Abstract 352: Evaluation of ICAM-1 Expression for a Recent Myocardial Ischemia in Late Time Window With Ultrasound Molecular Imaging
Background: Evaluation of chest pain suggestive of myocardial ischemia is problematic. Previous studies show ultrasound molecular imaging with microbubbles targeted to the endothelial P-selectin is capable for the detecting of recently ischemic myocardium in an early time window (within 1 hour) of reperfusion. However, the ability of this technique in detecting of recent myocardial ischemia in late time window of reperfusion has not been defined. We, therefore, hypothesized that microbubbles designed to adhere to endothelial intercellular adhesion molecule-1 (ICAM-1) could identify recent ischemic myocardium in late time window (8–24 hour) of reperfusion.
Method: 20 mice (C57/BL, male) were equally divided into sham thoracotomy and three test groups with 15-minute of anterior descending coronary artery occlusive myocardial ischemia followed by 1, 8 and 24 hours of reperfusion (I/R). Lipid-based microbubbles were conjugated to anti-mice ICAM-1 (MBICAM) or isotype control antibody (MBISO). Contrast-enhanced ultrasound imaging (CEU) was performed in the heart of all mice after intravenous injection of MBICAM or MBISO in random at the 30 minutes interval. Myocardial video intensity (VI) from the microbubbles targeted to the endothelial ICAM-1 was measured. All hearts of experimental mice were harvested for immunohistochemial examination.
Results: A marked expression of ICAM-1 on vascular endothelium was only noted in the ischemic area of both 8 and 24 hours I/R groups, but it was not obviously evident beyond that. As expected, in both 8 and 24 hours I/R groups, VI of the ischemic myocardium with MBICAM was significantly higher exceeded to 150% than that of the ischemic myocardium with MBISO (P<0.05) and that of the non-ischemic myocardium with MBICAM (P<0.05). While, there was no obvious difference between two contrast agents in sham and 1 hour I/R groups.
Conclusion: Ultrasound molecular imaging with microbubbles targeted to ICAM-1 could provide reliable evidence to detect a recent myocardial ischemic event in late time window of reperfusion, and this evidence could persist 24 hours or even longer.