Abstract 2901: Doppler Ultrasound Enhances the Thrombolytic Activity of Tissue-Plasminogen Activator-Loaded Echogenic Liposomes
Background: Ultrasound has been shown to enhance thrombolysis when used in conjunction with a thrombolytic agent. We have loaded echogenic liposomes (ELIP) with tissue plasminogen activator (tPA) and shown that mechanical non-imaging 1 MHz ultrasound can enhance thrombolysis in an in vitro clot model. This study aimed to evaluate the efficacy of clinical Doppler ultrasound to enhance the thrombolytic effect of our tPA-ELIP.
Materials and Methods: A standard reproducible whole blood porcine clot model was used. Clots were blotted dry, weighed, and placed in 10 ml fresh frozen porcine plasma. Clots were treated with tPA-ELIP with and without Doppler ultrasound (pulsed wave ultrasound, 6.6 MHz, 2 minute-treatment time). After 30 minutes, clots were similarly weighed. Data are reported as percent clot mass loss. Samples of the plasma were assayed for D-dimer levels.
Results: Exposure of tPA-ELIP to clinical Doppler ultrasound enhanced thrombolysis (p=0.015 vs. tPA alone or Doppler ultrasound alone; Figure⇓). There was a trend towards higher D-dimer levels in the clots treated with tPA-ELIP + clinical Doppler ultrasound, corresponding to the higher percent clot mass loss seen in this treatment group.
Conclusions: This study demonstrates the ability of clinical Doppler ultrasound to enhance the thrombolytic effect of our tPA-ELIP in an in vitro clot model. This demonstrates the potential to translate our novel thrombolytic technique of combining a thrombolytic-loaded contrast agent and ultrasound to patient care.