Abstract 20200: Detection of Recent Myocardial Ischemia Using a New Contrast Agent Designed for Human Application
Background: Detection of upregulated leukocyte adhesion molecules using antibody or carbohydrate ligands on microbubbles (MB) has proven the concept that recent myocardial ischemia can be identified with ultrasound molecular imaging. Clinical translation has been limited by immunogenicity or unfavorable chemistry of the targeting ligand. We sought to develop a new MB for ultimate human use in myocardial ischemic memory imaging.
Methods: Targeted biodegradable polymer MB (3.4±1.3μm) were prepared bearing a 12-mer synthetic peptide on the surface with specific E-selectin affinity (MBESEL). Control MB had scrambled peptide (MBCTL) or non-specific IgG (MBIgG). MB adhesion to cultured rat endothelial cells (EC) was assessed in a parallel plate flow system (n=3/condition). Intravital microscopy of rat cremaster microcirculation was performed after i.v.injection of each MB type under basal or activated conditions (scrotal TNFα 5μg) (n=3 rats/condition). To determine if binding events could be imaged, 6 rats had 15 min coronary artery occlusion. After 4 hrs reflow, each rat received separate i.v. boluses of MBESEL, MBCTL, and MBIgG. Non-linear echo imaging was performed 3 and 3.5 min later. Videointensity (VI) differences between the 2 time points was attributed to target-specific signal.
Results: MB ESEL adhesion was higher to activated vs normal EC (17±2 vs 5±3 MB/EC, p<0.01) in vitro. There was no difference in adhesion to activated vs normal EC when EC were perfused with MBCTL (5±2 vs 4±1 MB/EC, p=0.41) or MBIgG (2±1 vs 2±1/EC, p=0.48). Intravital microscopy showed greater adhesion of MBESEL to inflamed vs non-inflamed microcirculation (96±23 vs 34±8 MB/field, p<0.03), and minimal adhesion of MBCTL or MBIgG under any condition. Myocardial VI in the post-ischemic bed after MBESEL was higher vs the non-ischemic bed (12±3 dB vs 4±1 dB, p<0.02), and higher than that after MBCTL (4±1dB, p<0.03) or MBIgG (2±0 dB, p<0.02).
Conclusions: Echo identification of recently ischemic myocardium is possible using MB targeted to E-selectin via a short synthetic peptide. These data set the stage for clinical application of ultrasound ischemic memory imaging in the diagnosis of acute coronary syndrome in patients presenting with chest pain of uncertain etiology.
- © 2010 by American Heart Association, Inc.