Abstract 215: Systemic Inflammation Exacerbates Electrophysiological Remodeling and Arrhythmia Following Myocardial Infarction

Introduction: Inflammatory macrophages infiltrate the heart following myocardial infarction (MI) and secrete proteases and cytokines that may contribute to adverse electrophysiological remodeling. Atherosclerosis, the leading cause of MI, is associated with elevated systemic inflammation. Using a novel combination of optical mapping and molecular imaging, we sought to determine if systemic inflammation exacerbates electrophysiological remodeling and arrhythmogenesis. Methods: A protease activatable fluorescent sensor (Prosense680) was injected I.V. 4 days post MI in mice. Optical mapping of transmembrane potential was performed 5 days post MI on Langendorff-perfused hearts to assess electrophysiology. Fluorescence reflectance imaging of Prosense680 was then performed to visualize and quantify inflammatory protease activity. Lipopolysaccharide (LPS:10 μ g/day, n=6) was injected I.P. to promote systemic inflammation or saline as control (SAL, n=7). Results: Inflammation levels were greater in MI+LPS vs MI+SAL hearts (5.626±1.5 vs 1.73±0.25 A.U., p<0.02) and negligible in sham-operated hearts (SH, n=4). MI+LPS hearts had prolonged action potential (AP) duration vs MI+SAL vs SH (62±4.5 vs 56±1.8 vs 45±3.7 ms, p<0.05) and increased AP rise time (5.5±0.5 vs 4.2±0.2 vs 2.9±0.3 ms, p<0.05). A single premature pacing stimulus induced ventricular tachycardia in 67%(4 of 6) of MI+LPS vs 15%(1 of 7) MI+SAL vs 0% (0 of 4) SH, p<0.02. Conclusions: Elevated post-MI inflammation may contribute to electrophysiological remodeling and arrhythmias. These findings have important implications for the etiology of post-MI arrhythmias in humans with systemic inflammation.