High-Resolution 3-Dimensional Reconstruction of the Infarct Border Zone Impact of Structural Remodeling on Electrical Activation

Rationale: Slow nonuniform electric propagation in the border zone (BZ) of a healed myocardial infarct (MI) can give rise to reentrant arrhythmia. The extent to which this is influenced by structural rather than cellular electric remodeling is unclear. Objective: To determine whether structural remodeling alone in the infarct BZ could provide a substrate for re-entry by (i) characterizing the 3-dimensional (3D) structure of the myocardium surrounding a healed MI at high spatial resolution and (ii) modeling electric activation on this structure. Methods and Results: Anterior left ventricular (LV) infarcts were induced in 2 rats by coronary artery ligation. Three-dimensional BZ volume (4.1 mm(3) and 5.6 mm(3)) were imaged at 14 days using confocal microscopy. Viable myocytes were identified, and their connectivity and orientation were quantified. Preserved cell networks were observed in the subendocardium and subepicardium of the infarct. Myocyte tracts traversed the BZ, and there was heavy infiltration of collagen into the adjacent myocardium. Myocyte connectivity decreased by approximate to 65% over 250 mu m across the BZ. This structure was incorporated into 3D network models on which activation was simulated using Luo-Rudy membrane dynamics assuming normal cellular electric properties. Repetitive stimulation was imposed at selected BZ sites. Stimulus site-specific unidirectional propagation occurred in the BZ with rate-dependent slowing and conduction block, and reentry was demonstrated in one substrate. Activation times were prolonged because of tract path length and local slowing. Conclusions: We have used a detailed image-based model of the infarct BZ to demonstrate that structural heterogeneity provides a dynamic substrate for electric reentry. (Circ Res. 2012;111:301-311.)