Cavitational mechanisms in ultrasound-accelerated fibrinolysis.
The role of both inertial and stable cavitation was investigated during in vitro ultrasound-accelerated fibrinolysis by recombinant tissue plasminogen activator (rt-PA) in the presence and absence of Optison. A unique treatment configuration applied ultrasound, rt-PA and Optison to the interior of a plasma clot. Lysis efficacy was measured as clot weight reduction. Cavitational mechanisms were investigated by monitoring subharmonic and broadband noise. In the absence of Optison, 1.7 MHz pulsed ultrasound with 1.5 MPa peak-negative pressure applied for 30 min resulted in 45 +/- 19% lysis enhancement relative to rt-PA alone. Cavitation was not detected, indicating a role of noncavitational effects of ultrasound. The addition of Optison increased lysis enhancement to 88 +/- 25%. Inertial cavitation was present only at the start of the exposure, while low-amplitude subharmonic emissions persisted throughout. Additional protocols suggested a possible correlation between the increased lysis in the presence of Optison and the subharmonic emission, indicating a potentially important role of stable rather than inertial cavitation in microbubble-enhanced ultrasound-accelerated rt-PA-mediated thrombolysis.
Prokop
Adrian F
AF
Preclinical Research Department, EKOS Corporation, Bothell, Washington 98011, USA.
Soltani
Azita
A
Roy
Ronald A
RA
D000418:Albumins / Q000008:administration & dosage; D003287:Contrast Media / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D005466:Fluorocarbons / Q000008:administration & dosage; D006801:Humans; D045423:Microbubbles; D008863:Microspheres; D008955:Models, Cardiovascular; D011994:Recombinant Proteins / Q000008:administration & dosage; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000628:therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage; D014464:Ultrasonic Therapy / Q000379:methods*; D014465:Ultrasonics
D000418:Albumins; D003287:Contrast Media; C099458:FS 069; D005343:Fibrinolytic Agents; D005466:Fluorocarbons; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator