Ultrasound assisted clot lysis for stroke therapy

• Published in: The Journal of the Acoustical Society of America 2001-05, Vol.109 (5_Supplement), p.2456-2457
• Main Authors: Shaw, George J., Hahn, Nancy L., Wagner, Kenneth R., Kanter, Daniel S., Holland, Christy K.
• Format: Article
• Language: English
• ISSN: 0001-4966; 1520-8524
• DOI: 10.1121/1.4744712

Thrombolytics such as tissue plasminogen activator (tPA) have advanced the treatment of ischemic stroke. To aid in the development of a transcranial ultrasound thrombolysis system (TUTS), the synergistic thrombolytic effect of tissue plasminogen activator (tPA) and 1-MHz ultrasound was assessed in vitro in a porcine clot model. Thirty clots were made by incubating 2-ml aliquots of citrated whole pig blood with 2 μl of bovine thrombin (1 NIH Unit/μl) at 37 °C for 3 h, refrigerated overnight, blotted, and weighed. Clots were placed in an acoustically transparent latex sample holder filled with porcine fresh frozen plasma and tPA at a clinically relevant concentration of 0.0126 mg/ml. The clots were either sham exposed to ultrasound (0.0-atm amplitude) or exposed to 1-MHz pulsed ultrasound over a range of duty cycles (10%–100%) at two amplitudes (1.9 and 11.4 atm) for 30 min in a 37 °C water bath, and were weighed to determine the efficacy of thrombolysis. Clots that received continuous wave ultrasound treatment exhibited significantly more thrombolysis than those that were sham exposed (p=0.001, students t-test). The TUTS technology promises to improve the effectiveness of thrombolytic drugs so that ultimately lower concentrations of drugs can be used for faster recanalization of blocked arteries. [Work supported by The Neuroscience Institute, University of Cincinnati Medical Center.]