Cerenovus (Johnson & Johnson), Galway Neuro Technology Centre, Galway, Ireland.
Cerenovus (Johnson & Johnson), Galway Neuro Technology Centre, Galway, Ireland; Biomedical Engineering Department, National University of Ireland Galway, Galway, Ireland.
J Biomech. 2021 Dec 2;129:110731. doi: 10.1016/j.jbiomech.2021.110731. Epub 2021 Sep 6.
Changes in acute ischemic stroke thrombi structure and composition may result in significant differences in treatment responsiveness. Ischemic stroke patients are often treated with a thrombolytic agent to dissolve thrombi, however these patients may subsequently undergo mechanical thrombectomy to remove the occlusive clot. We set out to determine if rt-PA thrombolysis treatment of blood clots changes their mechanical properties, which in turn may impact mechanical thrombectomy. Using a design-of-experiment approach, ovine clot analogues were prepared with varying composition and further exposed to different levels of compaction force to simulate the effect of arterial blood pressure. Finally, clots were treated with three r-tPA doses for different durations. Clot mass and mechanical behaviour was analysed to assess changes due to (i) Platelet driven contraction (ii) Compaction force and (iii) Thrombolysis. Clots that were exposed to r-tPA for longer duration showed significant reduction in clot mass (p < 0.001). Exposure time to r-tPA (p < 0.001) was shown to be an independent predictor of lower clot stiffness. A decrease in energy dissipation ratio during mechanical compression was associated with longer exposure time in r-tPA (p = 0.001) and a higher platelet concentration ratio (p = 0.018). The dose of r-tPA was not a significant factor in reducing clot mass or changing mechanical properties of the clots. Fibrinolysis reduces clot stiffness which may explain increased distal clot migration observed in patients treated with r-tPA and should be considered as a potential clot modification factor before mechanical thrombectomy.
急性缺血性脑卒中血栓结构和成分的变化可能导致治疗反应的显著差异。缺血性脑卒中患者通常接受溶栓药物治疗以溶解血栓，但随后可能进行机械血栓切除术以去除闭塞性血栓。我们旨在确定 rt-PA 溶栓治疗是否会改变血栓的机械性能，进而可能影响机械血栓切除术。使用实验设计方法，制备了具有不同组成的绵羊血凝块类似物，并进一步暴露于不同的压实力水平，以模拟动脉血压的影响。最后，用三种 r-tPA 剂量对血块进行不同时间的处理。分析血块的质量和机械性能，以评估由于 (i) 血小板驱动收缩、(ii) 压实力和 (iii) 溶栓而导致的变化。暴露于 r-tPA 时间较长的血栓显示出明显的血栓质量减少（p < 0.001）。r-tPA 暴露时间（p < 0.001）是降低血栓硬度的独立预测因素。在机械压缩过程中能量耗散比的降低与 r-tPA 暴露时间较长（p = 0.001）和较高的血小板浓度比（p = 0.018）相关。r-tPA 的剂量不是减少血栓质量或改变血栓机械性能的重要因素。纤维蛋白溶解降低了血栓的硬度，这可以解释在接受 r-tPA 治疗的患者中观察到的远端血栓迁移增加，在进行机械血栓切除术之前，应将其视为潜在的血栓改性因素。
