title: Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation.
abstract: Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory.
authors: Faculty of Medicine, Department of Physiology, Université de Montréal, Quebec, Canada.|Centre de Recherche, Hôpital du Sacré-Coeur, Montréal, Quebec, Canada.|Neurocardiology Research Center of Excellence, University of California Los Angeles, Los Angeles, California; and.
authors: Siamak
authors: S
authors: Salavatian
authors: Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee.
authors: Eric
authors: E
authors: Beaumont
authors: Faculty of Medicine, Department of Physiology, Université de Montréal, Quebec, Canada.|Centre de Recherche, Hôpital du Sacré-Coeur, Montréal, Quebec, Canada.
authors: Jean-Philippe
authors: JP
authors: Longpré
authors: Neurocardiology Research Center of Excellence, University of California Los Angeles, Los Angeles, California; and.|Cardiac Arrhythmia Center, University of California Los Angeles, Los Angeles, California.
authors: J Andrew
authors: JA
authors: Armour
authors: Faculty of Medicine, Department of Physiology, Université de Montréal, Quebec, Canada.|Centre de Recherche, Hôpital du Sacré-Coeur, Montréal, Quebec, Canada.
authors: Alain
authors: A
authors: Vinet
authors: Faculty of Medicine, Department of Physiology, Université de Montréal, Quebec, Canada.|Centre de Recherche, Hôpital du Sacré-Coeur, Montréal, Quebec, Canada.
authors: Vincent
authors: V
authors: Jacquemet
authors: Neurocardiology Research Center of Excellence, University of California Los Angeles, Los Angeles, California; and.|Cardiac Arrhythmia Center, University of California Los Angeles, Los Angeles, California.
authors: Kalyanam
authors: K
authors: Shivkumar
authors: Neurocardiology Research Center of Excellence, University of California Los Angeles, Los Angeles, California; and jardell@mednet.ucla.edu.|Cardiac Arrhythmia Center, University of California Los Angeles, Los Angeles, California.
authors: Jeffrey L
authors: JL
authors: Ardell
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D004285:Dogs; D006325:Heart Atria / Q000294:innervation*; D008482:Mediastinum / Q000294:innervation; D009206:Myocardium / Q000166:cytology*; D009415:Nerve Net; D009474:Neurons / Q000502:physiology*; D014630:Vagus Nerve; D055536:Vagus Nerve Stimulation
keywords: atrial arrhythmias; intrinsic cardiac nervous system; local circuit neurons; memory; stochastic neuronal interactivity; vagus