Sudden cardiac death (SCD) is a major cause of morbidity and mortality in patients with
coronary artery diseases and
myocardial infarction (MI). There is a circadian variation of the frequency of SCD. Beta-blocker
therapy significantly reduces the incidence of SCD after MI. These clinical observations suggest a close association between ventricular
arrhythmia and sympathetic activity in patients with MI. Following injury, peripheral nerves undergo
Wallerian degeneration, which may be followed by neurilemma cell proliferation and axonal regeneration (nerve sprouting), resulting in sympathetic hyperinnervation. It is possible that the increased innervation after myocardial injury may result in increased sympathetic nerve density, which in turn increases the propensity for
cardiac arrhythmia. While this Nerve Sprouting Hypothesis seemed to be intuitive, there was no experimental proof of a causal link between sympathetic nerve sprouting and arrhythmogenesis. We therefore performed several studies to determine the relationship between nerve sprouting and
cardiac arrhythmia. We also performed direct sympathetic nerve recording in an animal model of SCD. We found that cardiac sympathetic nerves are highly
plastic. In addition to MI and rapid pacing, nerve sprouting and heterogeneous sympathetic hyperinnervation may also be induced by
radiofrequency ablation,
hypercholesterolemia, and stem cells
transplantation. The coexistence of denervated and hyperinnervated area in the diseased myocardium could result in increased electrophysiological heterogeneity during sympathetic activation, leading to ventricular
arrhythmia and SCD.