Abstract 2153: Molecular Imaging of Endothelial Cell Activation Detects Recent Myocardial Ischemia: Implications for Early Risk Stratification
Background: Current methods for detecting acute coronary syndromes are limited by poor specificity and are frequently non-diagnostic. We hypothesized that molecular imaging of endothelial cell activation by myocardial contrast echocardiography (MCE) and P-selectin-targeted microbubbles (MBp) could be used to detect recent myocardial ischemia even after resolution of hypoperfusion and post-ischemic stunning.
Methods: The binding properties of microbubbles were assessed by intravital microscopy of mouse cremaster muscle. Dual channel epifluorescent microscopy was performed after IV injection of MBp and control microbubbles (MBc) in either non-ischemic muscle or muscle undergoing 15 min of vascular pedicle occlusion and 45 min of reflow. Targeted MCE with MBp and MBc was performed in 12 mice undergoing 10 min of LAD ischemia and 45 min of reflow, and in 6 control mice (3 sham operated, 3 closed chest). Regional perfusion and wall motion were assessed by MCE during coronary occlusion and after reflow.
Results: On intravital microscopy, attachment of MBp to venular endothelium was greater in ischemic versus non-ischemic muscle (73±28 vs 7±6 mm−2, p<0.01). Attachment for MBc was essentially absent. In animals undergoing LAD ischemia, anterior hypoperfusion and abnormal wall motion resolved in all animals after 45 min of reflow. Signal enhancement after ischemia-reperfusion for MBp was greater in the risk area compared to the remote non-ischemic area (11.5±4.5 vs 6.5±3.9, p<0.05). Signal in the risk area was greater for MBp than for MBc (4.0±3.6, p<0.05). Studies with size-optimized (all <5 μm) microbubbles to prevent their non-specific physical entrapment eliminated signal in the risk area for MBc but not MBp (0.2±0.2 vs 1.7±1.0, p<0.05). Imaging in sham operated controls demonstrated low-level enhancement in all regions, indicating that MBp signal in the non-ischemic region was from open chest surgery. Minimal enhancement occurred for either agent in closed chest controls.
Conclusions: Imaging of P-selectin with targeted MCE can identify the presence of recent ischemia in the absence of necrosis and after resolution of hypoperfusion and stunning. This strategy may be useful for evaluating patients who present after resolution of symptoms.