Abstract 11502: Molecular Magnetic Resonance Imaging Allows Detection of Reduced Ischemia-Reperfusion Injury in P2Y12 Knockout Mice
Introduction: Magnetic resonance imaging (MRI) for both inflammation and necrosis after coronary artery occlusion and recanalization is not availible by now. Non-invasive evaluation of myocardial ischemia-reperfusion (I/R) injury and therapeutic interventions would be of great clinical and prognostic interest. Therefore, we evaluated the impact of a simulated platelet inhibition on I/R injury by an innovative strategy of molecular MRI and compared these findings with established infarct size readout-methods.
Methods and Results: I/R injury was induced in C57BL/6N (WT) and P2Y12-/- mice by 50 minute temporary ligation of the ,,left anterior descending coronary artery“ (LAD). Two hours after reperfusion, MRI of mouse hearts pre and post injection of a contrast agent consisting of antibodies against ligand-induced binding sites of the activated platelet GPIIb/IIIa conjugated to microparticles of iron oxide (LIBS-MPIO), or a control antibody conjugated to MPIOs (control-MPIO) was performed. Thereafter, gadolinium (Gd) was injected.
Activated platelets were specifically detectable via a significant signal effect caused by LIBS-MPIO in the area of LAD occlusion in WT mice, whereas in P2Y12-/- mice no signal increase was found. Gd allowed in all groups the detection of myocardial necrosis. The extent of necrosis was significantly lower in P2Y12-/- mice (p<0.01) as well as in HE staining (p<0.001). Quantification of microthrombi and platelet-neutrophil-conjugates confirmed significantly less accumulation in P2Y12-/- mice (p<0.001), and the amount of bound MPIOs was significantly reduced to the level of WT-mice in P2Y12-/- mice (p<0.01). Echocardiography demonstrated a trend towards better preserved ejection fraction in P2Y12-/- mice (p<0.1). In Monolite Blue/TTC staining, infarct size of the area at risk was significantly lower in P2Y12-/- mice (p<0.05).
Conclusions: This dual approach of molecular MRI for detection of activated platelets and myocardial necrosis discloses reduced I/R injury in a simulated platelet inhibition strategy in mice, reflecting findings in histology with a high accuracy. Such a non-invasive imaging strategy is of clinical and prognostic interest, and shows the potential to monitor therapeutical interventions.
Author Disclosures: A. Maier: None. D. Dürschmied: None. D. von Elverfeldt: None. K. Peter: None. C. Bode: None. C. von zur Muhlen: None.
- © 2014 by American Heart Association, Inc.