Abstract 15170: Persistent Microvascular Obstruction Leads to Localized Iron Deposition and Active Inflammation Within Chronic Myocardial Infarctions

Abstract

Introduction: The mechanism by which persistent microvascular obstruction (PMO) post myocardial infarction (MI) exerts adverse long-term effects is not well understood. Hypothesis: We hypothesized that PMO, with or without reperfusion hemorrhage, can resolve into iron deposition within chronic MI (CMI) territories, and is associated with prolonged inflammation and adverse LV remodeling. Methods: Canines subjected to reperfused (n=17) and non-reperfused (n=16) MI underwent Cardiovascular Magnetic Resonance (CMR) at 7 (acute) and 56 days (chronic) post-MI. Cine, T2*-weighted and Late Gadolinium Enhancement images were used to characterize LV remodeling (End-Diastolic Sphericity Index (EDSI)), iron and PMO respectively. Histological analysis was used to examine chronic inflammation. Results: In the reperfused group, 9 canines had PMO and hemorrhage with subsequent chronic iron deposition (PMO+/T2*+), while 4 canines had no PMO, hemorrhage, or chronic iron deposition (PMO-/T2*-). The remaining 4 canines had PMO without hemorrhage (PMO+/T2*-), but all subsequently had chronic iron deposition. In the non-reperfused group, 15 canines had PMO, and acute and subsequent chronic iron deposition (NR-PMO+/T2*+); 1 canine had no PMO, acute or chronic iron deposition (NR-PMO-/T2*-). In both groups, PMO volume was significantly associated with both acute and chronic iron volumes (p<0.001 all cases). In both groups, infarct and iron volumes measured in both acute and chronic phases were significant predictors of change in EDSI between acute and chronic phases (p<0.01 all cases). Histological sections of the harvested hearts post day 56 CMR showed extensive newly recruited macrophage, IL-1β, TNF-α and MMP-9 activities highly localized with iron in CMI regions (p<0.001 all cases). Conclusions: PMO, with or without reperfusion hemorrhage, can lead to iron deposition within CMIs, and is associated with active inflammation and adverse LV remodeling in canines.