Papadopoulos Nicos, Damianou Christakis
Department of Bioengineering, City University, London, UK.
Electrical Engineering Department, Cyprus University of Technology, Limassol, Cyprus.
J Stroke Cerebrovasc Dis. 2017 Jun;26(6):1287-1296. doi: 10.1016/j.jstrokecerebrovasdis.2017.01.023. Epub 2017 Feb 22.
The aim of the proposed study was to evaluate in an in vitro flow model the ability of small planar rectangular (2 × 10 mm) ultrasonic transducer to enhance thrombolysis induced by the thrombolytic agent tenecteplase (TNK-tPA).
To provide a more realistic clinical environment of stroke, the study was conducted under realistic flow conditions and TNK-tPA concentrations. Fully retracted porcine blood clots were used to determine the thrombolytic efficacy of ultrasound (US) waves as an adjunct to TNK-tPA or in combination with microbubbles (MBs). Two ultrasonic flat rectangular transducers were used in the experiments, operating at 3.7 and 5.2 MHz respectively. A pulsed US protocol that maintained temperature elevation at the target of 1°C was applied. Thrombolysis efficacy was measured in milligrams of mass clot removed.
The effect of experimental parameters, such as power, frequency, and MBs administration, on thrombolysis efficacy was explored.
The results revealed that thrombolysis efficacy decreases at higher frequency, and therefore, the possibility of using lower frequency to improve efficacy should be further investigated. Additionally, study findings demonstrated that the combination of 3.7 MHz with MBs as an adjunct to TNK-tPA strongly enhanced thrombolysis efficacy, because with 30 minutes of treatment, 700 mg of clot was removed through nonthermal mechanisms. As a final point, this study has shown that MBs dose influences thrombolysis enhancement, because higher thrombolytic efficacy was observed with higher doses of MBs.
本拟开展研究的目的是在体外血流模型中评估小型平面矩形（2×10毫米）超声换能器增强溶栓剂替奈普酶（TNK-tPA）诱导溶栓的能力。
为提供更贴近临床实际的中风环境，本研究在实际血流条件和TNK-tPA浓度下进行。使用完全回缩的猪血凝块来确定超声波（US）作为TNK-tPA辅助手段或与微泡（MBs）联合使用时的溶栓效果。实验中使用了两个超声扁平矩形换能器，分别工作在3.7和5.2兆赫兹。采用了将目标温度升高维持在1°C的脉冲超声方案。溶栓效果以去除的血凝块质量（毫克）来衡量。
探讨了功率、频率和微泡给药等实验参数对溶栓效果的影响。
结果显示，在较高频率下溶栓效果会降低，因此，应进一步研究使用较低频率来提高疗效的可能性。此外，研究结果表明，3.7兆赫兹与微泡联合作为TNK-tPA的辅助手段可显著增强溶栓效果，因为经过30分钟的治疗，通过非热机制去除了700毫克血凝块。最后，本研究表明微泡剂量会影响溶栓增强效果，因为较高剂量的微泡观察到了更高的溶栓效果。
