Abstract

The key goal in the treatment of acute ischemic stroke is fast vessel recanalization. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is efficient in humans but mean time for recanalization is within hours. Ultrasound bio-effects has been shown to facilitate rt-PA mediated thrombolysis in peripheral arteries. We used an embolic stroke model in the rat. In all rats we induced an ischemic stroke by a selective occlusion of the middle cerebral artery with whole blood clots. From an entire collective of 54 rats 47 completed the protocol ( n=7 died early). Four different groups (no treatment n=6; full dose rt-PA treatment only [10 mg/kg per body weight] n=14, half dose rt-PA treatment plus ultrasound n=10, and full dose rt-PA treatment plus ultrasound n=17) were investigated. We found a significant reduction of absolute as well as relative infarct volume in the full dose rt-PA plus ultrasound group (81±72 mm 3; P<0.05) in comparison to untreated rats (253±159 mm 3; P<0.05) as well as in comparison to rats treated with full dose rt-PA only (167±91 mm 3; P<0.05). There were five intracranial bleedings giving a bleeding rate of 9.3%. In summary: ultrasound treatment in addition to rt-PA is more effective than single rt-PA treatment in reducing infarct volume and safe with regard to bleeding.

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