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European Heart Journal Advance Access originally published online on May 26, 2007
European Heart Journal 2007 28(16):2011-2017; doi:10.1093/eurheartj/ehm176
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Detection of recent myocardial ischaemia by molecular imaging of P-selectin with targeted contrast echocardiography

Beat A. Kaufmann1, Christopher Lewis2, Aris Xie1, Ayoub Mirza-Mohd2 and Jonathan R. Lindner1,*

1 Cardiovascular Division, UHN-62, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
2 University of Virginia, Charlottesville, VA, USA

Received 22 December 2006; revised 21 March 2007; accepted 13 April 2007; online publish-ahead-of-print 26 May 2007.

* Corresponding author. Tel: +1 503 494 8750; fax: +1 503 494 8550. E-mail address: lindnerj{at}ohsu.edu

Aims: We hypothesized that molecular imaging of endothelial P-selectin expression with targeted myocardial contrast echocardiography (MCE) could identify recently ischaemic myocardium without infarction.

Methods and results: The microvascular behaviour of P-selectin-targeted (MBp) and control (MBc) microbubbles was assessed by intravital microscopy of the cremaster muscle in mice. Targeted MCE imaging with MBp and MBc was performed in mice after brief left anterior descending (LAD) occlusion and reperfusion and in open- and closed-chest controls. Regional wall motion and perfusion by MCE were assessed during occlusion and after reperfusion. On intravital microscopy, ischaemia–reperfusion produced a 10-fold increase (P < 0.01) in venular attachment for MBp. Attachment for MBc was rare. With myocardial ischaemia–reperfusion, LAD occlusion produced hypoperfusion and wall motion abnormalities that resolved after 45 min of reperfusion. At 45 min, signal enhancement in the post-ischaemic region was four-fold greater (P < 0.05) for MBp vs. MBc. MBp produced low-level enhancement in non-ischaemic myocardium in all open-chest animals, suggesting P-selectin expression from surgical cardiac exposure.

Conclusion: Molecular imaging of P-selectin with targeted MCE can identify the presence of recently ischaemic myocardium in the absence of necrosis and after resolution of hypoperfusion and post-ischaemic stunning. This technique can potentially provide a method for risk stratifying patients with acute chest pain.

Key Words: Contrast echocardiography • Myocardial ischaemia • Reperfusion injury • Molecular imaging


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