From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
Stroke. 2016 May;47(5):1344-53. doi: 10.1161/STROKEAHA.115.012056. Epub 2016 Apr 5.
Microthrombi originating from disintegrated clots or formed in situ may account for the poor clinical improvement of acute ischemic stroke after recanalization therapy. We attempted to determine whether microbubble-mediated sonothrombolysis could dissolve platelet-rich and erythrocyte-rich microthrombi, thereby reducing their brain injury-causing potential.
Platelet- and erythrocyte-rich microthrombosis were induced by periadventitial application of 5% ferric chloride or thrombin to mesenteric microvessels in 75 Sprague-Dawley rats. Acute ischemic stroke was induced by intracarotid injection of platelet- or erythrocyte-rich microthrombi in another 50 rats. Rats were randomly divided into control (CON), ultrasound (US), ultrasound and microbubble (US+MB), recombinant tissue-type plasminogen activator (r-tPA), and US+MB+r-tPA groups. The post-treatment mesenteric microvessel recanalization rates, cerebral infarct volumes, and neurological scores were determined.
The recanalization rates of platelet- and erythrocyte-rich microthrombi in mesenteric microvessels were higher (P<0.05), and the cerebral infarct volumes and neurological scores of rats with either microthrombi were lower in the US+MB group than in the CON group (P<0.01). The infarct volumes and neurological scores were greater in the r-tPA group than in the US+MB and US+MB+r-tPA groups after treatment of rats with platelet-rich microthrombi (P<0.05). In contrast, after treatment of rats with erythrocyte-rich microthrombi, the infarct volumes and neurological scores were similar in the r-tPA and US+MB groups, but smaller in the US+MB+r-tPA group (P<0.05).
Microbubble-mediated sonothrombolysis improved the outcomes of microthrombi-induced acute ischemic stroke. Thus, this method may serve as an attractive adjunct to recanalization therapy for acute ischemic stroke.
源自于已分解的血栓或原位形成的微血栓可能导致急性缺血性卒中患者在接受再通治疗后的临床改善不佳。我们试图确定微泡介导的声溶栓是否可以溶解富含血小板和富含红细胞的微血栓，从而降低其导致脑损伤的可能性。
通过在肠系膜微血管周围应用 5%的三氯化铁或凝血酶诱导富含血小板和富含红细胞的微血栓形成。在另外 50 只大鼠中通过颅内注射富含血小板和富含红细胞的微血栓来诱导急性缺血性卒中。将大鼠随机分为对照组（CON）、超声组（US）、超声联合微泡组（US+MB）、重组组织型纤溶酶原激活剂组（r-tPA）和超声联合微泡+重组组织型纤溶酶原激活剂组（US+MB+r-tPA）。测定治疗后的肠系膜微血管再通率、脑梗死体积和神经功能评分。
肠系膜微血管中富含血小板和富含红细胞的微血栓的再通率较高（P<0.05），US+MB 组大鼠的脑梗死体积和神经功能评分均低于 CON 组（P<0.01）。治疗富含血小板的微血栓大鼠后，r-tPA 组的梗死体积和神经功能评分均高于 US+MB 组和 US+MB+r-tPA 组（P<0.05）。相反，治疗富含红细胞的微血栓大鼠后，r-tPA 组和 US+MB 组的梗死体积和神经功能评分相似，但 US+MB+r-tPA 组的梗死体积和神经功能评分较小（P<0.05）。
微泡介导的声溶栓改善了微血栓诱导的急性缺血性卒中的预后。因此，该方法可能成为急性缺血性卒中再通治疗的一种有吸引力的辅助手段。
