Myocardial ischemic memory imaging with molecular echocardiography.
BACKGROUND
Diagnosing acute coronary syndrome in patients presenting with chest discomfort is a challenge. Because acute myocardial ischemia/reperfusion is associated with endothelial upregulation of leukocyte adhesion molecules, which persist even after ischemia has resolved, we hypothesized that microbubbles designed to adhere to endothelial selectins would permit echocardiographic identification of recently ischemic myocardium.


RESULTS
Lipid microbubbles (diameter, 3.3+/-1.7 microm) were synthesized. The selectin ligand sialyl Lewis(x) was conjugated to the microbubble surface (MB(sLex)). Control bubbles (MB(CTL)) bore surface Lewis(x) or sialyl Lewis(c). Intravital microscopy of mouse cremaster muscle was performed after intravenous injection of MB(sLex) (n=11) or MB(CTL) (n=9) with or without prior intrascrotal tumor necrosis factor-alpha. There was greater adhesion of MB(sLex) to inflamed versus noninflamed endothelium (P = 0.0081). Rats (n=12) underwent 15 minutes of anterior descending coronary artery occlusion. After 30 minutes and 1 hour of reperfusion, high-mechanical-index nonlinear echocardiographic imaging was performed in which single frames were acquired at 3.5 and 4 minutes after intravenous injection of MB(sLex) or MB(CTL). Video intensity at 4 minutes was subtracted from that at 3.5 minutes to derive target-specific acoustic signal. MB(sLex) caused greater opacification in postischemic versus nonischemic myocardium at both time points (P < or = 0.002). Immunostaining confirmed endothelial P-selectin expression in the ischemic bed.


CONCLUSIONS
Echocardiographic identification of recently ischemic myocardium is possible using ultrasound contrast agents targeted to selectins. This may offer a new approach to the more timely and precise diagnosis of acute coronary syndrome in patients presenting with chest pain of uncertain cardiac origin.
Villanueva
Flordeliza S
FS
Cardiovascular Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. villanuevafs@msx.upmc.edu
Lu
Erxiong
E
Bowry
Shivani
S
Kilic
Sevgi
S
Tom
Eric
E
Wang
Jianjun
J
Gretton
Joan
J
Pacella
John J
JJ
Wagner
William R
WR
D000818:Animals; D002637:Chest Pain / Q000209:etiology; D003287:Contrast Media; D003937:Diagnosis, Differential; D004452:Echocardiography / Q000379:methods*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D045423:Microbubbles; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009844:Oligosaccharides; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D000080506:Sialyl Lewis X Antigen; D015854:Up-Regulation
D003287:Contrast Media; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen