High-frequency ultrasound has been shown to accelerate enzymatic fibrinolysis. One of the supposed mechanisms of this effect is the enhancement of mass transport by acoustic streaming, i.e., ultrasound-induced macroscopic flow around the clot. In this study, which is aimed at further elucidating the mechanisms of the acceleration of fibrinolysis by ultrasound, we investigated whether ultrasound would accelerate fibrinolysis if the flow around the thrombus is already present, as may occur in vivo. The effect of the ultrasound-induced temperature rise was also studied. In a model of a plasma clot submerged in plasma, containing tissue-type plasminogen activator, mild stirring of the outer plasma producing a shear rate of 40 seconds(-1) at the surface of the clot resulted in a two-fold acceleration of lysis. A similar effect was obtained with ultrasound (1 MHz, 2 W/cm(2)). Furthermore, if ultrasound was applied together with stirring, only 30% acceleration by ultrasound was documented, fully attributable to the concomitant temperature rise. In a model with tissue-type plasminogen activator incorporated throughout a plasma clot, the effect of ultrasound (two-fold shortening of lysis time) was fully attributable to the concomitant temperature rise of a few degrees. We concluded that the acceleration of enzymatic plasma clot lysis by high-frequency ultrasound in the models we used can be largely explained by a combination of the effects of heating and acoustic streaming, equivalent to mild stirring. The thermal effects can hardly be utilized in vivo due to the danger of tissue overheat. The therapeutic advantage of transcutaneous high-frequency ultrasound as an adjunct to thrombolytic therapy may appear limited to the situations where there is no flow in the direct environment of the thrombus.
