Abstract 13453: Myocardial Contrast Echocardiography Molecular Imaging of Selectins Can Detect Recent Myocardial Ischemia Hours After Resolution of Hypoperfusion
Background: Molecular imaging techniques are being developed in order to detect recent ischemia in patients with chest pain. These techniques will be of greatest clinical value if they can detect signal late after resolution of ischemia. The aim of this study was to determine whether pan-selectin targeting with myocardial contrast echocardiography (MCE) with microbubbles bearing human-ready recombinant glycoprotein on the surface of the microbubbles can be used to detect myocardial ischemia late after resolution.
Methods: In 8 wild-type mice, myocardial ischemia was produced by 10 min ligation of the LAD. Four mice served as non-ischemic controls, two of which underwent sham thoracotomy. Regional wall motion was assessed with high frequency echocardiography at 15 and 180 min after reflow. At 90 and 180 min after reflow, MCE molecular imaging was performed with microbubbles bearing either P-selectin monoclonal antibody (MBAb) or recombinant dimeric P- and E-selectin ligand PSGL-1 (MBPSGL). After molecular imaging was complete, the risk area (RA) was defined after intravenous injection of fluorescent nanospheres during repeat LAD ligation.
Results: The average RA was 46% (range 24-61%) of the total myocardial area at the mid LV short-axis plane. Immediately after reperfusion, myocardial radial thickening was reduced in the RA compared to remote non-ischemic areas (12±4% vs 33±3%; p<0.01) but recovered to normal by 180 min (25±3% vs 28±3%; p=ns). On targeted MCE, both MBPSGL and MBAb produced strong signal enhancement in the post-ischemic RA at 90 min (11.6±4.4 vs. 8.1±3.1 IU) and 180 min (9.1±4 vs 7.8±3.7 IU) after reflow. Contrast enhancement on molecular imaging correlated spatially with the RA. Signal for MBPSGL and MBAb was low in the remote territories (2.3±1.1; 2.2±0.6 IU and 1.7±0.8; 0.9±0.5 IU at 90 and 180 min). There was no significant enhancement seen in baseline control animals (<1 IU) or after sham surgery (0.2; 0.2 IU).
Conclusions: Molecular imaging with a human-ready pan-selectin-targeted microbubble is able to detect recent myocardial ischemia for several hours after reperfusion. This technique may provide a method for the detection of myocardial ischemia in patients with a history of chest pain even hours after resolution of hypoperfusion.
- © 2011 by American Heart Association, Inc.