微泡增强超声溶栓减少兔急性缺血性脑卒中模型的颅内出血。
Microbubble-augmented ultrasound sonothrombolysis decreases intracranial hemorrhage in a rabbit model of acute ischemic stroke.
机构信息
Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
出版信息
Invest Radiol. 2011 Jul;46(7):419-24. doi: 10.1097/RLI.0b013e31820e143a.
OBJECTIVES
Increasing evidence confirms that 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.
MATERIALS AND METHODS
Rabbits (n = 158) received a 1.0-mm clot, angiographically injected into the internal carotid artery causing infarcts. Rabbits were randomized to 6 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). US groups received pulsed wave US (1 MHz, 0.8 W/cm) 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 killed 24 hours later and infarct volume and incidence, location, and severity of ICH were determined by histology and pathologic examination.
RESULTS
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%).
CONCLUSIONS
Treatment with MB + US after embolization decreased the incidence of ICH and efficacy was similar to tPA in reducing infarct volume.
目的
越来越多的证据证实，微泡（MB）增强超声（US）溶栓可增强有或无组织型纤溶酶原激活物（tPA）的血栓溶解。颅内出血（ICH）是急性缺血性卒中使用 tPA 的主要并发症。我们定量评估了 tPA 溶栓和 MB+US 治疗相关的 ICH 发生率，并在急性缺血性卒中兔模型中比较了梗死体积。
材料和方法
兔子（n=158）接受 1.0mm 血栓，经血管造影注入颈内动脉引起梗死。兔子随机分为 6 个实验组，包括（1）对照组（n=50），不进行治疗，栓塞；（2）US 组（n=18）；（3）仅 tPA 组（n=27）；（4）tPA+US 组（n=22）；（5）MB+US 组（n=27）；（6）tPA+MB+US 组（n=14）。US 组接受脉冲波 US（1MHz，0.8W/cm）治疗 1 小时；tPA 组兔接受静脉 tPA（0.9mg/kg）治疗 1 小时。MB 组兔接受静脉 MB（0.16mg/kg）治疗 30 分钟。24 小时后处死兔子，通过组织学和病理检查确定梗死体积和 ICH 的发生率、位置和严重程度。
结果
与 tPA+US（73%）、US 组（56%）、仅 tPA 组（48%）、tPA+MB+US（36%）和对照组（36%）相比，MB+US 组（19%）的兔子发生梗死区外 ICH 的比例显著降低（P=0.004）。梗死区内 ICH 的发生率和严重程度无差异（P>0.39）。接受 US 治疗的兔子的梗死体积显著增大（P=0.002），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%）；这些治疗方法共同作用，不包括 US 组，与对照组（0.45%±0.10%）相比有差异（P=0.03）。
结论
栓塞后 MB+US 治疗可降低 ICH 的发生率，其降低梗死体积的效果与 tPA 相似。
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