Abstract 17313: Multiparametric Cardiac MRI Documents Reduced LV Remodeling and Improved Contractile Function in Regions Adjacent to the Infarct After Pharmacologic Immunomodulation via Adenosine 2a Receptor Stimulation

Abstract

Introduction: Agonists of the Adenosine 2a Receptor (A2aR) are used clinically as pharm-stress agents for perfusion imaging, but they are also potent immunomodulators that reduce the size of acute MI when administered at reperfusion in both large and small animal models of MI. Hypothesis: Sustained administration of an A2aR agonist can reduce post-MI LV remodeling and improve cardiac strain even when treatment is withheld until after infarct size has stabilized. Methods: Two groups of mice were studied: C57BL/6 mice treated with Vehicle or a highly selective A2aR agonist (ATL313). All mice received 1h coronary occlusion and 28d of reperfusion. ATL313 was administered for 28 days by subcutaneous micro-osmotic pumps implanted after MI. All mice underwent 7T CMR imaging at baseline and 2, 7 & 28 days post-MI. CMR included short-axis black-blood cines covering the entire heart, with mid-ventricular cine DENSE for circumferential strain (Ecc). Late Gd-enhanced (LGE) inversion recovery imaging was performed on Days 2&7 and molecular imaging with a collagen-targeted Gd contrast agent (EP3533) on Days 14&28. Mice with Day 2 LGE infarct sizes less than 22% or >42% LV mass were excluded from analysis. Results: Examples of LGE and DENSE analysis are shown in Panels A&B. Day 2 infarct size was similar between groups (ATL313 (n=9): 35±2 vs Vehicle (n=8): 34±2, mean±SEM, p=NS). In panel C, ATL313 significantly improved LV end-systolic volume as early as 2 days post-MI (mean±SEM, *p<0.05 vs Vehicle). In panel D, ATL313 improved Day 2 Ecc in adjacent zones vs. Vehicle (-10±2 vs -6±2%, *p<0.05). In panel E, ATL313 reduced LV mass at Day 28 vs Vehicle (121±7 vs 143±7mg, *p<0.05). Conclusions: Pharmacologic immunomodulation with an A2aR agonist inhibits LV remodeling, improves contractile function in infarct-adjacent regions at Day 2 post-MI and reduces LV mass at Day 28. Combined with previous work, these results suggest that A2aR stimulation may prove beneficial in both acute and sub-acute MI.