title: Effect of ultrasound on tissue-type plasminogen activator-induced thrombolysis.
abstract: BACKGROUND
  The efficacy of fibrinolytic therapy is limited by the small surface area of the clot that is available for the binding of the thrombolytic agent, such as tissue-type plasminogen activator (t-PA). We hypothesized that exposure of the clot to ultrasound during thrombolytic treatment could enhance lysis through perturbation of the thrombus, which would expose additional fibrin binding sites for t-PA.
  
  
  RESULTS
  Whole human blood clots containing radiolabeled fibrinogen were incubated in vitro for 200 minutes with Tris-albumin buffer containing t-PA at concentrations ranging from 3 to 3,000 IU/ml. In paired experiments, one of the clots also was exposed to intermittent ultrasound (1 MHz, 1.75 W/cm2) throughout the experiment. The ultrasound was delivered as a 2-second exposure followed by a 2-second rest interval. The overall difference in mean clot lysis between thrombi receiving ultrasound and those receiving no ultrasound was significant (p less than 0.001) at all concentrations of t-PA. For clots incubated with t-PA at a concentration of 300 IU/ml, ultrasound increased the percent lysis at 200 minutes from 42 +/- 5% (mean +/- SEM) to 64 +/- 10%. In six paired experiments in a rabbit jugular vein thrombosis model, rabbits received 1 mg t-PA alone or t-PA and intermittent ultrasound (1 MHz, 1.75 W/cm2) for 200 minutes. For rabbits receiving ultrasound and t-PA, lysis was 55 +/- 11% at 100 minutes compared with 30 +/- 12% for rabbits receiving only t-PA. Lysis was 6 +/- 10% for rabbits (n = 4) receiving ultrasound alone. No evidence for tissue damage was noted in rabbits exposed to intermittent ultrasound.
  
  
  CONCLUSIONS
  Exposure of whole blood clots in vitro to intermittent ultrasound combined with t-PA caused a significant enhancement of thrombolysis compared with t-PA alone. Intermittent ultrasound also showed a trend toward enhancement of t-PA-induced clot lysis in an animal thrombosis model. These data suggest that noninvasive intermittent ultrasound may be a useful adjunct to thrombolytic therapy.
authors.affiliation: Department of Hematology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
authors.forename: C G
authors.initials: CG
authors.lastname: Lauer
authors.forename: R
authors.initials: R
authors.lastname: Burge
authors.forename: D B
authors.initials: DB
authors.lastname: Tang
authors.forename: B G
authors.initials: BG
authors.lastname: Bass
authors.forename: E R
authors.initials: ER
authors.lastname: Gomez
authors.forename: B M
authors.initials: BM
authors.lastname: Alving
mesh_terms: D000818:Animals; D002021:Buffers; D004305:Dose-Response Relationship, Drug; D005342:Fibrinolysis / Q000187:drug effects / Q000528:radiation effects*; D010949:Plasma; D010958:Plasminogen / Q000494:pharmacology; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014465:Ultrasonics
chemical_list: D002021:Buffers; D010958:Plasminogen; D010959:Tissue Plasminogen Activator