Acceleration of thrombolysis with ultrasound through the cranium in a flowmodel

Thrombolysis is an efficient therapy for hyperacute stroke within a limited time window, Neurological outcome depends on the recanalization time of th e occluded vessel. Nonthermal effects of low-frequency ultrasound (US) acce lerate enzymatic fibrinolysis in vitro. We examined the effects of transcra nially applied US on recombinant tissue plasminogen activator (rt-PA)-media ted thrombolysis in a how model in vitro, Pure fibrin clots were placed in a continuous-pressure flow model and treated with rt-PA during 1-MHz US exp osure (0.5 W/cm(2); spatial peak, temporal peak intensity). Transcranial an d direct US application in combination with rt-PA significantly (p < 0.001) shortened recanalization time, increased perfusion flow and reperfusion ra te in comparison with rt-PA-mediated thrombolysis alone. Recanalization rat e within 30 min was 90-100% in the US-exposed clots vs. 30% in the clots tr eated only with rt-PA. Our results suggest that transcranial application of 1-MHz US may accelerate repel fusion and recanalization rate of occluded i ntracerebral vessels by enhancing rt-PA-mediated thrombolysis, Shortening o f recanalization time could contribute to optimizing effects of acute throm bolytic stroke therapy. (C) 2000 World Federation for Ultrasound in Medicin e & Biology.