Ultrasound affects distribution of plasminogen and tissue-type plasminogen activator in whole blood clots in vitro.
Ultrasound of 2 MHz frequency and 1.2 W/cm(2) acoustic intensity was applied to examine the effect of sonication on recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis as well as on the distribution of plasminogen and t-PA within whole blood clots in vitro. Thrombolysis was evaluated quantitatively by measuring clot weight reduction and the level of fibrin degradation product D-dimer (FDP-DD) in the supernatant. Weight reduction in the group of clots treated both with ultrasound and rt-PA was 35.2% +/-6.9% which is significantly higher (p<0.0001) than in the group of clots treated with rt-PA only (19.9% +/-4.3%). FDP-DD level in the supernatants of the group treated with ultrasound and rt-PA increased sevenfold compared to the group treated with rt-PA alone, (14895 +/-2513 ng/ml vs. 2364 +/-725 ng/ml). Localization of fibrinolytic components within the clots was accomplished by using gel-entrapping technique and immunohistochemistry. Spatial distributions of t-PA and plasminogen showed clearly that ultrasound promoted the penetration of rt-PA into thrombi significantly (p<0.0001), and broadened the zone of lysis from 8.9 +/-2.6 microm to 21.2 +/-7.2 microm. We speculate that ultrasound enhances thrombolysis by affecting the distribution of rt-PA within the clot.
Devcic-Kuhar
Branka
B
Institute of General Physics, Vienna University of Technology, Austria.
Pfaffenberger
Stefan
S
Gherardini
Lisa
L
Mayer
Christoph
C
Gröschl
Martin
M
Kaun
Christoph
C
Benes
Ewald
E
Tschachler
Erwin
E
Huber
Kurt
K
Maurer
Gerald
G
Wojta
Johann
J
Gottsauner-Wolf
Michael
M
D005342:Fibrinolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence; D010958:Plasminogen / Q000032:analysis* / Q000378:metabolism; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000493:pharmacokinetics* / Q000528:radiation effects / Q000627:therapeutic use; D018084:Ultrasonography, Interventional / Q000379:methods*
D010958:Plasminogen; D010959:Tissue Plasminogen Activator