Abstract 1069: Doppler Ultrasound Enhances the Thrombolytic Activity of Tissue Plasminogen Activator-Loaded Echogenic Liposomes In Vivo
Ultrasound (US) enhances thrombolysis when combined with a thrombolytic and/or a contrast agent. We have demonstrated effective highlighting of clots using novel tissue plasminogen activator (tPA)-loaded echogenic liposomes (ELIP). tPA-ELIP results in effective thrombolysis in an in vitro clot model and Doppler US, to effect tPA release, enhances this lytic effect. This study aimed to evaluate the thrombolytic effect of tPA-ELIP with and without US in an in vivo clot model. Thrombus was created within the abdominal aorta (New Zealand white rabbits; n=4) using sodium ricinoleate and thrombin. Rabbits were randomized to receive tPA-ELIP (200 mcg tPA/5 mg lipid) or empty ELIP with or without Doppler US (5.7MHz, MI=0.5, 2 min). Thrombus was imaged and echogenicity analyzed before and after ELIP injection. Blood flow velocities (BFV) were measured using Doppler US at baseline, after clot formation, and serially after treatment up to 15 min. Data presented as % recanalization rate (treatment BFV/baseline BFV). tPA-ELIP highlighted thrombus in the abdominal aorta more effectively than empty ELIP or saline (control) [p<0.05]. US enhanced the thrombolytic effect of tPA-ELIP resulting in earlier and more complete recanalization rates [Figure⇓; p<0.001]. This study demonstrates effective highlighting of clots and thrombolytic effect of tPA-ELIP in an in vivo clot model. Clinical Doppler US enhances the thrombolytic effect of tPA-ELIP resulting in earlier and more complete recanalization rates. This study demonstrates the potential of this novel technique, combining a thrombolytic loaded contrast agent and ultrasound, to patient care.