title: There is synergism between high-intensity, low-frequency ultrasound and streptokinase but not with eptifibatide, heparin, and aspirin. Differential effects on fresh and aged blood clots. An in vitro study.
abstract: OBJECTIVE
  Ultrasound is emerging as a promising modality for recanalization of acutely thrombosed blood vessels, especially when associated with fibrinolytics. We assessed the efficacy of ultrasound combined with saline, heparin, eptifibatide, aspirin, and streptokinase in disruption of fresh as well as aged human blood clots, using an in vitro model.
  
  
  METHODS
  Blood clots from five donors, 2-4 or 48 hours old, were cut into 250-400 mg slices and immersed for 1, 15, or 30 min in 10 ml saline containing either heparin, eptifibatide, aspirin, streptokinase, or saline alone. Clots were then randomized to 10 s of 20 kHz ultrasound or immersion alone. After treatment, the percentage difference in weight was calculated.
  
  
  RESULTS
  Immersion of fresh clots without ultrasound in eptifibatide and heparin resulted in significantly more clot lysis than immersion in saline, aspirin, and streptokinase. Immersion of aged thrombi without ultrasound in heparin, eptifibatide, and aspirin had no additive effect over immersion in saline. Ultrasound enhanced clot disruption in all five solutions, in each immersion time and both in fresh and aged clots. Heparin and aspirin had no additive effect, compared with saline, on ultrasound disruption of both fresh and aged clots, whereas eptifibatide was less effective than saline. In contrast, streptokinase greatly enhanced disruption of both fresh (P=.004) and aged (P<.001) thrombi by ultrasound. The combinations of ultrasound with saline, heparin, eptifibatide, and aspirin were less effective on aged than fresh thrombi, whereas the combination of ultrasound with streptokinase was equally effective on fresh and aged thrombi.
  
  
  CONCLUSIONS
  Using a simple in vitro model, we found that the combination of streptokinase and low-frequency ultrasound had a synergistic effect on disruption of both fresh and aged blood clots. Further studies are needed to assess the role of heparin and antiplatelet agents in augmenting clot disruption by ultrasound in in vivo models of acute and subacute thrombosis.
authors.affiliation: Laboratory of Cardiovascular Biology, Felsenstein Research Institute, Rabin Medical Center, 49-100, Petah-Tiqwa, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Wyshelesky
authors.forename: Z
authors.initials: Z
authors.lastname: Iakobishvili
authors.forename: I
authors.initials: I
authors.lastname: Matz
authors.forename: G
authors.initials: G
authors.lastname: Golovchiner
authors.forename: M
authors.initials: M
authors.lastname: Vaturi
authors.forename: R J
authors.initials: RJ
authors.lastname: Siegel
authors.forename: Y
authors.initials: Y
authors.lastname: Birnbaum
mesh_terms: D001241:Aspirin / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D000077542:Eptifibatide; D005342:Fibrinolysis / Q000187:drug effects* / Q000528:radiation effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010455:Peptides / Q000494:pharmacology; D013300:Streptokinase / Q000494:pharmacology; D014465:Ultrasonics
chemical_list: D005343:Fibrinolytic Agents; D010455:Peptides; D006493:Heparin; D013300:Streptokinase; D000077542:Eptifibatide; D001241:Aspirin