Ultrasound accelerates urokinase-induced thrombolysis and reperfusion

We have shown that ultrasound accelerates TPA-induced thrombolysis in vitro as assessed by release of labeled fibrinogen from radioactive labeled clots. Others have shown that ultrasound shortens the time to recanalization of TPA treated thrombi in animal models. The aim of this study was to test the hypothesis that ultrasound enhances thrombolysis and reperfusion by using urokinase in an in vitro flow system. An in vitro flow system of a branching tubing circuit was developed. Flow in one branch was obstructed by a thrombus. Five control clots were exposed to continuous wave ultrasound at a frequency of 1 MHz and intensity of 2.5 W/cm2 only without any thrombolytic agent (group 1). Twenty clots were exposed to a bolus of 80,000 U of urokinase and randomized to either ultrasound exposure (group 2) or to urokinase only without ultrasound (group 3). Flow distal to the clot and the rate of release of radiolabeled fibrin were used as indexes of reperfusion and thrombolysis, respectively. Exposure to ultrasound significantly accelerated urokinase-mediated reperfusion, with 40.6% +/- 11.8% of maximal flow in group 2 versus 1.3% +/- 0.7% in group 3, p < 0.0015 after 25 min. The maximal difference in flow between groups 2 and 3 was achieved at 40 minutes (67.4% +/- 11.1% vs 13.1% +/- 5.6%, p < 0.0009). Thrombolysis was significantly higher after 25 minutes of ultrasound exposure (24.1% +/- 4.6% in the ultrasound-treated group vs 9.7% +/- 3.5% in group 3, p < 0.013). The maximal difference in thrombolysis between groups 2 and 3 was 60 minutes. (52.5% +/- 5.1% vs 18.7% +/- 6.2%, p < 0.00015).(ABSTRACT TRUNCATED AT 250 WORDS)