Impact of Vagal Nerve Stimulation on Left Atrial Structure and Function in a Canine High-Rate Pacing Model

Abstract

Background Cervical vagal nerve stimulation (VNS) can improve left ventricular dysfunction in the setting of heart failure (HF). However, little is known about the impact of VNS on left atrial (LA) function. The aim of this study was to compare LA mechanics and histology between control and VNS-treated animals during HF development. Methods and Results Fifteen mongrel dogs were randomized into control (n=7) and VNS (n=8) groups. All dogs underwent 8 weeks of high-rate ventricular pacing (at 220bpm for the first 4 weeks to develop HF and another 4 weeks at 180bpm to maintain HF). LA contractile function (LA negative peak strain), conduit function (LA positive peak strain), and reservoir function (LA total strain) were measured from speckle tracking in two groups. At the end of the terminal study, the left atrial appendage was obtained. Baseline LA strains were comparable in the control and VNS treated dogs. At 4 and 8 weeks of ventricular pacing, all LA strains were decreased and LA volumes were increased in the control group compared with the VNS group (p <0.05). Histological evaluation of the LA revealed that percent fibrosis was significantly lower in the VNS vs. the control group (8±1% vs. 13±1%, p <0.001). Finally transmitral flow showed decreased atrial contribution to left ventricular filling in the control group (p <0.05). Conclusions VNS improved LA function and volumes and suppressed LA fibrosis in the canine high-rate ventricular pacing model. VNS is a novel and potentially useful therapy for improving LA function during HF.

Novel strategies and underlying protective mechanisms of modulation of vagal activity in cardiovascular diseases

“…The results showed that vagal stimulation markedly attenuated left ventricular dysfunction, prevented left ventricular dilation and positively influenced the apoptotic, inflammatory and NO biomarkers. Vagal stimulation therapy has also been shown to favourably affect the left atrial function and structure in heart failure dogs (Kusunose et al ., ). Our previous studies have suggested that vagal stimulation improved cardiac pump function, reduced infarct size and decreased serum myocardial enzyme activities in a rat model of acute myocardial infarction (Kong et al ., 2011; 2012a).…”

“…Vagal stimulation therapy has also been shown to favourably affect the left atrial function and structure in heart failure dogs (Kusunose et al, 2014). Our previous studies have suggested that vagal stimulation improved cardiac pump function, reduced infarct size and decreased serum myocardial enzyme activities in a rat model of acute myocardial infarction .…”

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control

“…VNS has also been investigated in animal models of chronic heart failure, a condition characterised by a sustained increase in sympathetic drive and a concurrent withdrawal of parasympathetic activity (Triposkiadis et al, 2009). A sustained improvement in cardiac function and heart failure symptoms has been demonstrated as a result of VNS (Hamann et al, 2013;Kusunose et al, 2014;Li et al, 2004;Sabbah et al, 2011;Zhang et al, 2009). …”

Role of the Autonomic Nervous System in Atrial Fibrillation

“…In addition to suppressing sympathetic outflow, vagal nerve and epicardial ganglionated plexi stimulations may be anti-inflammatory 100, 143, 144 and may improve LA function and suppress the development of LA fibrosis. 145 Renal sympathetic denervation may control AF through modification of the atrial substrates. 6 These findings suggest that neuromodulation may achieve its therapeutic effects in part by causing beneficial structural and functional remodeling in the heart.…”