University of Cincinnati, Biomedical Engineering Program, College of Engineering and Applied Science, Cincinnati, OH 45267, USA.
Ultrasound Med Biol. 2013 May;39(5):813-24. doi: 10.1016/j.ultrasmedbio.2012.12.008. Epub 2013 Mar 1.
We investigated ultrasound-enhanced thrombolysis in two whole-blood clot models using a Food and Drug Administration-approved contrast agent (Definity, Lantheus Medical Imaging; Billerica, MA USA) and thrombolytic drug (recombinant tissue-type plasminogen activator [rt-PA]) (Genentech; South San Francisco, CA USA). Porcine venous blood was collected from donor hogs and coagulated in vials made of two different materials. This method produced clots with differing compositional properties, as determined by routine scanning electron microscopy and histology. Clots were deployed in an ex vivo porcine thrombosis model, and exposed to an intermittent ultrasound scheme previously developed to maximize stable cavitation while acoustic emissions were detected. Exposure to 3.15 μg/mL rt-PA promoted lysis in both clot models, compared with exposure to plasma alone. However, only unretracted clots experienced significant enhancement of thrombolysis in the presence of rt-PA, Definity, and ultrasound, compared with treatment with rt-PA. In these clots, microscopy revealed loose erythrocyte aggregates, a significantly less extensive fibrin network and a higher porosity, which may facilitate increased penetration of thrombolytics by cavitation.
我们使用美国食品和药物管理局批准的造影剂（Definity，Lantheus Medical Imaging；比勒陀利亚，马萨诸塞州美国）和溶栓药物（重组组织型纤溶酶原激活剂[rt-PA]）（基因泰克；加利福尼亚州旧金山）在两种全血凝块模型中研究了超声增强溶栓。从供体猪中采集猪静脉血，并在由两种不同材料制成的小瓶中凝固。通过常规扫描电子显微镜和组织学确定，这种方法产生了具有不同组成特性的凝块。将凝块部署在体外猪血栓形成模型中，并暴露于先前开发的间歇式超声方案中，以在检测到声发射的同时最大限度地提高稳定空化。与单独暴露于血浆相比，在两种凝块模型中，3.15μg/ml 的 rt-PA 促进了溶解。然而，只有未缩回的凝块在 rt-PA、Definity 和超声存在的情况下经历了溶栓的显著增强，与 rt-PA 治疗相比。在这些凝块中，显微镜显示出松散的红细胞聚集物，纤维蛋白网络的范围明显较小，孔隙率较高，这可能有利于空化作用增加溶栓药物的渗透。
