The effects of streptokinase and hydroxyethyl starch on in vitro clot disruption by ultrasound

Background: In vitro studies showed that low-frequency ultrasound (US) caus es blood clot dissolution. This effect is augmented with thrombolytics, mic robubbles and microparticles. However, in animal models of transcutaneous d elivery, US alone is not effective, probably due to attenuation of US energ y by overlying skin. When combined with thrombolytics or microbubbles, tran scutaneous US is highly effective. Purpose: To assess the synergistic effec t of low-intensity low-frequency US and saline, hydroxyethyl starch (RAES) (a non-gas filled microparticle containing solution), streptokinase (STK), and their combination on blood clot disruption. Methods: Human blood clots from 4 healthy donors, 2-4 hours old, were immersed for 0, 15, or 30 min in 37 degreesC in 10 ml of the above-mentioned solutions, and then were rando mized to 10 see of 20 kHz US or no US. The % difference in weight was calcu lated. Results: Immersion for 30 min without US resulted in 13.8 +/- 1.2% c lot lysis in saline, and 22.0 +/- 1.3%, 21.7 +/- 2.1%, and 23.2 +/- 1.9% in STK, HAES, and STK + HAES, respectively (p = 0.002). US augmented clot lys is in all groups and at all time points. With low-intensity US, HAES was no t better than saline. Howe er, the combination of HAES + STK with US result ed in larger clot disruption at 15 see incubation time (46.7 +/- 3.2%) than with saline (29.6 +/- 2.1%), HAES (29.6 +/- 2.5%), and STK (32.8 +/- 3.6%) (p < 0.001). Conclusion: low-frequency, low-intensity US combined with HAE S and STK resulted in greater clot disruption at short incubation times. Th is combination may assist in achieving faster reperfusion in in vivo models .