Stone Michael J, Frenkel Victor, Dromi Sergio, Thomas Peter, Lewis Ryan P, Li King C P, Horne McDonald, Wood Bradford J
Diagnostic Radiology Department, Clinical Center, National Institutes of Health, Building 10, Room 1N306a, 10 Center Drive, Bethesda, MD 20892, USA.
Thromb Res. 2007;121(2):193-202. doi: 10.1016/j.thromres.2007.03.023. Epub 2007 May 4.
Thrombotic disease continues to account for significant morbidity and mortality. Ultrasound energy has been investigated as a potential primary and adjunctive treatment for thrombotic disease. We have previously shown that pulsed-high intensity focused ultrasound (HIFU) enhances thrombolysis induced by tissue plasminogen activator (tPA) in vitro, including describing the non-destructive mechanism by which tPA availability and consequent activity are increased. In this study we aimed to determine if the same effects could be achieved in vivo.
In this study, pulsed-HIFU exposures combined with tPA boluses were compared to treatment with tPA alone, HIFU alone and control in a novel in vivo clot model. Clots were formed in the rabbit marginal ear vein and verified using venography and infrared imaging. The efficacy of thrombolytic treatment was monitored via high resolution ultrasonography for 5 h post-treatment. The cross-sectional area of clots at 4 points along the vein was measured and normalized to the pre-treatment size.
At 5 h the complete recanalization of clots treated with pulsed-HIFU and tPA was significantly different from the partial recanalization seen with tPA treatment alone. tPA treatment alone showed a significant decrease in clot versus control, where HIFU was not significantly different than control. Histological analysis of the vessel walls in the treated veins showed no apparent irreversible damage to endothelial cells or extravascular tissue.
This study demonstrates that tPA mediated thrombolysis can be significantly enhanced when combined with non-invasive pulsed-HIFU exposures.
血栓性疾病仍然是导致显著发病率和死亡率的原因。超声能量已被研究作为血栓性疾病的一种潜在的主要和辅助治疗方法。我们之前已经表明，脉冲高强度聚焦超声（HIFU）在体外可增强组织型纤溶酶原激活剂（tPA）诱导的溶栓作用，包括描述tPA可用性及后续活性增加的非破坏性机制。在本研究中，我们旨在确定在体内是否能取得相同的效果。
在本研究中，在一种新型体内血栓模型中，将脉冲HIFU照射联合tPA推注与单独使用tPA治疗、单独使用HIFU治疗及对照进行比较。在兔耳缘静脉形成血栓，并通过静脉造影和红外成像进行验证。溶栓治疗的疗效在治疗后5小时通过高分辨率超声进行监测。测量静脉沿线4个点处血栓的横截面积，并将其归一化为治疗前大小。
在5小时时，脉冲HIFU和tPA联合治疗的血栓完全再通与单独tPA治疗所见的部分再通有显著差异。单独tPA治疗与对照相比血栓有显著减少，而HIFU与对照无显著差异。对治疗静脉的血管壁进行组织学分析显示，内皮细胞或血管外组织没有明显的不可逆损伤。
本研究表明，tPA介导的溶栓与非侵入性脉冲HIFU照射联合时可显著增强。
