Cavitational mechanisms in ultrasound-accelerated thrombolysis at 1 MHz.
Inertial cavitation is hypothesized to be a mechanism by which ultrasound (US) accelerates the dissolution of human blood clots when the clot is exposed to a thrombolytic agent such as tissue plasminogen activator (t-PA). To test this hypothesis, radiolabeled fibrin clots were exposed or sham-exposed in vitro to 1 MHz c.w. US in a rotating sample holder immersed in a water-filled tank at 37 degrees C. Percent clot dissolution after 60 min of US exposure was assessed by removing the samples, centrifuging, and measuring the radioactivity of the supernatant fluid relative to the pelletized material. To suppress acoustic cavitation, the exposure tank was contained within a hyperbaric chamber capable of pneumatic pressurization to 10 atmospheres (gauge). Various combinations of static pressure (0, 2, 5, and 7.5 atm gauge), US (0 or 4 W/cm(2) SATA), and t-PA (0 or 10 microg/mL) were employed, showing statistically significant reductions in thrombolytic activity as static pressure increased. To gain further insight, an active cavitation detection scheme was employed in which 1-micros duration tonebursts of 20-MHz US (< 1 kPa peak negative pressure, 1 Hz PRF) were used to interrogate clots subjected to US and static pressure. Results of this cavitation detection scheme showed that scattering from within the clot and broadband acoustic emissions that were both present during insonification were significantly reduced with application of static pressure. However, only about half of the acceleration of thrombolysis due to US could be removed by static pressure, suggesting the possibility of other mechanisms in addition to inertial cavitation.
Everbach
E C
EC
Department of Engineering, Swarthmore College, Swarthmore, PA 19081-1397, USA. ceverba1@swarthmore.edu
Francis
C W
CW
D006801:Humans; D066298:In Vitro Techniques; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014464:Ultrasonic Therapy / Q000379:methods*
D010959:Tissue Plasminogen Activator