Microbubble-augmented ultrasound sonothrombolysis decreases intracranial hemorrhage in a rabbit model of acute ischemic stroke.
Microbubble-augmented ultrasound sonothrombolysis decreases intracranial hemorrhage in a rabbit model of acute ischemic stroke.
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在急性缺血性中风的兔模型中，微泡超声的超声Sonothrombolsy减少了颅内出血。
DOI：
10.1097/rli.0b013e31820e143a
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发表时间：
2011-07
影响因子：
6.7
通讯作者：
Culp WC
中科院分区：
文献类型：
--
作者：
Flores R;Hennings LJ;Lowery JD;Brown AT;Culp WC
越来越多的证据证实，无论是否使用组织纤溶酶原激活剂(TPA)，微泡(MB)增强超声(US)溶栓都能增强血栓溶解。颅内出血(ICH)是影响tPA在急性缺血性卒中应用的主要并发症。我们量化了与tPA溶栓和MB+US治疗相关的脑出血的发生率，并比较了急性缺血性中风兔模型的脑梗塞体积。兔(n=158)接受血管造影术向颈内动脉注射1.0 mm的血栓，造成脑梗塞。将兔随机分为6组：对照组(n=50)，未经治疗的栓塞组，超声(n=18)，单纯tPA(n=27)，tPA+US(n=22)，MB+US(n=27)，tPA+MB+US(n=14)。超声组给予脉冲超声(1 MHz，0.8W/cm2)1h，tPA组静脉注射tPA(0.9 mg/kg)1h。MB兔静脉注射MB(0.16 mg/kg)30分钟以上。24小时后处死动物，通过组织学和病理学检查确定脑梗塞的体积、发生率、部位和严重程度。MB+US(19%)组兔脑梗塞灶外出血发生率显著低于tPA+US组(73%)、单纯US组(56%)、tPA组(48%)、tPA+MB+US组(36%)和对照组(36%)。梗死灶内脑出血的发生率和严重程度没有差别(P>；0.39)。心肌梗死体积US组(0.97±0.17%)显著大于MB+US组(0.20±0.14%)、tPA+US组(0.15±0.16%)、tPA组(0.14±0.14%)和tPA+MB+US组(0.10±20%)(P=0.002)。MB+US治疗可降低脑出血的发生率，在缩小脑梗塞体积方面的疗效与tPA相似。
Increasing evidence confirms microbubble (MB) augmented ultrasound (US) thrombolysis enhances clot lysis with or without tissue plasminogen activator (tPA). Intracranial hemorrhage (ICH) is a major complication militating against tPA use in acute ischemic stroke. We quantified the incidence of ICH associated with tPA thrombolysis and MB+US therapy and compared infarct volumes in a rabbit model of acute ischemic stroke. Rabbits (n=158) received a 1.0-mm clot angiographically injected into the internal carotid artery causing infarcts. Rabbits were randomized to six test groups including: 1) control (n=50), embolized without therapy, 2) US (n=18), 3) tPA only (n=27), 4) tPA+US (n=22), 5) MB+US (n=27), and 6) tPA+MB+US (n=14). Ultrasound groups received pulsed wave US (1 MHz, 0.8 W/cm2) for 1 hour; rabbits with tPA received intravenous tPA (0.9 mg/kg) over 1 hour. Rabbits with MB received intravenous MB (0.16 mg/kg) given over 30 minutes. Rabbits were sacrificed 24 hours later and infarct volume and incidence, location, and severity of ICH were determined by histology and pathological examination. Percentage of rabbits having ICH outside the infarct area was significantly decreased (P=0.004) for MB+US (19%) rabbits compared with tPA+US (73%), US only (56%), tPA (48%), tPA+MB+US (36%), and control (36%) rabbits. Incidence and severity of ICH within the infarct did not differ (P>0.39). Infarct volume was significantly greater (P=0.002) for rabbits receiving US (0.97±0.17%) than for MB+US (0.20±0.14%), tPA+US (0.15±0.16%), tPA (0.14±0.14%), and tPA+MB+US (0.10±20%) rabbits; these treatments collectively, excluding US only, differed (P=0.03) from control (0.45±0.10%). Treatment with MB+US following embolization decreased the incidence of ICH and efficacy was similar to tPA in reducing infarct volume.