Myocardial infarction (MI) induces neural and electrical remodeling at scar border zones. The impact of focal MI on global functional neural remodeling is not well understood. Sympathetic stimulation was performed in swine with anteroapical infarcts (MI; n ϭ 9) and control swine (n ϭ 9). A 56-electrode sock was placed over both ventricles to record electrograms at baseline and during left, right, and bilateral stellate ganglion stimulation. Activation recovery intervals (ARIs) were measured from electrograms. Global and regional ARI shortening, dispersion of repolarization, and activation propagation were assessed before and during sympathetic stimulation. At baseline, mean ARI was shorter in MI hearts than control hearts (365 Ϯ 8 vs. 436 Ϯ 9 ms, P Ͻ 0.0001), dispersion of repolarization was greater in MI versus control hearts (734 Ϯ 123 vs. 362 Ϯ 32 ms 2 , P ϭ 0.02), and the infarcted region in MI hearts showed longer ARIs than noninfarcted regions (406 Ϯ 14 vs. 365 Ϯ 8 ms, P ϭ 0.027). In control animals, percent ARI shortening was greater on anterior than posterior walls during right stellate ganglion stimulation (P ϭ 0.0001), whereas left stellate ganglion stimulation showed the reverse (P ϭ 0.0003). In infarcted animals, this pattern was completely lost. In 50% of the animals studied, sympathetic stimulation, compared with baseline, significantly altered the direction of activation propagation emanating from the intramyocardial scar during pacing. In conclusion, focal distal anterior MI alters regional and global pattern of sympathetic innervation, resulting in shorter ARIs in infarcted hearts, greater repolarization dispersion, and altered activation propagation. These conditions may underlie the mechanisms by which arrhythmias are initiated when sympathetic tone is enhanced. autonomic nervous system; sympathetic nerves; cardiac innervation; neural remodeling REMODELING of the cardiac sympathetic nervous system after myocardial infarction (MI) has been linked to ventricular arrhythmias in animal models (29) and in humans (4,12,24). Modulation of cardiac sympathetic signaling is a major therapeutic strategy to prevent and treat ventricular arrhythmias (1,8,22). Despite its importance, the global electrophysiological consequences of postinfarct neural remodeling from a focal infarct remain poorly characterized.Patchy myocardial scars with surviving islands of myocytes characterize human infarcts (10, 17). Heterogeneous intramyocardial sympathetic nerve sprouting at scar border zones leads to labile repolarization, increased peak Ca 2ϩ current, and susceptibility to ventricular fibrillation in hypercholesterolemic rabbits (15). Increased transmural dispersion of repolarization has also been reported (13, 28), along with alterations in transient outward and inward rectifier K ϩ currents (21) in a postinfarct model with nerve sprouts.However, the electrophysiological responses to sympathetic activation exhibited by myocytes at and remote to a focal infarction have not been characterized. Specifically, the functi...