Potentiating intra-arterial sonothrombolysis for acute ischemic stroke by the addition of the ultrasound contrast agents (Optison™ & SonoVue(®)).

Potentiating intra-arterial sonothrombolysis for acute ischemic stroke by the addition of the ultrasound contrast agents (Optison™ & SonoVue(®)).
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DOI:
10.1007/s11239-010-0483-3
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发表时间:
2011-01
影响因子:
4
通讯作者:
Hansmann DR
Hansmann DR
中科院分区:
医学4区
文献类型:
--
作者:
Soltani A;Singhal R;Obtera M;Roy RA;Clark WM;Hansmann DR

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经颅超声联合静脉注射超声造影剂(UCA)在存在或不存在重组组织纤溶酶原激活剂(rt-PA)的情况下已被广泛评价为治疗缺血性卒中的新模式。尽管成功证明了加速凝块溶解,但存在与该模式相关的固有局限性,例如时间窗厚度不一致和/或对静脉注射UCA的潜在严重心肺反应,这阻碍了其在缺血性卒中人群中的广泛应用。作为一种补充方式,我们评估了通过动脉内超声同时在凝块内输送UCA和rt-PA的潜在溶解增强作用。为此,通过调节凝血酶浓度,形成具有与临床上收缩的凝块相似的平均孔径的凝块。使用显微镜方法测定通过导管递送后UCA的物理特性和保留作为临床相关流速6、12、18 ml/h的函数。本研究中使用的UCA(Optison和SonoVue)穿透凝块的能力通过超声B型成像进行验证。在存在和不存在稀释至1:10、1:100和1:200 v/v的UCA的情况下,在1.3和2.1 MPa的两个峰值稀疏声压下,使用称重法评价凝块溶解作为rt-PA浓度(0.009至0.5 mg/ml)的函数。研究结果表明,仅向0.009、0.05、0.3和0.5 mg/ml的rt-PA中加入0.02 ml 1:100稀释的UCA,在峰值稀疏声压为1.3 MPa的情况下,裂解率分别提高3.9、2.6、1.9和1.8倍,在峰值稀疏声压为2.1 MPa的情况下,裂解率分别提高5.1、3.4、2.6和3.1倍。此外,Optison和SonoVue在提高血凝块溶解率方面表现出相当的有效性。在动脉内超声溶栓的基础上增加UCA可以被认为是缺血性卒中患者的一种可行的治疗选择。
Transcranial ultrasound in combination with intravenously administered ultrasound contrast agents (UCA) in the presence or absence of recombinant tissue plasminogen activator (rt-PA) has been widely evaluated as a new modality for treatment of ischemic stroke. Despite the successful demonstration of accelerated clot lysis there are inherent limitations associated with this modality such as inconsistency in temporal window thickness and/or potential serious cardiopulmonary reactions to intravenous administration of UCA that prevent broad application to ischemic stroke populations. As a complementary modality, we evaluated potential lysis enhancement by intraarterial ultrasound with concurrent intra-clot delivery of UCA and rt-PA. To this end, clots were formed with average pore diameter similar to clinically retracted clots by adjusting the thrombin concentration. Physical characteristic and retention of UCA after delivery through the catheter as a function of clinically relevant flow rates of 6, 12, 18 ml/h were determined using a microscopic method. The ability of the UCA employed in this study, Optison and SonoVue, to penetrate into the clot was verified using ultrasound B-mode imaging. Clot lysis as a function of rt-PA concentration, 0.009 through 0.5 mg/ml, in the presence and absence of UCA diluted to 1:10, 1:100, and 1:200 v/v at two Peak rarefaction acoustic pressures of 1.3 and 2.1 MPa were evaluated using a weighing method. The study results suggest the addition of only 0.02 ml of 1:100 diluted UCA to rt-PA of 0.009, 0.05, 0.3, and 0.5 mg/ml can enhance the lysis rate by 3.9, 2.6, 1.9 and 1.8 fold in the presence of peak rarefaction acoustic pressure of 1.3 MPa and by 5.1, 3.4, 2.6, 3.1 in the presence of peak rarefaction acoustic pressure of 2.1 MPa, respectively. In addition, Optison and SonoVue demonstrated comparable effectiveness in enhancing the clot lysis rate. Addition of UCA to intra-arterial sonothrombolysis could be considered as a viable treatment option for ischemic stroke patients.
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DOI: 10.1161/strokeaha.109.192535
发表时间: 2009-08
期刊: Stroke
影响因子: 8.3
作者:
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