Published Online
on January 8, 2007

A more recent version of this article appeared on January 23, 2007

This Article Full Text (PDF) All Versions of this Article: 115/3/345    most recent CIRCULATIONAHA.106.633917v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Villanueva, F. S. Articles by Wagner, W. R. Search for Related Content PubMed PubMed Citation Articles by Villanueva, F. S. Articles by Wagner, W. R. Pubmed/NCBI databases Substance via MeSH Related Collections Cardiovascular imaging agents/Techniques Imaging Ischemic biology - basic studies Acute coronary syndromes Echocardiography Coronary circulation Related Article

Submitted on April 14, 2006
Accepted on November 9, 2006

Myocardial Ischemic Memory Imaging With Molecular Echocardiography

Flordeliza S. Villanueva MD^*, Erxiong Lu MD, PhD, Shivani Bowry BS, Sevgi Kilic PhD, Eric Tom BS, Jianjun Wang PhD, Joan Gretton BS, John J. Pacella MS, MD, and William R. Wagner PhD

From the Cardiovascular Institute, Department of Medicine, University of Pittsburgh School of Medicine (F.S.V., E.L., S.B., S.K., J.W., J.G., J.J.P), and Department of Bioengineering (E.T., W.R.W.) and McGowan Institute for Regenerative Medicine (W.R.W.), University of Pittsburgh, Pittsburgh, Pa.

^* To whom correspondence should be addressed. E-mail: villanuevafs{at}msx.upmc.edu.

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.

Methods and Results--Lipid microbubbles (diameter, 3.3±1.7 µm) 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-. 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 (P0.002). 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.

Key words: cell adhesion molecules • contrast media • echocardiography • endothelium • imaging • ischemia

Related Article:

Issue Highlights
Circulation 2007 115: 287. [Extract] [Full Text]

This article has been cited by other articles:

				J. R. Lindner Contrast ultrasound molecular imaging of inflammation in cardiovascular disease Cardiovasc Res, November 1, 2009; 84(2): 182 - 189. [Abstract] [Full Text] [PDF]

				D. P. Cormode, T. Skajaa, Z. A. Fayad, and W. J.M. Mulder Nanotechnology in Medical Imaging: Probe Design and Applications Arterioscler Thromb Vasc Biol, July 1, 2009; 29(7): 992 - 1000. [Abstract] [Full Text] [PDF]

				A. E. Weyman The year in echocardiography. J. Am. Coll. Cardiol., April 28, 2009; 53(17): 1558 - 1567. [Full Text] [PDF]

				M. Nahrendorf, D. E. Sosnovik, B. A. French, F. K. Swirski, F. Bengel, M. M. Sadeghi, J. R. Lindner, J. C. Wu, D. L. Kraitchman, Z. A. Fayad, et al. Multimodality Cardiovascular Molecular Imaging, Part II Circ Cardiovasc Imaging, January 1, 2009; 2(1): 56 - 70. [Full Text] [PDF]

				A. J. Sinusas, F. Bengel, M. Nahrendorf, F. H. Epstein, J. C. Wu, F. S. Villanueva, Z. A. Fayad, and R. J. Gropler Multimodality Cardiovascular Molecular Imaging, Part I Circ Cardiovasc Imaging, November 1, 2008; 1(3): 244 - 256. [Full Text] [PDF]

				S. Kaul Myocardial Contrast Echocardiography: A 25-Year Retrospective Circulation, July 15, 2008; 118(3): 291 - 308. [Full Text] [PDF]

				A. E. Weyman The Year in Echocardiography J. Am. Coll. Cardiol., March 25, 2008; 51(12): 1221 - 1229. [Full Text] [PDF]

				T. R. Porter Cardiovascular Imaging of Remote Myocardial Ischemia: Detecting a Molecular Trace of Evidence Left Behind Circulation, January 23, 2007; 115(3): 292 - 293. [Full Text] [PDF]