Autonomic conflict exacerbates long QT associated ventricular arrhythmias

James Winter, Michael Tipton, Michael J. Shattock

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This study tested the hypothesis that concomitant sympathetic and parasympathetic stimulation (“autonomic conflict”) may act as a trigger for arrhythmia in long QT syndrome (LQTS). Studies were performed in isolated innervated rabbit hearts treated with clofilium (100 nmol/L); a potassium channel blocker. The influence of vagus nerve stimulation (VNS) on spontaneous ventricular arrhythmia was assessed in the absence/presence of sustained noradrenaline perfusion (100 nmol/L) and with sudden adrenergic stress (injections of noradrenaline into the perfusion line). Hearts were instrumented for a pseudo-electrocardiogram and monophasic action potential recordings. VNS, which slows heart rate, was associated with a stimulation frequency-dependent incidence of spontaneous early after-depolarisations (EADs) and ventricular tachycardia (VT), best predicted by the duration of the electrocardiographic T-wave and by triangulation of the ventricular action potential. In the presence of sustained (steady-state) noradrenaline perfusion, the incidence of EADs and VT with VNS was decreased from 73/55% to 45/27%, respectively. However, sudden adrenergic stress, imposed during periods of sustained VNS, was associated with a transient increase in the incidence of severity of observed arrhythmia, as indicated by an increase in the average arrhythmia score (1.6 ± 0.4 vs. 2.1 ± 0.7, p = .01). Analysis of electrophysiological parameters suggests that sudden adrenergic stress is associated with a transient prolongation, and increased triangulation, of the ventricular action potential, which may predispose to triggered activity. This study demonstrates that autonomic conflict is a pro-arrhythmic stimulus in LQTS. However, combined adrenergic and parasympathetic stimulation has a complex relationship with arrhythmogenicity, with differences in the effects of steady-state adrenergic activation vs. sudden adrenergic stress.
Original languageEnglish
Pages (from-to)145-154
JournalJournal of Molecular and Cellular Cardiology
Early online date2 Feb 2018
Publication statusPublished - 1 Mar 2018


  • autonomic conflict
  • long QT syndrome
  • torsades de pointes
  • sympathetic
  • parasympathetic
  • autonomic nervous system


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