New perspectives on the role of autonomic nervous system in the genesis of arrhythmias.
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.
Chen
Lan S
LS
Division of Neurology, Department of Pediatrics, Childrens Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA. lchen@chla.usc.edu
Zhou
Shengmei
S
Fishbein
Michael C
MC
Chen
Peng-Sheng
PS
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D015994:Incidence; D012307:Risk Factors; D015996:Survival Rate