Successful microbubble sonothrombolysis without tissue-type plasminogen activator in a rabbit model of acute ischemic stroke.
Successful microbubble sonothrombolysis without tissue-type plasminogen activator in a rabbit model of acute ischemic stroke.
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DOI：
10.1161/strokeaha.110.607150
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发表时间：
2011-08
期刊：
影响因子：
8.3
通讯作者：
Borrelli MJ
中科院分区：
文献类型：
--
作者：
Culp WC;Flores R;Brown AT;Lowery JD;Roberson PK;Hennings LJ;Woods SD;Hatton JH;Culp BC;Skinner RD;Borrelli MJ
微泡（MB）结合超声（US）已被证明在体外和体内溶解凝块，而无需组织纤溶酶原激活剂（tPA）。我们使用兔栓塞性卒中模型评价了三种类型MB的超声溶栓。新西兰白色家兔（n=74）接受颈内动脉血管造影栓塞单个3日龄圆柱形凝块（0.6×4.0 mm）。团体包括：1）对照组（n=11）栓塞，未治疗，2）tPA（n=20），3）tPA+US（n=10），4）Perflutren Lipid MB+US（n=16），5）白蛋白3µm MB+US（n=8）和6）标记白蛋白3µm MB+US（n=9）。栓塞后1小时开始治疗。超声为脉冲波（1 MHz; 0.8 W/cm 2）1小时; tPA家兔在1小时内静脉注射tPA（0.9 mg/kg）。在30分钟内静脉注射脂质MB剂量（0.16 mg/kg）。3µm MB的剂量为5×109 MB单独静脉注射或用依替巴肽和纤维蛋白抗体标记，持续30分钟。在24小时时对家兔实施安乐死。使用脑切片上的活体染色确定脑体积。在H&E切片上评价出血。与对照组（3.5%±0.8%）相比，脂质MB+US（1.0%±0.6%; P=0.013）、3µm MB+US（0.7%±0.9%; P=0.018）和标记3µm MB+US（0.8%±0.8%; P=0.019）处理组家兔的CT体积百分比较低。三种MB类型总体上具有比对照组更低的梗死体积（P=0.0043）。单纯tPA组和tPA+US组的平均脑体积分别为2.2%±0.6%和1.7%±0.8%（P=NS）。不使用tPA的超声溶栓使用这些MB在减少梗死体积方面是有效的。人类应用研究和进一步的MB技术开发是合理的。
Microbubbles (MB) combined with ultrasound (US) have been shown to lyse clots without tissue plasminogen activator (tPA) both in vitro and in vivo. We evaluated sonothrombolysis with three types of MB using a rabbit embolic stroke model. New Zealand White rabbits (n=74) received internal carotid angiographic embolization of single 3 day-old cylindrical clots (0.6×4.0-mm). Groups included: 1) control (n=11) embolized without treatment, 2) tPA (n=20), 3) tPA+US (n=10), 4) Perflutren Lipid MB+US (n=16), 5) albumin 3µm MB+US (n=8), and 6) tagged albumin 3µm MB+US (n=9). Treatment began 1 hour post-embolization. Ultrasound was pulsed-wave (1 MHz; 0.8 W/cm2) for 1 hour; rabbits with tPA received intravenous tPA (0.9 mg/kg) over 1 hour. Lipid MB dose was intravenous (0.16 mg/kg) over 30 minutes. Dosage of 3µm MB was 5×109 MB intravenously alone or tagged with eptifibatide and fibrin antibody over 30 minutes. Rabbits were euthanized at 24 hours. Infarct volume was determined using vital stains on brain sections. Hemorrhage was evaluated on H&E sections. Infarct volume percent was lower for rabbits treated with Lipid MB+US (1.0%±0.6%; P=0.013), 3µm MB+US (0.7%±0.9%; P=0.018), and tagged 3µm MB+US (0.8%±0.8%; P=0.019) compared with controls (3.5%±0.8%). The three MB types collectively had lower infarct volumes (P=0.0043) than controls. Infarct volume averaged 2.2%±0.6% and 1.7%±0.8% for rabbits treated with tPA alone and tPA+US, respectively (P=NS). Sonothrombolysis without tPA using these MB is effective in decreasing infarct volumes. Study of human application and further MB technique development are justified.