Myocardial ischemic memory imaging with molecular echocardiography

Area of Science:

• Cardiovascular Imaging
• Biomaterials Science
• Diagnostic Medicine

Background:

• Diagnosing acute coronary syndrome (ACS) presents challenges due to difficulties in identifying myocardial ischemia.
• Leukocyte adhesion molecules are upregulated on the endothelium during ischemia/reperfusion, persisting after the ischemic event.

Purpose of the Study:

• To develop microbubbles targeted to endothelial selectins for echocardiographic identification of recently ischemic myocardium.
• To evaluate the efficacy of these targeted microbubbles in a rat model of myocardial ischemia.

Main Methods:

• Synthesized lipid microbubbles conjugated with sialyl Lewis(x) (MB(sLex)) and control microbubbles (MB(CTL)).
• Assessed microbubble adhesion to inflamed endothelium using intravital microscopy in mice.
• Performed echocardiographic imaging in rats after coronary artery occlusion and reperfusion, injecting MB(sLex) or MB(CTL).

Main Results:

• MB(sLex) demonstrated significantly greater adhesion to inflamed endothelium compared to control bubbles.
• Echocardiography revealed greater opacification in postischemic myocardium using MB(sLex) compared to MB(CTL).
• Immunostaining confirmed P-selectin expression in the ischemic myocardium.

Conclusions:

• Echocardiographic identification of recently ischemic myocardium is achievable with selectin-targeted ultrasound contrast agents.
• This approach holds promise for earlier and more precise diagnosis of acute coronary syndrome.
• Offers a potential new diagnostic tool for patients with chest pain of uncertain cardiac origin.