The Effects of Sympathetic Nerve Stimulation on Ventricular Electrophysiology in Long QT Syndrome‐1

Abstract

Congenital long QT syndrome 1 (LQTS1) results from reduced slow activating delayed rectifier potassium channel (IKs) activity. Ventricular arrhythmias occur with increases in sympathetic tone which can cause sudden cardiac death (SCD). Underlying mechanisms are not understood but may include changes in electrical restitution (RT) – the relationship between action potential duration and diastolic interval. We aimed to examine the effects of sympathetic nerve stimulation (SNS) on effective refractory period (ERP), RT slope and inducibility of ventricular fibrillation (VF) in a pharmacological model of LQTS1. The innervated heart preparation from adult male guinea pigs (n=6, 450–550g) were used. ERP and LV apical and basal RT were measured using an extrastimulus protocol. Inducibility of VF was assessed with ventricular fibrillation threshold (VFT). Parameters were measured during baseline (BL) and SNS (3Hz, 1V) in control (Ctrl) and in the presence of the IKs blocker HMR1556 to mimic LQTS1 (HMR). Data are mean±SEM, analysed using Student's T‐Test (*vs BL, **vs Ctrl). During control, SNS significantly reduced ERP and VFT and increased RT slope but only at LV base, (Table). In the presence of HMR1556, the effects of SNS on ERP and VFT were augmented whilst the effect on RT was abolished. In conclusion, SNS increases susceptibility to VF which appears to be augmented in this pharmacological LQTS1 model and related to changes in ERP but not RT.Research support from the University of Leicester