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Failing Hearts Are More Vulnerable to Sympathetic, but not Vagal Stimulation Induced Atrial Fibrillation: Ameliorated with Dantrolene Treatment.

Research paper by Matthew S MS Delfiner, Colleen C Nofi, Ying Y Li, A Martin AM Gerdes, Youhua Y Zhang

Indexed on: 10 Jun '18Published on: 10 Jun '18Published in: Journal of Cardiac Failure



Abstract

Both vagal (VS) and sympathetic (SS) stimulations can increase atrial fibrillation (AF) inducibility, with VS being known as more arrhythmogenic in normal hearts. Heart failure (HF) results in autonomic dysfunction (characterized by sympathetic activation and vagal withdrawal) and is associated with an increased AF incidence. This study investigated whether failing hearts, compared to normal-controls, respond differently to autonomic stimulation induced AF arrhythmogenesis and the effect of dantrolene on SS enhanced AF in HF. A rat myocardial infarction (MI)-HF model was used. In experiment 1, AF inducibility was compared in 9 MI-HF rats versus 10 sham-control animals at baseline, during VS, and during SS with isoproterenol infusion. In experiment 2, dantrolene treatment (n=8) was compared with placebo-control (n=9) on SS induced AF inducibility in HF. Compared with sham-controls, baseline AF inducibility was higher in MI-HF group. AF inducibility was augmented in both groups by autonomic stimulation. However, under VS the increased magnitude was less in the MI-HF group (49±11% versus 80±10%, P=0.029), but was significantly more under SS (53±8% versus 6±7%, P<0.001), compared with sham-controls. Dantrolene significantly attenuated SS-enhanced AF in HF (69±6% versus 29±9%, P=0.006). Failing hearts are less sensitive to VS, but more vulnerable to SS induced AF compared to normal-controls. Dantrolene can significantly attenuate SS-enhanced AF in HF, indicating that cardiac ryanodine receptor dysfunction may play a critical role in SS-enhanced AF in HF and stabilizing leaky ryanodine receptor by dantrolene may be a new treatment option in this condition. Copyright © 2018 Elsevier Ltd. All rights reserved.