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Characterization of ultrasound-potentiated fibrinolysis in vitro
A Blinc, CW Francis, JL Trudnowski and EL Carstensen
Department of Medicine, University of Rochester School of Medicine and
Dentistry, NY.
We have characterized the effects of ultrasound on fibrinolysis in vitro to
investigate the mechanism of ultrasonic potentiation of fibrinolysis and to
identify potentially useful ultrasound parameters for therapeutic
application. Radiolabeled clots in thin walled tubes were exposed to
ultrasound fields in a water bath at 37 degrees C, and lysis was measured
by solubilization of radiolabel. Ultrasound accelerated lysis of plasma,
whole blood, and purified fibrin clots mediated by recombinant tissue-type
plasminogen activator (rt-PA), urokinase, or streptokinase, but ultrasound
by itself caused no clot solubilization. The degree of ultrasonic
potentiation was dependent on plasminogen activator concentration,
increasing from 2.2-fold at a streptokinase concentration of 75 U/mL to
5.5-fold at 250 U/mL in a 1 MHz ultrasound field at 4 W/cm2. Ultrasound
exposure resulted in heating due to absorption by the plastic tube, but the
temperature increase was insufficient to account for the increase in clot
lysis rate, indicating that the primary effect was nonthermal. Ultrasound
did not accelerate hydrolysis of a peptide substrate by rt-PA and did not
alter the rate of plasmic degradation of fibrinogen, indicating that the
augmentation of enzymatic fibrinolysis required the presence of a fibrin
gel. The acceleration of fibrinolysis by ultrasound was greater at higher
intensities and duty cycles and was maximum at frequencies between 1 and
2.2 MHz, but decreased at 3.4 MHz. These findings suggest that ultrasound
accelerates enzymatic fibrinolysis by increasing transport of reactants
through a cavitation-related mechanism.
Volume 81,
Issue 10,
pp. 2636-2643,
05/15/1993
Copyright © 1993 by The American Society of Hematology
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