enhancement on ultrasound duty cycle was evident. The lack of duty cycle dependence suggests a more complex mechanism that could not be sustained by merely increasing the pulse duration. (C) 2007 Elsevier Ltd. All rights reserved.