Sympathetic Nervous System Activity and Ventricular Tachyarrhythmias: Recent Advances

Authors


Address for reprints: Kelley P. Anderson, M.D., Department of Cardiology, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI 54449, USA. Tel: (715) 387-5301; Fax: (715) 389-4555; E-mail: kpand@att.net

Abstract

Sympathetic nervous system activity (SNSA) is believed to participate in the genesis of ventricular tachyarrhythmias (VTA) but understanding has been impeded by the number and complexity of effects and the paucity of data from humans. New information from studies of genetic disorders, animal models, and spontaneous human arrhythmias indicates the importance of the temporal pattern of SNSA in arrhythmia development. The proarrhythmic effects of short-term elevations of SNSA are exemplified by genetic disorders and include enhancement of early and delayed afterdepolarizations and increased dispersion of repolarization. The role of long-term elevations of SNSA is suggested by animal models of enhanced SNSA signaling that results in apoptosis, hypertrophy, and fibrosis, and sympathetic nerve sprouting caused by infusion of nerve growth factor. Processes that overlap short- and long-term effects are suggested by changes in R-R interval variability (RRV) that precede VTA in patients by several hours. SNSA-mediated alterations in gene expression of ion channels may account for some intermediate-term effects. The propensity for VTA is highest when short-, intermediate, and long-term changes are superimposed. Because the proarrhythmic effects are related to the duration and intensity of SNSA, normal regulatory processes such as parasympathetic activity that inhibits SNSA, and oscillations that continuously vary the intensity of SNSA may provide vital antiarrhythmic protection that is lost in severe heart failure and other disorders. These observations may have therapeutic implications. The recommended use of β-adrenergic receptor blockers to achieve a constant level of inhibition does not take into account the temporal patterns and regional heterogeneity of SNSA, the proarrhythmic effects of α-adrenergic receptor stimulation, or the potential proarrhythmic effects of β-adrenergic receptor blockade. Further research is needed to determine if other approaches to SNSA modulation can enhance the antiarrhythmic effects.

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