Siegel R J, Atar S, Fishbein M C, Brasch A V, Peterson T M, Nagai T, Pal D, Nishioka T, Chae J S, Birnbaum Y, Zanelli C, Luo H
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Echocardiography. 2001 Apr;18(3):247-57. doi: 10.1046/j.1540-8175.2001.00247.x.
Previous studies have shown that external ultrasound with low frequencies and high intensities can enhance thrombolytic drug-induced clot dissolution during in vitro experiments. In this series of studies, we evaluated the efficacy of peripheral and coronary thrombolysis in vivo in animals by using noninvasive transcutaneous ultrasound combined with thrombolytic drugs (streptokinase and tPA) and/or microbubbles agents (dodecafluoropentane [DDFP] and perfluorocarbon-exposed sonicated dextrose albumin [PESDA]). Thrombotic occlusions were induced in 74 rabbit iliofemoral arteries and 24 canine left anterior descending (LAD) coronary arteries in this in vivo study. By using the combination of transcutaneous ultrasound and streptokinase, the angiographic patency rate in rabbit iliofemoral arteries was higher (56%-100%) than with ultrasound (6%; P < or = 0.0036) and streptokinase alone (6%; P < or = 0.0012). Also, with transcutaneous ultrasound and microbubbles, the angiographic patency rates were 76%-100% as compared with ultrasound alone (0%, P < or = 0.0003) or microbubbles alone (9%, P < or = 0.0001). In the canine study of acute myocardial infarction, thrombolysis in myocardial infarction (TIMI) grade flow at 90 minutes in the tPA alone group was 0.92 +/- 1.4 as compared with 2.42 +/- 1.9 in the tPA plus transthoracic ultrasound group (P = 0.006). There was much improved reperfusion with tPA plus ultrasound as compared with tPA alone. In vivo animal studies demonstrate that noninvasive transcutaneous ultrasound can greatly enhance the effect of clot dissolution with thrombolytic drugs and/or microbubbles, and has the potential for clinical application as an adjunctive method to improve arterial thrombolysis.
先前的研究表明，在体外实验中，低频高强度的体外超声可增强溶栓药物诱导的血栓溶解。在这一系列研究中，我们通过使用无创经皮超声联合溶栓药物（链激酶和组织型纤溶酶原激活剂[tPA]）和/或微泡剂（十二氟戊烷[DDFP]和全氟碳暴露超声处理葡萄糖白蛋白[PESDA]），评估了动物体内外周和冠状动脉溶栓的疗效。在这项体内研究中，74只兔的髂股动脉和24只犬的左前降支（LAD）冠状动脉被诱导形成血栓闭塞。通过经皮超声和链激酶联合使用，兔髂股动脉的血管造影通畅率（56%-100%）高于单独使用超声（6%；P≤0.0036）和单独使用链激酶（6%；P≤0.0012）。此外，经皮超声和微泡联合使用时，血管造影通畅率为76%-100%，而单独使用超声时为0%（P≤0.0003），单独使用微泡时为9%（P≤0.0001）。在犬急性心肌梗死研究中，单独使用tPA组90分钟时心肌梗死溶栓（TIMI）血流分级为0.92±1.4，而tPA加经胸超声组为2.42±1.9（P=0.006）。与单独使用tPA相比，tPA加超声时再灌注有显著改善。体内动物研究表明，无创经皮超声可大大增强溶栓药物和/或微泡的血栓溶解效果，作为一种辅助方法改善动脉溶栓具有临床应用潜力。
