Restorative effects of alpha-1A adrenergic are detectable using T2* and targeted nanoparticles in a mouse myocardial infarction (MI) model

Background Apoptosis is believed to play a major role in the progressive weakening of the peri-infarct and remote zone myocardium after myocardial infarction (MI). Our laboratory previously developed an in vivo, MRI-detectable apoptosis probe. Annexin-V (ANX), which binds to cells undergoing apoptosis, was conjugated to superparamagnetic iron oxide (SPIO) nanoparticles, allowing for the non-invasive detection of early apoptotic cell populations (ANX-SPIO r1: 8.6 ± 0.61 mM-1 s-1 and r2: 326 ± 16 mM-1 s-1). In recent work, we demonstrated A61603 (A6), an a1adrenergic receptor agonist, can rescue cardiac cells from apoptosis through activation of the cardio-protective ERK pathway. We tested whether pre-treatment with A6 was able to prevent the functional decline after MI via an antiapoptotic mechanism, and whether T2* cardiac MRI, using ANX-SPIO, was sensitive to this dynamic protective effect. Our hypothesis was that A6 pre-treatment protects against MI-induced cardiomyopathy more effectively than A6 treatment after MI.