Microbubble-Augmented Ultrasound Sonothrombolysis Decreases Intracranial Hemorrhage in a Rabbit Model of Acute Ischemic Stroke

被引：51

作者：

Flores, Rene ^{[1
]}

Hennings, Leah J. ^{[2
]}

Lowery, John D. ^{[3
]}

Brown, Aliza T. ^{[1
]}

Culp, William C. ^{[1
]}

机构：

[1] Univ Arkansas Med Sci, Dept Radiol, Little Rock, AR 72205 USA

[2] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA

[3] Univ Arkansas Med Sci, Div Lab Anim Med, Little Rock, AR 72205 USA

来源：

INVESTIGATIVE RADIOLOGY | 2011年 / 46卷 / 07期

关键词：

hemorrhage; ischemic stroke; microbubbles; thrombolysis; ultrasound; TISSUE-PLASMINOGEN-ACTIVATOR; CEREBRAL-ARTERY OCCLUSION; LOW-FREQUENCY ULTRASOUND; TRANSCRANIAL ULTRASOUND; 2-MHZ ULTRASOUND; CLOT LYSIS; THROMBOLYSIS; FIBRINOLYSIS; THERAPY; TRIAL;

D O I：

10.1097/RLI.0b013e31820e143a

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

100231 [临床病理学]; 100902 [航空航天医学];

摘要：

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(2)) 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.

引用

页码：419 / 424

页数：6

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