Circulation, Vol 86, 1257-1264, Copyright © 1992 by American Heart Association
CG Lauer, R Burge, DB Tang, BG Bass, ER Gomez and BM Alving
BACKGROUND. The efficacy of fibrinolytic therapy is limited by the small
surface area of the clot that is available for the binding of the
thrombolytic agent, such as tissue-type plasminogen activator (t-PA). We
hypothesized that exposure of the clot to ultrasound during thrombolytic
treatment could enhance lysis through perturbation of the thrombus, which
would expose additional fibrin binding sites for t-PA. METHODS AND RESULTS.
Whole human blood clots containing radiolabeled fibrinogen were incubated
in vitro for 200 minutes with Tris-albumin buffer containing t-PA at
concentrations ranging from 3 to 3,000 IU/ml. In paired experiments, one of
the clots also was exposed to intermittent ultrasound (1 MHz, 1.75 W/cm2)
throughout the experiment. The ultrasound was delivered as a 2-second
exposure followed by a 2- second rest interval. The overall difference in
mean clot lysis between thrombi receiving ultrasound and those receiving no
ultrasound was significant (p less than 0.001) at all concentrations of
t-PA. For clots incubated with t-PA at a concentration of 300 IU/ml,
ultrasound increased the percent lysis at 200 minutes from 42 +/- 5% (mean
+/- SEM) to 64 +/- 10%. In six paired experiments in a rabbit jugular vein
thrombosis model, rabbits received 1 mg t-PA alone or t-PA and intermittent
ultrasound (1 MHz, 1.75 W/cm2) for 200 minutes. For rabbits receiving
ultrasound and t-PA, lysis was 55 +/- 11% at 100 minutes compared with 30
+/- 12% for rabbits receiving only t-PA. Lysis was 6 +/- 10% for rabbits (n
= 4) receiving ultrasound alone. No evidence for tissue damage was noted in
rabbits exposed to intermittent ultrasound. CONCLUSIONS. Exposure of whole
blood clots in vitro to intermittent ultrasound combined with t-PA caused a
significant enhancement of thrombolysis compared with t-PA alone.
Intermittent ultrasound also showed a trend toward enhancement of
t-PA-induced clot lysis in an animal thrombosis model. These data suggest
that noninvasive intermittent ultrasound may be a useful adjunct to
thrombolytic therapy.
ARTICLES
Effect of ultrasound on tissue-type plasminogen activator-induced thrombolysis
Department of Hematology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
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