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B. Devcic-Kuhar:
"Ultrasound Promotes Penetration of Thrombolytic Agent into Blood Clots and Enhances Thrombolysis";
Vortrag: 18th Int. Congress on Acoustics, Kyoto/J (eingeladen); 05.04.2004.

Today, enzymatic thrombolysis employing the fibrin-selective recombinant tissue plasminogen activator (rt-PA) is widely used in the clinical setting for treatment of myocardial infarction, cerebral insult and limb ischemia. However, penetration of rt-PA from the surrounding blood into the thrombus is a very slow process and a rate-limiting step in the reestablishment of blood flow and the maintenance of viability of the affected region, but it can be accelerated when taking place in an ultrasound field (sonothrombolysis). In our research on sonothrombolysis we have studied the effects of therapeutic ultrasound on thrombolysis enhancement in vitro. Clot weight loss measurements and measurements of concentration of the fibrin degradation product D-dimer in the supernatant showed that ultrasound of 2 MHz frequency and 1.2 W/cm2 acoustic intensity enforced thrombolysis significantly. By using gel immobilization technique and immuno-histochemistry, we were able to localize plasminogen and rt-PA within the clot. The spatial distributions of these fibrinolytic components showed clearly that ultrasound promoted the penetration of rt-PA into thrombi significantly and broadened the zone of lysis from 9 µm to 21 µm on average. We have shown for the first time that ultrasound facilitates the access of rt-PA to the deeper layers of the clot, thus leading to significantly faster clot dissolution.