Catheter-delivered ultrasound potentiates in vitro thrombolysis

PURPOSE: To develop a catheter-directed method to enhance urokinase-mediated thrombolysis with use of ultrasound. MATERIALS AND METHODS: A prototype catheter was constructed by using a 9-F piezoelectric crystal capable of producing 640-kHz pulsed ultrasound energy. Clots formed in vitro from whole blood were trace-labeled with iodine-125 fibrinogen, and the release of radiolabeled fibrin degradation products was measured in the presence of urokinase, ultrasound, or a combination of urokinase and ultrasound. RESULTS: By 30 minutes, clot lysis was more complete with urokinase plus ultrasound (78.7% +/- 5.3 [mean +/- SD]) than with ultrasound alone (19.3% +/- 10.0) or urokinase alone (47.9% +/- 10.0) (P <.001 for ultrasound and urokinase vs either alone), The time to 50% clot lysis was shortened by 46% on average with the application of urokinase and ultrasound compared with urokinase alone (P <.03). CONCLUSIONS: Catheter-based ultrasound enhances enzymatic thrombolysis in vitro and may be a practical means to reduce the dose of enzyme and the time needed to achieve clot lysis in vivo.