Ultrasound Promotes Penetration of Thrombolytic Agent into Blood Clots and Enhances Thrombolysis
Branka Devcic-Kuhar, *Stefan Pfaffenberger, Lisa Gherardini, Martin Grschl, Ewald Benes, *Johann Wojta, *Michael Gottsauner-Wolf Institute of General Physics, Vienna University of Technology, Austria
devcic@iap.tuwien.ac.at
*
Department of Cardiology, Clinic for Inner Medicine II, Vienna University, Austria Abstract
plasminogen activator (rt-PA) which is a genetically engineered copy of the human's own tissue-type plasminogen activator (t-PA) [1]. If the pressure drop across the clot is negligible, the penetration of rt-PA from the surrounding liquid into the thrombus is based solely on diffusion. A narrow lysis front, not exceeding 5-8 m in depth, moves slowly inwards and fibrin degradation proceeds layer by layer [2]. In addition to enzymatic thrombolysis, the possibility of lysing blood clots by directly applying intravascular ultrasound has long been known. The thrombolytic effect of low frequency ultrasound (20 to 50 kHz) at high intensities (up to 20 W/cm2) is primarily based on mechanical disruption and disintegration of blood clots. In contrast, exposure to higher ultrasound frequencies (1 to 3 MHz) at moderate intensities (up to 4 W/cm2) in conjunction with pharmacologic therapy is not associated with mechanical alterations of the clots, but with enhanced enzymatic activity of the thrombolytic agents. Consequently, numerous studies [3-8] have focussed recently on the investigation of non-invasive ultrasound as a safer and cheaper alternative to catheter based, invasive ultrasound, also requiring less technical and logistical factors for clinical implementation. It has been assumed that ultrasound exerts its beneficial effects on thrombolysis by promoting the transport of enzymes into clots and by increasing the uptake of rtPA [9]. However, to date – at least to our knowledge – no data are available on the distribution and the localization of fibrinolytic enzymes in blood clots during ultrasound treatment. Therefore, in this study we tested the hypothesis whether ultrasound changes the distribution and localization of fibrinolytic enzymes within the blood clot and on the clot surface and thus supports enzymatic thrombolysis by rt-PA.

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