Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, USA.
Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
Ultrasound Med Biol. 2024 Aug;50(8):1167-1177. doi: 10.1016/j.ultrasmedbio.2024.04.002. Epub 2024 May 22.
Standard treatment for deep vein thrombosis (DVT) involves catheter-directed anticoagulants or thrombolytics, but the chronic thrombi present in many DVT cases are often resistant to this therapy. Histotripsy has been found to be a promising adjuvant treatment, using the mechanical action of cavitating bubble clouds to enhance thrombolytic activity. The objective of this study was to determine if histotripsy enhanced recombinant tissue plasminogen activator (rt-PA) thrombolysis in highly retracted porcine clots in vitro in a flow model of occlusive DVT.
Highly retracted porcine whole blood clots were treated for 1 h with either catheter-directed saline (negative control), rt-PA (lytic control), histotripsy, DEFINITY and histotripsy or the combination of rt-PA and histotripsy with or without DEFINITY. Five-cycle, 1.5 MHz histotripsy pulses with a peak negative pressure of 33.2 MPa and pulse repetition frequency of 40 Hz were applied along the clot. B-Mode and passive cavitation images were acquired during histotripsy insonation to monitor bubble activity.
Clots subjected to histotripsy with and without rt-PA exhibited greater thrombolytic efficacy than controls (7.0% flow recovery or lower), and histotripsy with rt-PA was more efficacious than histotripsy with saline (86.1 ± 10.2% compared with 61.7 ± 19.8% flow recovery). The addition of DEFINITY to histotripsy with or without rt-PA did not enhance either thrombolytic efficacy or cavitation dose. Cavitation dose generally did not correlate with thrombolytic efficacy.
Enhancement of thrombolytic efficacy was achieved using histotripsy, with and without catheter-directed rt-PA, in the presence of physiologic flow. This suggests these treatments may be effective as therapy for DVT.
深静脉血栓形成（DVT）的标准治疗包括导管定向抗凝剂或溶栓剂，但许多 DVT 病例中存在的慢性血栓通常对这种治疗有抵抗力。组织爆破已被发现是一种很有前途的辅助治疗方法，它利用空化气泡云的机械作用来增强溶栓活性。本研究的目的是确定在闭塞性 DVT 的体外流动模型中，组织爆破是否增强了重组组织纤溶酶原激活剂（rt-PA）对高度回缩的猪血栓的溶栓作用。
用导管定向生理盐水（阴性对照）、rt-PA（溶栓对照）、组织爆破、DEFINITY 和 rt-PA 联合组织爆破或 rt-PA 联合组织爆破联合或不联合DEFINITY 处理高度回缩的猪全血血栓 1 小时。应用 5 个周期、1.5MHz 的组织爆破脉冲，其峰值负压为 33.2MPa，脉冲重复频率为 40Hz。在组织爆破照射期间采集 B 模式和被动空化图像，以监测气泡活动。
接受有或没有 rt-PA 的组织爆破治疗的血栓显示出比对照物更高的溶栓效果（7.0%的血流恢复或更低），并且 rt-PA 联合组织爆破比组织爆破联合生理盐水更有效（86.1±10.2%的血流恢复与 61.7±19.8%的血流恢复相比）。在有或没有 rt-PA 的情况下，DEFINITY 的添加并没有增强溶栓效果或空化剂量。空化剂量通常与溶栓效果无关。
在生理流动的情况下，使用组织爆破，有或没有导管定向 rt-PA，可增强溶栓效果。这表明这些治疗方法可能是治疗 DVT 的有效方法。
