Acceleration of fibrinolysis by high-frequency ultrasound: The contribution of acoustic streaming and temperature rise

High-frequency ultrasound has been shown to accelerate enzymatic fibrinolys is. One of the supposed mechanisms of this effect is the enhancement of mas s transport by acoustic streaming, i.e., ultra sound-induced macroscopic fl ow around the clot. In this study, which is aimed at further elucidating th e mechanisms of the acceleration of fibrinolysis by ultrasound, we investig ated whether ultrasound would accelerate fibrinolysis if the flow around th e thrombus is already present, as may occur in vivo. The effect of the ultr asound-induced temperature rise was also studied. In a model of a plasma cl ot submerged in plasma, containing tissue-type plasminogen activator, mild stirring of the outer plasma producing a shear rate of 40 seconds(-1) at th e surface of the clot resulted in a two-fold acceleration of lysis. A simil ar effect was obtained with ultrasound (1 MHz, 2 W/cm(2)). Furthermore, if ultrasound was applied together with stirring, only 30% acceleration by ult rasound was documented, fully attributable to the concomitant temperature r ise. In a model with tissue-type plasminogen activator incorporated through out a plasma clot, the effect of ultrasound (two-fold shortening of lysis t ime) was fully attributable to the concomitant temperature rise of a few de grees. We concluded that the acceleration of enzymatic plasma clot lysis by high-frequency ultrasound in the models we used can be largely explained b y a combination of the effects of heating and acoustic streaming, equivalen t to mild stirring. The thermal effects can hardly be utilized in vivo due to the danger of tissue overheat. The therapeutic advantage of transcutaneo us high-frequency ultrasound as an adjunct to thrombolytic therapy may appe ar limited to the situations where there is no flow in the direct environme nt of the thrombus. (C) 2000 Elsevier Science Ltd. All rights reserved.