Thrombolytic enhancement with perfluorocarbon-exposed sonicated dextrose albumin microbubbles

Abstract

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.