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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 ±1 6 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. Methods Female fvb/n mice were divided into three experimental groups. The A6 PREMI group underwent subcutaneous pump implant that delivered A6 two days before LAD ligation. The A6 MI and vehicle (VEH) groups underwent MI surgery simultaneously with subcutaneous A6 or vehicle pump implantation. Pump rate was 10 ng/kg/day over a course of two weeks, and all groups had their pumps reimplanted after two weeks. Cardiac MRI (CMR) was performed at 1, 2, and 4 weeks post MI. ANX-SPIO was delivered via tail vein one day prior to CMR to simultaneously

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