Enhancement of enzymatic fibrinolysis with 2-MHz ultrasound and microbubbles.
BACKGROUND
Microbubbles used for echo-contrast agents accelerate enzymatic fibrinolysis of clots exposed to low-frequency ultrasound (US). It is not known whether microbubbles are also effective in enhancing high-frequency US-driven enzymatic fibrinolysis.


RESULTS
Calibrated whole blood clots were exposed to US, or US and galactose-based microbubbles (Levovist), with or without recombinant tissue plasminogen activator (rt-PA) in an in-vitro flow system. We used low-intensity, 2-MHz, pulsed wave US. Relative weight reduction of clot +/- SD was 30.7 +/- 9.5% after exposure to microbubbles, rt-PA and US, 13.1 +/- 2.6% after exposure to rt-PA and US, 10.9 +/- 3.6% after exposure to microbubbles and US, and 6.1 +/- 1.9% after exposure to US alone. anova demonstrated a significant effect of rt-PA (P =0.001), microbubbles (P = 0.012), and interaction of both (P = 0.022).


CONCLUSIONS
The application of galactose-based microbubbles (Levovist) strongly accelerates lysis of clots exposed to 2 MHz, low-intensity US in vitro both with and without rt-PA. The findings suggest a synergy between microbubbles and rt-PA. These methods routinely used for transcranial diagnostic applications have the potential to improve the efficacy of intravenous rt-PA in acute ischemic stroke.
Cintas
P
P
Departments of Neurology and Hematology, EA2049, University of Toulouse, Toulouse, France.
Nguyen
F
F
Boneu
B
B
Larrue
V
V
D001777:Blood Coagulation / Q000187:drug effects / Q000528:radiation effects; D003287:Contrast Media; D057487:Enzyme Therapy; D005342:Fibrinolysis / Q000528:radiation effects*; D005690:Galactose; D006801:Humans; D045423:Microbubbles; D008955:Models, Cardiovascular; D020521:Stroke / Q000628:therapy; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000494:pharmacology* / Q000627:therapeutic use; D014464:Ultrasonic Therapy / Q000379:methods*
D003287:Contrast Media; D010959:Tissue Plasminogen Activator; D005690:Galactose