TY - JOUR
T1 - Proarrhythmic proclivity of left-stellate ganglion stimulation in a canine model of drug-induced long-QT syndrome type 1
AU - ter Bekke, Rachel M. A.
AU - Moers, Annerie M. E.
AU - de Jong, Monique M. J.
AU - Johnson, Daniel M.
AU - Schwartz, Peter J.
AU - Vanoli, Emilio
AU - Volders, Paul G. A.
N1 - Funding Information:
P.G.A.V. was supported by a Vidi grant from the Netherlands Organization for Scientific Research ( ZonMw 91710365 ).
Funding Information:
P.G.A.V. was supported by a Vidi grant from the Netherlands Organization for Scientific Research (ZonMw 91710365).
Funding Information:
P.G.A.V. was supported by a Vidi grant from the Netherlands Organization for Scientific Research (ZonMw 91710365). The authors wish to thank Roel L.H.M.G. Sp?tjens BSc, Maastricht University Medical Center, The Netherlands for excellent graphical support, and Antonio Zaza, MD, University of Milano Bicocca, Italy for fruitful discussions on neurocardiac physiology.
Publisher Copyright:
© 2019 The Authors
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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 after depolarizations (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. (C) 2019 The Authors. Published by Elsevier B.V.
AB - 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 after depolarizations (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. (C) 2019 The Authors. Published by Elsevier B.V.
KW - Long-QT syndrome
KW - Ventricular arrhythmia
KW - Autonomic nervous system
KW - Torsades de pointes
KW - CARDIAC SYMPATHETIC DENERVATION
KW - TORSADES-DE-POINTES
KW - EARLY AFTERDEPOLARIZATIONS
KW - VENTRICULAR-FIBRILLATION
KW - ELECTROMECHANICAL WINDOW
KW - AUTONOMIC CONFLICT
KW - RISK
KW - REPOLARIZATION
KW - ARRHYTHMIA
KW - REFRACTORINESS
U2 - 10.1016/j.ijcard.2019.01.098
DO - 10.1016/j.ijcard.2019.01.098
M3 - Article
C2 - 30777408
SN - 0167-5273
VL - 286
SP - 66
EP - 72
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -