Ultrasound-enhanced thrombolysis at 20 kHz with air-filled and perfluorocarbon-filled contrast bispheres

Background: Ultrasound (US) at low frequencies has been shown to enhance clot lysis by itself and in the presence of urokinase (UK). The comparative effects of air-filled versus perfluorocarbon-filled polymer bispheres in enhancing this effect have not been previously demonstrated. Methods: Freshly drawn human blood was incubated at 37 degreesC for 2 hours, and the subsequent formed clot was dried and weighed. It was then exposed to saline control, saline + UK (10,000 IU), saline + UK + US, saline + UK + US + low shell-strength polymer bispheres (PB1), saline + UK + US + high shell-strength polymer bispheres (PB2), and perfluorocarbon-filled high shell-strength polymer bipsheres (PB3) for a total of 6 minutes. Clots were removed and weighed to determine the percentage of thrombolysis. Results: The percentage of clot lysis for each study group was as follows: saline 18.5% +/- 4%, US alone 22.2% +/- 5%, UK alone 21.9% +/- 4%, US+UK 32.2% +/- 8% (P < .05 compared with UK alone), US+UK+PB1 36.9% 8%, US+UK+PB2 34.3% +/- 8%, and US+UK+PB3 45.0% +/-: 11% (P < .05 compared with US+UK, P < .05 compared with US+UK+PB2). Conclusion: Ultrasound at 20 kHz significantly enhances clot lysis. The addition of perfluorocarbon-filled bispheres increased this effect more significantly than did the addition of air-filled polymer bispheres.