Abstract 15848: Regional Heterogeneity in Matrix Proteases and Inhibitors Occurs Within the Atrium Following Myocardial Infarction; Relation to Fibrillation Vulnerability
Background: : LV remodeling has been recognized as a key structural event following a myocardial infarction (MI) that can lead to LV failure, but less is known about remodeling events in the atria, a relevant issue since atrial fibrillation (AF) is not an uncommon event in the post-MI remodeling period. LV remodeling post-MI is characterized by regional changes in matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), causing non-uniformity within the matrix. In preliminary studies using an MMP radiotracer that detects sites of increased MMP activity, we identified an increase in MMP activity within certain sites of left (LA) and right (RA) atrium in a pig MI model, prompting us to test the hypothesis that a shift in MMP/TIMP expression pattern occurs through the LA-RA, thus associated with increased vulnerability to AF.
Methods/Results: MI was induced in pigs (25 kg; coronary ligation; n=10), and at 10-14 days post-MI, MMP/TIMP profiling using an mRNA array was performed in 9 pre-specified atrial sites traversing from the LA appendage (LAapp) to RA appendage (RAapp) using rtPCR. In MI pigs (n=4), a standardized atrial electrical stimulation protocol was performed. An additional 8 non-MI pigs served as controls. AF was inducible in 75% of the post-MI pigs but not in controls (p<0.05). Significant heterogeneity in MMP/TIMP expression occurred within specific atrial regions post-MI as a function of referent controls (Figure). An induction (red) of MMPs/TIMPs occurred in some atrial regions, whereas a reduction (blue) occurred at other regions. Differential MMP/TIMP induction occurred in the LAapp, a potential site for the genesis of AF.
Conclusion: These findings demonstrated a heterogeneous shift in MMP/TIMP within the atrium post-MI and were associated with increased AF vulnerability. This expression pattern within specific atrial regions would favor matrix proteolysis and instability, hence a substrate for the genesis of atrial re-entry rhythms.
- © 2013 by American Heart Association, Inc.