Petit B, Bohren Y, Gaud E, Bussat P, Arditi M, Yan F, Tranquart F, Allémann E
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
Bracco Suisse S.A., Plan-les-Ouates, Geneva, Switzerland.
Ultrasound Med Biol. 2015 May;41(5):1402-10. doi: 10.1016/j.ultrasmedbio.2014.12.007. Epub 2015 Jan 15.
Microbubble-mediated sonothrombolysis (STL) is a remarkable approach to vascular occlusion therapy. However, STL remains a complex process with multiple interactions between clot, ultrasound (US), microbubbles (MB) and thrombolytic drug. The aim of this study was to evaluate the ability of combining US and MB to degrade fibrin and, more specifically, to assess the roles of both stable (SC) and inertial (IC) cavitation. Human blood clots containing radiolabeled fibrin were exposed to different combinations of recombinant tissue plasminogen activator (rtPA), US (1 MHz) and phospholipid MB. Three acoustic pressures were tested: 200, 350 and 1,300 kPa (peak-negative pressure). Clot lysis was assessed by diameter loss and release of radioactive fibrin degradation products. The combination rtPA + US + MB clearly revealed that IC (1,300 kPa) was able to enhance fibrin degradation significantly (66.3 ± 1.8%) compared with rtPA alone (51.7 ± 2.0%, p < 0.001). However, SC failed to enhance fibrin degradation at an acoustic pressure of 200 kPa. At 350 kPa, a synergistic effect between rtPA and US + MB was observed with an absolute increase of 6% compared to rtPA alone (p < 0.001). Conversely, without rtPA, the combination of US + MB was unable to degrade the fibrin network (0.3 ± 0.1%, p > 0.05 vs. control), but induced a distinct loss of red blood cells throughout the entire thickness of the clot, implying that MB were able to penetrate and cavitate inside the clot.
微泡介导的超声溶栓（STL）是一种用于血管闭塞治疗的卓越方法。然而，STL仍是一个复杂的过程，涉及血凝块、超声（US）、微泡（MB）和溶栓药物之间的多种相互作用。本研究的目的是评估联合超声和微泡降解纤维蛋白的能力，更具体地说，是评估稳定空化（SC）和惯性空化（IC）的作用。将含有放射性标记纤维蛋白的人血凝块暴露于重组组织型纤溶酶原激活剂（rtPA）、超声（1兆赫）和磷脂微泡的不同组合中。测试了三种声压：200、350和1300千帕（峰值负压）。通过直径减小和放射性纤维蛋白降解产物的释放来评估血凝块溶解情况。rtPA + US + MB的组合清楚地表明，与单独使用rtPA（51.7 ± 2.0%，p < 0.001）相比，IC（1300千帕）能够显著增强纤维蛋白降解（66.3 ± 1.8%）。然而，在200千帕的声压下，SC未能增强纤维蛋白降解。在350千帕时，观察到rtPA与US + MB之间存在协同作用，与单独使用rtPA相比，绝对增加了6%（p < 0.001）。相反，在没有rtPA的情况下，US + MB的组合无法降解纤维蛋白网络（0.3 ± 0.1%，与对照组相比p > 0.05），但在血凝块的整个厚度中导致红细胞明显损失，这意味着微泡能够穿透并在血凝块内部发生空化。
