Proarrhythmic proclivity of left-stellate ganglion stimulation in a canine model of drug-induced long-QT syndrome type 1

ter Bekke, Rachel M. A.; Moers, Annerie M. E.; de Jong, Monique M. J.; Johnson, Daniel M.; Schwartz, Peter J.; Vanoli, Emilio and Volders, Paul G. A. (2019). Proarrhythmic proclivity of left-stellate ganglion stimulation in a canine model of drug-induced long-QT syndrome type 1. International Journal of Cardiology, 286 pp. 66–72.

DOI: https://doi.org/10.1016/j.ijcard.2019.01.098

Abstract

Background
Left-stellate ganglion stimulation (LSGS) can modify regional dispersion of ventricular refractoriness, promote triggered activity, and reduce the threshold for ventricular fibrillation (VF). Sympathetic hyperactivity precipitates torsades de pointes (TdP) and VF in susceptible patients with long-QT syndrome type 1 (LQT1). We investigated the electromechanical effects of LSGS in a canine model of drug-induced LQT1, gaining novel arrhythmogenic insights.

Methods
In nine mongrel dogs, the left and right stellate ganglia were exposed for electrical stimulation. ECG, left- and right-ventricular endocardial monophasic action potentials (MAPs) and pressures (LVP, RVP) were recorded. The electromechanical window (EMW; Q to LVP at 90% relaxation minus QT interval) was calculated. LQT1 was mimicked by infusion of the KCNQ1/I_Ks blocker HMR1556.

Results
At baseline, LSGS and right-stellate ganglion stimulation (RSGS) caused similar heart-rate acceleration and QT shortening. Positive inotropic and lusitropic effects were more pronounced under LSGS than RSGS. I_Ks blockade prolonged QTc, triggered MAP-early afterdepolarizations (EADs) and rendered the EMW negative, but no ventricular tachyarrhythmias occurred. Superimposed LSGS exaggerated EMW negativity and evoked TdP in 5/9 dogs within 30 s. Preceding extrasystoles originated mostly from the outflow-tracts region. TdP deteriorated into therapy-refractory VF in 4/5 animals. RSGS did not provoke TdP/VF.

Conclusions
In this model of drug-induced LQT1, LSGS readily induced TdP and VF during repolarization prolongation and MAP-EAD generation, but only if EMW turned from positive to very negative. We postulate that altered mechano-electric coupling can exaggerate regional dispersion of refractoriness and facilitates ventricular ectopy.

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