Division of Cardiovascular Diseases and Biomedical Engineering Program, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
Ultrasound Med Biol. 2011 Aug;37(8):1240-51. doi: 10.1016/j.ultrasmedbio.2011.05.011.
Ultrasound is known to enhance recombinant tissue plasminogen activator (rt-PA) thrombolysis. In this study, occlusive porcine whole blood clots were placed in flowing plasma within living porcine carotid arteries. Ultrasonically induced stable cavitation was investigated as an adjuvant to rt-PA thrombolysis. Aged, retracted clots were exposed to plasma alone, plasma containing rt-PA (7.1 ± 3.8 μg/mL) or plasma with rt-PA and Definity® ultrasound contrast agent (0.79 ± 0.47 μL/mL) with and without 120-kHz continuous wave ultrasound at a peak-to-peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity®-rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt-PA and Definity® without ultrasound (n = 7) was 34%, and with ultrasound (n = 6) was 83%, which constituted a significant difference (p < 0.0001). Without Definity® there was no thrombolytic enhancement by ultrasound exposure alone at this pressure amplitude (n = 5, p < 0.0001). In the low-oxygen environment of the ischemic artery, significant loss of endothelium occurred but no correlation was observed between arterial tissue damage and treatment type. Acoustic stable cavitation nucleated by an infusion of Definity® enhances rt-PA thrombolysis without apparent treatment-related damage in this ex vivo porcine carotid artery model.
超声已知可增强重组组织纤溶酶原激活物（rt-PA）溶栓。在这项研究中，将闭塞的猪全血凝块放置在活体猪颈动脉内的流动血浆中。研究了作为 rt-PA 溶栓辅助剂的超声诱导稳定空化。将陈旧的回缩凝块暴露于单独的血浆、含有 rt-PA（7.1 ± 3.8 μg/mL）的血浆或含有 rt-PA 和 Definity®超声造影剂（0.79 ± 0.47 μL/mL）的血浆中，同时和不使用 120-kHz 连续波超声，峰值-峰值压力幅度为 0.44 MPa。制定了一种照射方案，通过结合允许富含 Definity®的血浆流入的超声静止期来促进和最大化稳定空化活性。在整个溶栓治疗过程中，用被动声学探测器测量空化。通过比较治疗前后的凝块质量来测量溶栓效果。未暴露于超声的 rt-PA 和 Definity®（n = 7）凝块的平均质量损失为 34%，而暴露于超声的凝块（n = 6）的质量损失为 83%，这构成了显著差异（p < 0.0001）。在这种压力幅度下，没有 Definity®的情况下，单独超声暴露没有溶栓增强作用（n = 5，p < 0.0001）。在缺血动脉的低氧环境中，内皮细胞大量丢失，但动脉组织损伤与治疗类型之间没有观察到相关性。通过输注 Definity®引发的声空化核增强了 rt-PA 溶栓，在这种体外猪颈动脉模型中没有明显的治疗相关损伤。
