Effect of externally applied focused acoustic energy on clot disruption in vitro.

Application of low-frequency ultrasound for clot disruption has been suggested as a potential therapy to enhance thrombus dissolution, but the optimal mode for delivery of ultrasound with clot-disruptive properties has not yet been extensively explored. Target-specific effects are desirable and may be accomplished by focusing the ultrasound. Adequate focusing, however, requires a short wavelength. The aim of this study was to compare the clot-disruptive effects of different modalities of focused acoustic energy. An in vitro model (10 blood clots for each modality) was used to test the clot-disruptive capacity of (i) shock waves generated in an electrohydraulic lithotriptor; (ii) focused continuous ultrasound offrequency 1.1 MHz, delivered from a specially constructed piezoelectric transducer; and (iii) focused pulse-modulated ultrasound of frequency 1.1 MHz delivered from the same transducer. Exposure to 30s of focused pulse-modulated ultrasound caused a marked reduction (99±2%) in clot weight compared with 30 shock waves (11 ± 5%) or 30 s exposure to focused continuous wave ultrasound (I ±6%) (P < 0.0001). The observed marked and rapid disruptive effect on blood clots of focused high-frequency ultrasound indicates an alternative approach for external ultrasound-mediated thrombus destruction in vivo. The focused pulse-modulated technique has potential to exhibit the desired effect in a well-defined target volume and provides the means for control of the average power.

[1]  R S Meltzer,et al.  Ultrasound accelerates urokinase-induced thrombolysis and reperfusion. , 1994, American heart journal.

[2]  C. Francis,et al.  Characterization of ultrasound-potentiated fibrinolysis in vitro , 1993 .

[3]  A. Kinn,et al.  Implications of cavitation phenomena for shot intervals in extracorporeal shock wave lithotripsy. , 1995, British journal of urology.

[4]  M. Fishbein,et al.  Ultrasonic clot disruption: an in vitro study. , 1990, American heart journal.

[5]  G Trübestein,et al.  Thrombolysis by ultrasound. , 1976, Clinical science and molecular medicine. Supplement.

[6]  C G Lauer,et al.  Effect of Ultrasound on Tissue‐Type Plasminogen Activator‐Induced Thrombolysis , 1992, Circulation.

[7]  K. Tachibana,et al.  Enhancement of fibrinolysis with ultrasound energy. , 1992, Journal of vascular and interventional radiology : JVIR.

[8]  P. T. Onundarson,et al.  Enhancement of fibrinolysis in vitro by ultrasound. , 1992, The Journal of clinical investigation.

[10]  F. Van de Werf,et al.  Intravenous tissue plasminogen activator and size of infarct, left ventricular function, and survival in acute myocardial infarction. , 1988, BMJ.

[11]  L. Crum,et al.  Acoustic Cavitation , 1982 .

[12]  M. Fishbein,et al.  High intensity, low frequency catheter-delivered ultrasound dissolution of occlusive coronary artery thrombi: an in vitro and in vivo study. , 1994, Journal of the American College of Cardiology.

[13]  U. Rosenschein,et al.  Analysis of coronary ultrasound thrombolysis endpoints in acute myocardial infarction (ACUTE trial). Results of the feasibility phase. , 1997, Circulation.

[14]  D. Kremer,et al.  Effects of ultrasound energy on thrombi in vitro. , 1993, Catheterization and cardiovascular diagnosis.

[15]  J. Bernheim,et al.  Experimental ultrasonic angioplasty: disruption of atherosclerotic plaques and thrombi in vitro and arterial recanalization in vivo. , 1990, Journal of the American College of Cardiology.

[16]  Z. Vered,et al.  Does external ultrasound accelerate thrombolysis? Results from a rabbit model. , 1994, Circulation.

[17]  J. Forrester New standard for success of thrombolytic therapy. An earnest proposal. , 1995, Circulation.

[18]  S. Olsson,et al.  Enhancement of thrombolysis by ultrasound. , 1994, Ultrasound in medicine & biology.

[19]  M. A. Margulis,et al.  Sonochemistry and cavitation , 1995 .

[20]  K. Kuck,et al.  Coronary ultrasound thrombolysis in a patient with acute myocardial infarction , 1994, The Lancet.

[21]  H. White,et al.  Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. , 1987, The New England journal of medicine.

[22]  S. Laniado,et al.  Study of the mechanism of ultrasound angioplasty from human thrombi and bovine aorta. , 1994, The American journal of cardiology.

[23]  C. Francis,et al.  Ultrasound enhancement of thrombolysis and reperfusion in vitro. , 1993, Journal of the American College of Cardiology.

[24]  M. Fishbein,et al.  Transcutaneous ultrasound augments lysis of arterial thrombi in vivo. , 1996, Circulation.

[25]  Eric J. Topol,et al.  Illusion of Reperfusion Does Anyone Achieve Optimal Reperfusion During Acute Myocardial Infarction? , 1993, Circulation.

[26]  A. M. Skene,et al.  TRIAL OF TISSUE PLASMINOGEN ACTIVATOR FOR MORTALITY REDUCTION IN ACUTE MYOCARDIAL INFARCTION Anglo-Scandinavian Study of Early Thrombolysis (ASSET) , 1988, The Lancet.

[27]  M. Fishbein,et al.  Dissolution of Peripheral Arterial Thrombi by Ultrasound , 1991, Circulation.