Augmentation of in-stent clot dissolution by low frequency ultrasound combined with aspirin and heparin. An ex-vivo canine shunt study

Introduction: Ultrasound can accelerate clot dissolution in vitro and in vivo. We used an ex vivo canine shunt to investigate low frequency ultrasound effects on platelet-rich stent thrombosis. Methods and results: Nitinol stents were expanded to 2 mm in diameter in two perfusion chambers in a parallel shunt and exposed to flowing arterial blood at 2100 s^-1 to generate stent thrombi (n=224 perfusion runs). Dethrombotic effects were assessed during treatment with saline and combined treatment with aspirin and heparin. One stent was exposed to ultrasound (27 kHz, 1.4 W/cm²), while the other was not. Stent thrombi were weighed before and after treatment. There was no significant effect of ultrasound during saline infusion. Treatment with aspirin+heparin alone reduced thrombus weight by 37±25% (18.9±6.1 to 11.8±7.7 mg, p<0.0001). Combined treatment with aspirin+heparin+ultrasound produced a 49±23% reduction in thrombus weight (19.0±6.3 to 9.6±7.8 mg, p<0.0001). The reduction in thrombus weight was significantly greater in aspirin+heparin+ultrasound compared with aspirin+heparin alone (p=0.04). Conclusions: Transcutaneous ultrasound significantly enhances dethrombotic effect of aspirin plus heparin on preformed stent thrombi. These findings suggest the potential of ultrasound as an adjunct to antithrombotic therapy to improve effectiveness without increasing the risk of bleeding complications during treatment of vascular thrombosis.