This dissertation focuses on the impact of sympathetic remodeling and its effects on cardiacelectrophysiology. We were able to use a fully innervated rabbit heart preparation and whole heart dual-optical mapping to directly stimulate sympathetic nerve fibers to investigate the electrophysiological changes that occur in response to nerve stimulation. By using both direct sympathetic nerve stimulation and ß-adrenergic agonists we were able to characterize the effect myocardial infarction and chronic nicotine exposure have on sympathetic remodeling and hyperactivity. We evaluated the role that chondroitin sulfate proteoglycans (CSPG) have in sympathetic nerve hypo-innervation after myocardial infarction in the rabbit heart and the resulting electrophysiological consequences. We found that CSPGs are present in the hypoinnervated infarct region and that hypo-innervation results in changes in Ca2+ handling and alterations in cardiac electrophysiology; these results confirm previous rodent work. Additionally, we characterized the effect chronic nicotine has on Ca2+ mishandling, electrophysiological changes, and arrhythmia susceptibility. We found that 4 weeks of chronic nicotine exposure results in sympathetic hypo-innervation of the myocardium, diminished adrenergic responsiveness, and potentially detrimental sympathetic and electrophysiological remodeling. This dissertation provides a comprehensive perspective on how the effects of sympathetic remodeling and hyperactivity on cardiac electrophysiology in the rabbit heart.