Abstract 3424: A Potent Anti-Inflammatory Agent is as Effective as the Combination of ACE-Inhibition and Beta-Blockade at Reducing Post-Infarct Left Ventricular Remodeling in a Murine Model of Reperfused Myocardial Infarction: A Cardiac MR Study
Introduction: Agonists of the Adenosine 2A Receptor (A2AR) are potent anti-inflammatory and cardioprotective agents. This study tests the hypothesis that selective A2AR activation can preserve post-MI cardiac function similar to combined ACE inhibition and beta-adrenergic receptor blockade (AI+BB) therapy.
Methods: Three groups of mice were studied: 6 Untreated C57BL/6, 5 treated with ATL313 (A2AR agonist) and 7 treated with combined AI+BB. All mice received 1h coronary occlusion and 28d of reperfusion. ATL313 was administered by subcutaneous micro-osmotic pump starting 1h post-MI until Day 14 post-MI. The AI+BB combination of Captopril+Metoprolol was delivered similarly until Day 28. All mice underwent 4.7T CMR imaging before and at 1, 7 & 28 days post-MI. CMR included short-axis black-blood cines covering the entire heart. On Day 1, Gd-DTPA was infused for Gd-enhanced inversion recovery imaging. LV volumes, EF & LV mass were measured from cine images. Day 1 infarct size was measured as %LV mass from Gd-enhanced CMR.
Results: Day 1 mean infarct size was similar in the 3 groups (Untreated: 40±4, AI+BB: 44±5%, ATL313: 41±3, p=NS). Panels A–C show Day 28 ED images with A: Untreated, B: AI+BB & C: ATL313. LV dilation and wall thinning are evident in Untreated while both were preserved in AI+BB & ATL313 groups. Panels D–G show means + SEM bars for EDV, ESV, EF & LV mass where * denotes p<0.05 vs Untreated. Both AI+BB & ATL313 reduced EDV & ESV at Day 7 & 28 and LV mass at Day 28. ATL313 improved EF on Day 1 & 28, while AI+BB improved EF on Day 7 & 28.
Conclusions: Selective activation of A2AR reduces post-MI LV remodeling comparable to AI+BB. A2AR-stimulation also preserves Day 1 EF better than AI+BB.