title: Acceleration of thrombolysis with ultrasound through the cranium in a flow model.
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.
authors.affiliation: Department of Neurology, University of Heidelberg, Universitätsklinikum Mannheim, 68135, Mannheim, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Spengos
authors.forename: S
authors.initials: S
authors.lastname: Behrens
authors.forename: M
authors.initials: M
authors.lastname: Daffertshofer
authors.forename: C E
authors.initials: CE
authors.lastname: Dempfle
authors.forename: M
authors.initials: M
authors.lastname: Hennerici
mesh_terms: D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D019047:Phantoms, Imaging; D010960:Plasminogen Activators / Q000627:therapeutic use*; D011994:Recombinant Proteins; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D011994:Recombinant Proteins; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator