Culp William C, Porter Thomas R, Lowery John, Xie Feng, Roberson Paula K, Marky Louis
Department of Radiology, University of Arkansas for Medical Sciences, 4301 W Markham St, Slot 556, Little Rock, AR 72205-7199, USA.
Stroke. 2004 Oct;35(10):2407-11. doi: 10.1161/01.STR.0000140890.86779.79. Epub 2004 Aug 19.
Destruction of microbubbles by transcutaneous low-frequency ultrasound (LFUS) has been used to lyse adjacent clot and recanalize acutely thrombosed vessels. LFUS with intraarterial microbubbles has been shown to lyse cerebral clot rapidly in pigs without thrombolytic drugs. We hypothesized that intravenous platelet-targeted microbubbles with LFUS may be a rapid noninvasive technique to recanalize thrombosed intracerebral vessels.
After angiography, 0.5 cc of autogenous thrombus was injected into 1 ascending pharyngeal artery of a pig, occluding it and the rete mirabile. These vessels connect the carotid to the internal carotid and are the main cerebral blood supply. Saline control or intravenous decafluorobutane-sonicated dextrose albumin microbubbles tagged with a subtherapeutic quantity of glycoprotein 2b/3a receptor inhibitor eptifibatide (75 U/kg plus 12 cc of microbubbles administered over 21 minutes), or eptifibatide control, was given with transcutaneous temporal LFUS (1 MHz at 2.0 W/cm2) for 24 minutes. Angiography followed with scoring of declotting and flow. The same protocol was repeated on the contralateral side with the other test fluid so each animal received a saline control and either tagged microbubble or eptifibatide alone.
Fifteen pigs completed the protocol with a mean clot age of 4.6 hours. Using tagged microbubbles, 6 of 8 achieved success compared with 0 of 7 receiving eptifibatide alone (P=0.007) and 1 of 15 receiving saline alone (P=0.02).
Intravenous platelet-targeted microbubbles combined with transcranial LFUS can rapidly open acute intracranial thrombotic occlusions. Further development for ischemic stroke therapy is justified.
经皮低频超声（LFUS）破坏微泡已被用于溶解相邻的血栓并使急性血栓形成的血管再通。已证明在猪体内，动脉内注射微泡的低频超声在无溶栓药物的情况下可迅速溶解脑内血栓。我们推测，静脉注射靶向血小板的微泡并联合低频超声可能是一种使脑内血栓形成的血管再通的快速非侵入性技术。
血管造影后，将0.5 cc自体血栓注入猪的1条咽升动脉，阻塞该动脉及奇网。这些血管连接颈总动脉和颈内动脉，是主要的脑供血血管。给予生理盐水对照或静脉注射用亚治疗剂量的糖蛋白2b/3a受体抑制剂依替巴肽（75 U/kg加12 cc微泡，在21分钟内给药）标记的十氟丁烷超声处理的葡萄糖白蛋白微泡，或依替巴肽对照，并进行经皮颞部低频超声（1 MHz，2.0 W/cm2）照射24分钟。随后进行血管造影，并对血栓溶解和血流情况进行评分。在对侧用另一种测试液重复相同方案，因此每只动物接受生理盐水对照以及单独的标记微泡或依替巴肽。
15头猪完成了该方案，血栓平均形成时间为小时。使用标记微泡时，8只中有6只成功，而单独接受依替巴肽的7只中无1只成功（P = 0.007），单独接受生理盐水的15只中有1只成功（P = 0.02）。
静脉注射靶向血小板的微泡联合经颅低频超声可迅速开通急性颅内血栓性闭塞。缺血性卒中治疗的进一步研发是合理的。
