Thrombolytic Enhancement with Perfluorocarbon-exposed Sonicated Dextrose Albumin Microbubbles

Whereas low-intensity, high-frequency ultrasound (US) alone appears to cause minimal thrombolysis, US combined with air-filled microbubbles does increase the amount of urokinase (UK)-mediated clot lysis (CL). Because this phenomenon may be mediated by cavitation-induced streaming, we hypothesized that perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles, which are more stable than air-filled microbubbles, may also enhance US-induced thrombolysis. We measured the percentage CL of equally sized thrombi (1.0 +/- 0.1 mg) made from freshly drawn blood incubated for 2 hours and then exposed to 20 kHz US (0.846 MPa peak negative pressure). The thrombi were bathed in 4 ml of saline solution, UK alone (20,000 U), PESDA alone, or a combination of PESDA with UK. The percentage CL achieved with PESDA and therapeutic US was also compared with the percentage CL achieved with room air-filled sonicated dextrose albumin (RASDA) microbubbles. When compared with US alone (24% +/- 13% CL) or UK alone (17% +/- 3% CL), PESDA plus US produced significantly better CL (43% +/- 17%; p< 0.05). PESDA combined with US also produced significantly greater CL than RASDA combined with US (28% +/- 9%; p < 0.05). The optimal CL was achieved with a combination of PESDA with UK with US (60% +/- 14% CL). We conclude that PESDA microbubbles alone may be capable of inducing thrombolysis when insonified with a low-frequency transducer.