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© 2002 by the American Institute of Ultrasound in Medicine
J Ultrasound Med 21:649-656 • 0278-4297

Low-Frequency Ultrasound Induces Nonenzymatic Thrombolysis In Vitro

Max Nedelmann, MD, B. Martin Eicke, MD, Ernst G. Lierke, PhD, Axel Heimann, DVM, Oliver Kempski, MD and Hanns C. Hopf, MD

Department of Neurology (M.N., B.M.E., E.G.L., H.C.H.) and Institute for Neurosurgical Pathophysiology (A.H., O.K.), Johannes Gutenberg University, Mainz, Germany.

Address correspondence and reprint requests to Max Nedelmann, MD, Department of Neurology, Johannes Gutenberg University, Langenbeckstrasse 1, 55101 Mainz, Germany.

Objective. To evaluate whether ultrasound, applied over a distance of several centimeters and in the absence of thrombolytic agents, may have a thrombolytic effect on blood clots. Methods. Lowfrequency (20 kHz) continuous wave ultrasound at different intensity levels (0.15–1.2 W/cm2) and exposure times (5, 10, and 20 minutes) was assessed for its potential to induce thrombolysis of fresh human blood clots. The ultrasound effect was also studied in combination with recombinant tissue-type plasminogen activator–mediated thrombolysis. Experiments were carried out in a flow model in degassed sodium phosphate buffer at 37°C at a distance of 3 cm from the ultrasonic probe to the blood clots. Regardless of ultrasound exposure times, blood clots in all experimental groups and the control group were left in the flow system for 20 minutes. Results. The use of ultrasound alone showed a significant thrombolytic effect compared with the control group, with a statistically significant effect at 0.15 W/cm2 and exposure of 10 minutes (P = .02). There was a clear correlation between the extent of weight loss and the chosen intensity level and exposure time. Complete disruption in 8 of 10 blood clots occurred at 1.2 W/cm2 within 10 min. Addition of ultrasound to recombinant tissue-type plasminogen activator–mediated thrombolysis significantly enhanced thrombolysis compared with application of recombinant tissue-type plasminogen activator or ultrasound alone (P = .0001), with the results pointing toward a purely additive, nonsynergistic effect of the 2 treatment modalities. Lysis was more effective in fresh thrombi. Conclusions. The use of low-frequency ultrasound alone, without addition of a thrombolytic drug, has the potential to induce thrombolysis over a distance. Combination of ultrasound with recombinant tissue-type plasminogen activator is superior to either treatment alone. Ultrasound is a promising tool for developing an alternative or additional treatment modality for acute cerebral vessel occlusion.

Abbreviations: rt-PA, recombinant tissue-type plasminogen activator

Key Words: ultrasound • thrombolysis • fibrinolysis • tissue-type plasminogen activator • stroke




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Copyright © 2002 by the American Institute of Ultrasound in Medicine.