title: Tissue plasminogen activator concentration dependence of 120 kHz ultrasound-enhanced thrombolysis.
abstract: It has been known for some time that the application of ultrasound can enhance the efficacy of thrombolytic medications such as recombinant tissue plasminogen activator (rt-PA). Potential clinical applications of this ultrasound-enhanced thrombolysis (UET) include the treatment of myocardial infarction, acute ischemic stroke, deep venous thrombosis and other thrombotic disorders. It may be possible to reduce the dose of rt-PA while maintaining lytic efficacy; however there is little data on the rt-PA concentration dependence of UET. In this work, the rt-PA concentration dependence of clot lysis resulting from 120 kHz UET exposure was measured in an in vitro human clot model. Clots were exposed to rt-PA for 30 min, with (UET treated) or without 120 kHz ultrasound (rt-PA treated) at 37 degrees C, and the clot width measured as a function of time. The rt-PA concentration ranged from 0-10 microg/mL. The initial lytic rate for the UET-treated group was greater than that of the rt-PA group at almost all rt-PA concentrations, and exhibited a maximum over concentration values of 1-3 microg/mL.
authors.affiliation: Department of Emergency Medicine, University of Cincinnati College ofMedicine, Cincinnati, OH 45267-0769, USA. shawge@ucmail.uc.edu
authors.forename: George J
authors.initials: GJ
authors.lastname: Shaw
authors.forename: Jason M
authors.initials: JM
authors.lastname: Meunier
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lindsell
authors.forename: Christy K
authors.initials: CK
authors.lastname: Holland
mesh_terms: D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D011994:Recombinant Proteins / Q000008:administration & dosage; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D014464:Ultrasonic Therapy / Q000379:methods*; D014463:Ultrasonography
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator