Abstract
Thrombolysis is an efficient therapy for hyperacute stroke within a limited time window. Neurological outcome depends on the recanalization time of the occluded vessel. Nonthermal effects of low-frequency ultrasound (US) accelerate enzymatic fibrinolysis in vitro. We examined the effects of transcranially applied US on recombinant tissue plasminogen activator (rt-PA)-mediated thrombolysis in a flow model in vitro. Pure fibrin clots were placed in a continuous-pressure flow model and treated with rt-PA during 1-MHz US exposure (0.5 W/cm 2; spatial peak, temporal peak intensity). Transcranial and direct US application in combination with rt-PA significantly ( p < 0.001) shortened recanalization time, increased perfusion flow and reperfusion rate in comparison with rt-PA-mediated thrombolysis alone. Recanalization rate within 30 min was 90–100% in the US-exposed clots vs. 30% in the clots treated only with rt-PA. Our results suggest that transcranial application of 1-MHz US may accelerate reperfusion and recanalization rate of occluded intracerebral vessels by enhancing rt-PA-mediated thrombolysis. Shortening of recanalization time could contribute to optimizing effects of acute thrombolytic stroke therapy.
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