Ultrasound has synergistic effects in vitro with tirofiban and heparin forthrombus dissolution

Previous studies have shown synergism between ultrasound and thrombolytic a gents or microbubbles on blood clot dissolution. It has not been investigat ed whether heparin or glycoprotein IIb/IIIa blockers enhance clot lysis by ultrasound. We compared the blood clot dissolution effect of saline, hepari n, tissue plasminogen activator (tPA), tirofiban, and an echocardiographic contrast media (Optison) without and with ultrasound application, Human blo od clots from four donors, 2 to 4 hours old, were cut into 200- to 400-mg s ections, weighed, and immersed for 2 minutes in 1 L of normal saline 0.9% s olution containing either heparin 1000 U, tirofiban 150 mu g, tPA 20 mg, Op tison 0.5 mL, or normal saline alone, Clots were randomized to 2 minutes ul trasound application or immersion alone without ultrasound. Ultrasound was applied with a 19.5 KHz catheter, After treatment, the clots were weighed, and the absolute and percent difference in weight was calculated. Immersion in hepa rin, tirofiban, and tPA without ultrasound did not augment clot di sruption relative to normal saline alone. Immersion in Optison (p=0.07) ten ded to result in less lysis than saline alone. Ultrasound enhanced clot dis solution compared to immersion alone with: saline (48.1+/-15.3% vs. 26.0+/- 13.8%, p<0.0000002); heparin (60.8+/-17.5% vs. 30.8+/-15.1%, p=0.000001); t irofiban (61.8+/-13.6% vs. 30.1+/-12.2%, p<0.0000001). tPA (53.1+/-15.3% vs . 30.2+/-11.5%, p<0.000002); and Optison (47.8+/-16.0% vs. 18.4+/-11.5%, p< 0.0000001). The combination of tirofiban with ultrasound, as well as hepari n with ultrasound, was associated with a significant augmentation of clot d issolution compared with the saline plus ultrasound group (p=0.002, 0.013, respectively). Ultrasound with tPA or with Optison had no significant augme ntation of clot dissolution over the ultrasound + saline effect. This in vi tro study of catheter-delivered high-intensity low-frequency ultrasound dem onstrates that: (1) tirofiban and heparin, as well as perfluorocarbon micro bubbles, augment clot dissolution by ultrasound; (2) augmentation of clot d issolution is evident even after only brief exposure of ultrasound and the drug studied. (C) 1999 Elsevier Science Ltd. All rights reserved.