Background: Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether pre-emptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. Methods: 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 prior to and after pre-emptive right (RCV) vs left-sided (LCV) VNS (15 Hz, 500µsec; 1.2x bradycardia threshold). Results: Neuronal (n=89) activity at baseline (0.11±0.29Hz) increased during MNS-induced AF (0.51±1.30Hz; p<0.001). Convergent LCN's were preferentially activated by MNS. Pre-emptive RCV reduced MNS-induced changes in LCN activity (by 70%), while mitigating MNS-induced AF (by 75%). Pre-emptive 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 pre-emptive VNS. These anti-arrhythmic effects persisted post-VNS for, on average, 26 min. Conclusions: VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally-induced AF. The anti-arrhythmic properties imposed by VNS exhibit memory.
- atrial arrhythmia
- intrinsic cardiac nervous system
- stochastic neuronal interactivity
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology