Abstract 15543: Fibrin-Targeted Phase Shift Microbubbles Outperform Fibrin-Targeted Microbubbles for the Treatment of Microvascular Obstruction

Abstract

Introduction: Mortality from AMI has decreased in recent years; however, microvascular obstruction (MVO) occurs frequently, and is associated with rising post-AMI CHF, and has no definitive therapy. To address this urgent unmet need, we have developed an image-guided acute therapy, termed ‘sonoreperfusion’ (SRP), that resolves MVO via ultrasound-targeted microbubble cavitation (UTMC). We previously used standard-size, fibrin-targeted MBs and demonstrated enhanced reperfusion compared to standard-size, non-targeted MBs. However, phase shift microbubbles may allow greater clot penetration and perhaps more effective SRP, owing to their much smaller size Vs. standard MBs (~200 nm vs. 3 μm). Thus, we compared the SRP efficacies of fibrin-targeted phase shift microbubbles (FTPSMBs) (Microvascular Therapeutics, Inc), to standard-size fibrin-targeted microbubbles (FTMBs) for the treatment of MVO Methods: MVO of the rat hindlimb ( n=6 ) was created by injecting porcine microthrombi into the left femoral artery under contrast-enhanced ultrasound (CEUS) guidance. DEFINITY ® MBs (Lantheus Medical Imaging) were infused (2 mL/hr) through the right external jugular vein for CEUS. Following 10 min of stable MVO, a transducer was positioned vertically above the hindlimb to deliver therapeutic US pulses during concomitant administration of FTMBs/FTPSMBs (3 mL/hr). CEUS cine loops with burst replenishment were obtained at baseline (BL), 10 min post-MVO, and after each of the two SRP treatment sessions (TX1, TX2) and video intensities were analyzed (MATLAB_R2021a) Results: FTPSMBs treatment resulted in a greater increase in the blood volume (dB) and flow rate (dB/sec) than FTMB after each 10-minute treatment session (Figure 1) Conclusions: US-guided FTPSMB cavitation causes more rapid and complete reperfusion of MVO than FTMB, likely owing to their small size and more effective thrombus penetration. Studies to explore the underlying mechanisms are underway