Alexandrov Andrei V
Department of Neurology and Radiology, Houston Medical School, The University of Texas, MSB 7044-6431 Fannin Street, Houston, TX 77030, USA.
Eur J Ultrasound. 2002 Nov;16(1-2):131-40. doi: 10.1016/s0929-8266(02)00040-x.
In the pivotal clinical trials of intravenous tissue plasminogen activator (TPA) therapy for ischemic stroke, a low rate of early arterial recanalization was suspected due to the small numbers of patients who had early dramatic clinical improvement. TPA activity can be enhanced with ultrasound including 2 MHz transcranial Doppler (TCD). TCD can identify residual signals around the thrombus with the thrombolysis in brain ischemia (TIBI) flow grading system and therefore expose more thrombus surface to circulating TPA. A phase I clinical study, monitoring TPA infusion with diagnostic ultrasound resulted in an unexpectedly high rate of complete recanalization (36% of proximal middle cerebral artery (MCA) occlusions) and associated early dramatic clinical recovery (24%) among treated patients. The external application of diagnostic ultrasound in our studies raised the possibility that a synergistic TPA and ultrasound action accelerated flow improvement and achieved faster and more complete thrombus dissolution as predicted from experimental models. The CLOTBUST (combined lysis of thrombus in brain ischemia using transcranial ultrasound and systemic TPA) trial is testing this hypothesis in a phase II clinical randomized multi-center setting. Dramatic clinical recovery from stroke and complete recanalization shortly after TPA bolus are feasible goals for thrombolysis assisted with TCD monitoring.
在静脉注射组织型纤溶酶原激活剂（TPA）治疗缺血性中风的关键临床试验中，由于早期临床显著改善的患者数量较少，怀疑早期动脉再通率较低。包括2兆赫经颅多普勒（TCD）在内的超声可增强TPA活性。TCD可通过脑缺血溶栓（TIBI）血流分级系统识别血栓周围的残余信号，从而使更多血栓表面暴露于循环中的TPA。一项I期临床研究，用诊断性超声监测TPA输注，结果在治疗患者中出现了意外高的完全再通率（大脑中动脉（MCA）近端闭塞患者中有36%）以及相关的早期显著临床恢复（24%）。在我们的研究中，诊断性超声的外部应用提出了一种可能性，即TPA与超声协同作用加速了血流改善，并如实验模型所预测的那样实现了更快、更完全的血栓溶解。CLOTBUST（使用经颅超声和全身TPA联合溶解脑缺血血栓）试验正在II期临床随机多中心研究中验证这一假设。在TPA推注后不久，中风患者实现显著临床恢复和完全再通是TCD监测辅助溶栓的可行目标。
