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

Abstract

We hypothesized that molecular imaging of endothelial P-selectin expression with targeted myocardial contrast echocardiography (MCE) could identify recently ischaemic myocardium without infarction. The microvascular behaviour of P-selectin-targeted (MB(p)) and control (MB(c)) microbubbles was assessed by intravital microscopy of the cremaster muscle in mice. Targeted MCE imaging with MB(p) and MB(c) 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 MB(p). Attachment for MB(c) 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 MB(p) vs. MB(c). MB(p) produced low-level enhancement in non-ischaemic myocardium in all open-chest animals, suggesting P-selectin expression from surgical cardiac exposure. 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.