title: Synergism of aspirin and heparin with a low-frequency non-invasive ultrasound system for augmentation of in-vitro clot lysis.
abstract: BACKGROUND
  Aspirin, glycoprotein IIb/IIIa inhibitors and heparin are routinely used in acute coronary syndromes. Previously we showed that there is synergism between ultrasound and heparin and tirofiban in augmenting blood clot disruption. However, there is a little data on a possible synergism of low-frequency ultrasound with aspirin for in-vitro clot dissolution, and especially on the combination of aspirin with heparin and/or glycoprotein IIb/IIIa inhibitors.
  
  
  METHODS
  Human blood clots (n = 320) were incubated for 10 or 20 minutes in saline containing aspirin alone or combined with heparin and/or tirofiban and/or eptifibatide. Clots were randomly treated with low-frequency ultrasound (27.3 kHz) or incubation only. The percent clot weight loss and the incremental effect of ultrasound were calculated.
  
  
  RESULTS
  The most significant incremental effect of ultrasound on clot weight reduction was detected with aspirin alone (5.2 +/- 2.3% and 5.2 +/- 2.6% after 10' and 20', p = 0.04 and p = 0.06, respectively) and in combination with heparin (8.8 +/- 2.5% and 11.5 +/- 2.7% after 10' and 20', p = 0.01 and p = 0.0001, respectively). The greatest absolute magnitude of clot weight reduction was observed with ultrasound combined with aspirin and heparin (48.5 +/- 9.5% after 20'). The addition of tirofiban or eptifibatide to aspirin, heparin and ultrasound did not increase clot lysis. However, eptifibatide had significantly better synergism than tirofiban (p = 0.025 and p = 0.015, after 10 and 20 minutes, respectively).
  
  
  CONCLUSIONS
  Aspirin alone or in combination with heparin results in significant augmentation of clot lysis and is synergistic with application of low-frequency ultrasound for 10 and 20 minutes only. These results may have important implications for a possible use of low-frequency ultrasound in treatment algorithms of acute coronary syndromes.
authors.affiliation: Division of Cardiology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
authors.forename: Shaul
authors.initials: S
authors.lastname: Atar
authors.forename: Yoram
authors.initials: Y
authors.lastname: Neuman
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Yochai
authors.initials: Y
authors.lastname: Birnbaum
authors.forename: Huai
authors.initials: H
authors.lastname: Luo
authors.forename: Sergio
authors.initials: S
authors.lastname: Kobal
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Siegel
mesh_terms: D000328:Adult; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D006493:Heparin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D015912:Thrombolytic Therapy / Q000379:methods*; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D006493:Heparin; D000077466:Tirofiban; D000077542:Eptifibatide; D001241:Aspirin