Autonomic conflict exacerbates long QT associated ventricular arrhythmias

Autor: Winter, James, Tipton, Michael, Shattock, Michael J.
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Journal of Molecular and Cellular Cardiology
Winter, J, Tipton, M & Shattock, M J 2018, ' Autonomic conflict exacerbates long QT associated ventricular arrhythmias ', Journal of Molecular and Cellular Cardiology, vol. 116, pp. 145-154 . https://doi.org/10.1016/j.yjmcc.2018.02.001
ISSN: 1095-8584
0022-2828
DOI: 10.1016/j.yjmcc.2018.02.001
Popis: This study tested the hypothesis that concomitant sympathetic and parasympathetic stimulation (“autonomic conflict”) may act as a trigger for arrhythmias 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 arrhythmias 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 arrhythmias, as indicated by an increase in the average arrhythmias 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.
Highlights • Long QT syndrome associated arrhythmias were studied with dual autonomic stimulation. • EADs and TdP were triggered by increased vagal tone. • Sudden adrenergic stress increased the severity of observed arrhythmias. • Arrhythmias were prevented by sustained adrenergic stimulation. • The sequence of autonomic stimulation influences the severity of long QT arrhythmias.
Databáze: OpenAIRE