Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model.

Journal article

INTRODUCTION: Thrombolytics such as recombinant tissue plasminogen activator (rt-PA) have advanced the treatment of ischemic stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism. OBJECTIVE: To improve the efficacy of this thrombolytic therapy, the synergistic effect of rt-PA and 120 kHz or 1.0 MHz ultrasound was assessed in vitro using a porcine clot model. MATERIALS AND METHODS: Fully retracted whole blood clots prepared from fresh porcine blood were employed to compare rt-PA thrombolytic treatment with and without exposure to 120-kHz or 1-MHz ultrasound. For sham studies (without ultrasound), clot mass loss was measured as a function of rt-PA concentration from 0.003 to 0.107 mg/ml. For combined ultrasound and rt-PA treatments, peak-to-peak pressure amplitudes of 0.35, 0.70 or 1.0 MPa were employed. The range of duty cycles varied from 10% to 100% (continuous wave) and the pulse repetition frequency was fixed at 1.7 KHz. RESULTS: For rt-PA alone, the mass loss increased monotonically as a function of rt-PA concentration up to approximately 0.050 mg/ml. With ultrasound and rt-PA exposure, clot mass loss increased by as much as 104% over rt-PA alone. Ultrasound without the presence of rt-PA did not significantly enhance thrombolysis compared to control treatment. The ultrasound-mediated clot mass loss enhancement increased with the square root of the overall treatment duration. CONCLUSIONS: Both 120-kHz and 1-MHz pulsed and CW ultrasound enhanced rt-PA thrombolysis in a porcine whole blood clot model in vitro. No clear dependence of the observed thrombolytic enhancement on ultrasound duty cycle was evident. The lack of duty cycle dependence suggests a more complex mechanism that could not be sustained by merely increasing the pulse duration.

Authors: Holland, C; Vaidya, S; Datta, S; Coussios, C; Shaw, G

• Publication status: Published
• Journal: Thrombosis research
• Volume: 121
• Issue: 5
• Pages: 663-673
• Publication date: 2008-01-01
• DOI: 10.1016/j.thromres.2007.07.006
• EISSN: 1879-2472
• ISSN: 0049-3848
• Language: English
• Keywords: Animals; Recombinant Proteins; Thrombolytic Therapy; Ultrasonic Therapy; Tissue Plasminogen Activator; Swine