title: Low-frequency ultrasound induces nonenzymatic thrombolysis in vitro.
abstract: OBJECTIVE
  To evaluate whether ultrasound, applied over a distance of several centimeters and in the absence of thrombolytic agents, may have a thrombolytic effect on blood clots.
  
  
  METHODS
  Low-frequency (20 kHz) continuous wave ultrasound at different intensity levels (0.15-1.2 W/cm2) and exposure times (5, 10, and 20 minutes) was assessed for its potential to induce thrombolysis of fresh human blood clots. The ultrasound effect was also studied in combination with recombinant tissue-type plasminogen activator-mediated thrombolysis. Experiments were carried out in a flow model in degassed sodium phosphate buffer at 37 degrees C at a distance of 3 cm from the ultrasonic probe to the blood clots. Regardless of ultrasound exposure times, blood clots in all experimental groups and the control group were left in the flow system for 20 minutes.
  
  
  RESULTS
  The use of ultrasound alone showed a significant thrombolytic effect compared with the control group, with a statistically significant effect at 0.15 W/cm2 and exposure of 10 minutes (P = .02). There was a clear correlation between the extent of weight loss and the chosen intensity level and exposure time. Complete disruption in 8 of 10 blood clots occurred at 1.2 W/cm2 within 10 min. Addition of ultrasound to recombinant tissue-type plasminogen activator-mediated thrombolysis significantly enhanced thrombolysis compared with application of recombinant tissue-type plasminogen activator or ultrasound alone (P = .0001), with the results pointing toward a purely additive, nonsynergistic effect of the 2 treatment modalities. Lysis was more effective in fresh thrombi.
  
  
  CONCLUSIONS
  The use of low-frequency ultrasound alone, without addition of a thrombolytic drug, has the potential to induce thrombolysis over a distance. Combination of ultrasound with recombinant tissue-type plasminogen activator is superior to either treatment alone. Ultrasound is a promising tool for developing an alternative or additional treatment modality for acute cerebral vessel occlusion.
authors.affiliation: Department of Neurology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Nedelmann
authors.forename: B Martin
authors.initials: BM
authors.lastname: Eicke
authors.forename: Ernst G
authors.initials: EG
authors.lastname: Lierke
authors.forename: Axel
authors.initials: A
authors.lastname: Heimann
authors.forename: Oliver
authors.initials: O
authors.lastname: Kempski
authors.forename: Hanns C
authors.initials: HC
authors.lastname: Hopf
mesh_terms: D006801:Humans; D011994:Recombinant Proteins / Q000627:therapeutic use; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D014464:Ultrasonic Therapy
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator