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Abstract
Sympathetic denervation following ischemia-reperfusion (I-R) injury is a strong predictor of arrhythmias and sudden cardiac death, yet the underlying mechanisms remain unclear. This study identifies chondroitin sulfate proteoglycans (CSPGs) in the infarcted myocardium as inhibitors of sympathetic axon regeneration and demonstrates that loss or pharmacologic inhibition of their receptor, PTPσ, restores sympathetic innervation. Reinnervation markedly reduced arrhythmia susceptibility and prevented electrophysiological remodeling, including Ca²⁺ mishandling, as shown by optical mapping. These findings reveal sympathetic reinnervation as protective post-I-R and establish PTPσ as a promising therapeutic target to prevent arrhythmias after myocardial infarction.