Behrens S, Spengos K, Daffertshofer M, Wirth S, Hennerici M
Department of Neurology, University of Heidelberg, University Hospital Mannheim, Theodor-Kutzer-Ufer, 68135 Mannheim, Germany.
Echocardiography. 2001 Apr;18(3):259-63. doi: 10.1046/j.1540-8175.2001.00259.x.
Systemic treatment with rtPA approved for a 3-hour window is the only established causal therapy for acute stroke in the United States and Canada. Thrombolytic therapy with rtPA demonstrated a small, although significantly reduced morbidity, in a limited number of highly selected patients. As recently shown, intraarterial application is favorable and opens the window of treatment up to 6 hours. The combination of ultrasound with thrombolytic agents may further enhance the potential benefit by means of enzymatic-mediated thrombolysis, which has been demonstrated in different in vitro and in vivo experiments for an accelerated recanalization of occluded peripheral and coronary vessels. Whereas no or only small attenuation of ultrasound can be expected through skin and chest, intensity will be significantly attenuated if penetration of the skull is required. The transcranial penetration of ultrasound increases when the frequency is decreased to 20 kHz and may be transmitted through the skull transtemporally with tolerable attenuation up to 200 kHz. This results in efficacy in vitro with low intensities of 0.5-2.0 W/cm(2) systemic treatment with rtPA approved for a 3-hour window in the nonfocused ultrasound field. Application of ultrasound insonation increased rtPA-mediated thrombolysis up to 20% in a static model; meanwhile, it enhanced the recanalization rate from 30%-90% in a flow model. In vitro results suggest that 1 MHz ultrasound with 0.5 W/cm(2), established for diagnostic purposes, may already enhance rtPA- mediated thrombolysis. Before therapeutic ultrasound can be tested clinically in acute stroke, safety of transcranial exposure of the brain has to be confirmed. To date, animal experiments suggested no harm to the blood brain barrier or systemic heating with 2 W/cm(2). This combined treatment is one perspective in optimizing therapy in acute stroke within the acute phase and may be applied easily with few limitations.
在美国和加拿大，经批准用于3小时时间窗的rtPA全身治疗是急性卒中唯一已确立的因果疗法。rtPA溶栓治疗在少数经过严格挑选的患者中显示出虽小但显著降低的发病率。最近的研究表明，动脉内应用是有利的，并且将治疗时间窗延长至6小时。超声与溶栓剂联合使用可能通过酶介导的溶栓作用进一步提高潜在益处，这在不同的体外和体内实验中已得到证实，可加速闭塞的外周血管和冠状动脉再通。虽然预计超声通过皮肤和胸部时不会衰减或仅有轻微衰减，但如果需要穿透颅骨，强度将显著衰减。当频率降至20kHz时，超声的经颅穿透增加，并且在高达200kHz时可以以可耐受的衰减经颞部穿过颅骨进行传输。这导致在非聚焦超声场中，0.5 - 2.0W/cm²的低强度全身rtPA治疗在体外具有疗效。在静态模型中，超声照射使rtPA介导的溶栓作用提高了20%；同时，在血流模型中，它将再通率从30%提高到了90%。体外结果表明，用于诊断目的的1MHz、0.5W/cm²的超声可能已经增强了rtPA介导的溶栓作用。在治疗性超声能够在急性卒中中进行临床测试之前，必须确认脑部经颅暴露的安全性。迄今为止，动物实验表明，2W/cm²的超声对血脑屏障无害或不会引起全身发热。这种联合治疗是优化急性卒中急性期治疗的一个方向，并且应用起来限制很少。
