Abstract 10484: Effects of Combined Platelet and Fibrin Targeted Microbubbles on the Success of Ultrasound and Microbubble Mediated Thrombus Dissolution of Older Thrombi
Background: The effectiveness of fibrinolytic therapy (TPA) decreases as thrombus age increases. This appears to be related to contraction of platelets, which pull fibrin strands inward leading to clot retraction. We hypothesized that the shearing effect of ultrasound induced cavitation of microbubbles (MB) would improve TPA effectiveness in aged thrombi, especially if MB were more adherent to the thrombus.
Methods: A hybrid- targeted MB was developed (NuvOx Pharma), which binds to both the glycoprotein 2b/3a receptor (GPIIBIIIA) in platelets and exposed fibrin. Thrombi were prepared from porcine arterial blood,mixed with thrombin (2 units) and aged for 6 hours. These thrombi were then embedded in branching silastic vessels (2.6 mm internal diameter) which connected to a flow system. The flow system was perfused with 10% fresh pig plasma and recombinant TPA (330 ug). A 10 cm tissue-mimicking phantom (TMP) was placed over the thrombosed vessel and a diagnostic three-dimensional transducer (Philips iE 33) aligned with the vessel using a positioning system. A 0.5% dilution of either hybrid targeted MB or non targeted microbubbles (Definity; Lantheus) were visualized with low mechanical index (MI) imaging (0.1MI) which then guided the timing of the high MI impulses (>1.0). Total treatment time was 10 minutes. TPA alone and 3D plus TPA without MB were used as control. Percent thrombus dissolution (%TD) was calculated by comparison of thrombus mass before and after treatment.
Results: 48 aged thrombi were tested. Guided 3D ultrasound and hybrid MB significantly increased the %TD compared to rt-PA alone (p=0.01)and rt-PA with 3D (both p=0.01; ANOVA), with nearly 50% of dissolution of the aged thrombus in the 10 minute treatment window (Figure).
Conclusions: 3D ultrasound and hybrid-targeted microbubbles increase the efficacy to TPA in dissolving aged thrombi.
- © 2010 by American Heart Association, Inc.