Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD 20892, USA.
J Vasc Interv Radiol. 2012 Jul;23(7):953-961.e2. doi: 10.1016/j.jvir.2012.04.001. Epub 2012 May 19.
Prosthetic arteriovenous or arterial-arterial bypass grafts can thrombose and be resistant to revascularization. A thrombosed bypass graft model was created to evaluate the potential therapeutic enhancement and safety profile of pulsed high-intensity-focused ultrasound (pHIFU) on pharmaceutical thrombolysis.
In swine, a right carotid-carotid expanded polytetrafluoroethylene bypass graft was surgically constructed, containing a 40% stenosis at its distal end to induce graft thrombosis. The revascularization procedure was performed 7 days after surgery. After model development and dose response experiments (n = 11), two cohorts were studied: pHIFU with tissue plasminogen activator (TPA; n = 4) and sham pHIFU with TPA (n = 3). The experiments were identical in both groups except no energy was delivered in the sham pHIFU group. Serial angiograms were obtained in all cases. The area of graft opacified by contrast medium on angiograms was quantified with digital image processing software. A blinded reviewer calculated the change in the graft area opacified by contrast medium and expressed it as a percentage, representing percentage of thrombolysis.
Combining pHIFU with 0.5 mg of TPA resulted in a 52% ± 4% increase in thrombolysis on angiograms obtained at 30 minutes, compared with a 9% ± 14% increase with sham pHIFU and 0.5 mg TPA (P = .003). Histopathologic examination demonstrated no differences between the groups.
Thrombolysis of occluded bypass grafts was significantly increased when combining pHIFU and TPA versus sham pHIFU and TPA. These results suggest that application of pHIFU may augment thrombolysis with a reduced time and dose.
人工动静脉或动脉-动脉旁路移植血管可能发生血栓形成，且难以再通。本研究建立了血栓形成的旁路移植血管模型，以评估脉冲高强度聚焦超声（pHIFU）增强药物溶栓的潜在治疗效果和安全性。
在猪中，通过手术构建了右侧颈总动脉-颈总动脉膨体聚四氟乙烯旁路移植血管，其远端含有 40%狭窄以诱导移植血管血栓形成。在手术后 7 天进行再通程序。在模型建立和剂量反应实验（n = 11）后，研究了两组：组织型纤溶酶原激活剂（tissue plasminogen activator，TPA）联合 pHIFU（n = 4）和 TPA 联合 sham pHIFU（n = 3）。两组实验除 sham pHIFU 组不输送能量外，其余操作均相同。所有病例均进行了连续血管造影。使用数字图像处理软件对血管造影中对比剂充盈的移植血管区域进行定量分析。一位盲法观察者计算了对比剂充盈的移植血管区域的变化，并表示为溶栓百分比。
在 30 分钟时，与 sham pHIFU 联合 0.5 mg TPA 组（9%±14%）相比，pHIFU 联合 0.5 mg TPA 组的溶栓百分比增加了 52%±4%（P =.003）。组织病理学检查显示两组之间无差异。
与 sham pHIFU 联合 TPA 相比，pHIFU 联合 TPA 可显著增加闭塞旁路移植血管的溶栓。这些结果表明，应用 pHIFU 可能会在减少时间和剂量的情况下增强溶栓效果。
