Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation

Salavatian, Siamak; Beaumont, Éric; Longpré, Jean-Philippe; Armour, J. Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam; Ardell, Jeffrey L.

doi:10.1152/ajpheart.00443.2016

Cited by 50 publications

(34 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, 30 min of LLTS per day for 4 weeks normalized glucose levels in diabetic rats (Wang et al., ). Notably, the neural processing elements of the cardiac autonomic nervous system also demonstrate memory to VNS (Salavatian et al., ), which may also contribute to the cardioprotective effects of LLTS in our study. In the present study, short‐term, intermittent LLTS, delivered daily for 4 weeks significantly suppressed cardiac inflammation and fibrosis, attenuated BP elevation and improved LV hypertrophy and diastolic dysfunction in a rat model of HFpEF.…”

Section: Discussionsupporting

confidence: 64%

Low‐level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction

Zhou

Filiberti

Humphrey

et al. 2018

Experimental Physiology

View full text Add to dashboard Cite

Inflammation and fibrosis play a central role in the development of heart failure with preserved ejection fraction (HFpEF). We previously showed that low-level, transcutaneous stimulation of the vagus nerve at the tragus (LLTS) is anti-inflammatory. We investigated the effect of chronic intermittent LLTS on cardiac inflammation, fibrosis and diastolic dysfunction in a rat model of HFpEF. Dahl salt-sensitive (DS) rats were randomized in 3 groups: low salt (LS, 0.3% NaCl; n=12; control group without stimulation) and high salt (HS, 4% NaCl) with either active (n=18) or sham (n=18) LLTS at 7 weeks of age. After 6 weeks of diet (baseline), sham or active LLTS (20Hz, 2mA, 0.2ms) was implemented for 30 minutes daily for 4 weeks. Echocardiography was performed at baseline and 4 weeks after treatment (endpoint). At endpoint, left ventricle (LV) histology and gene expression were examined. After 6 weeks of diets, HS rats developed hypertension and LV hypertrophy compared to LS rats. At endpoint, LLTS significantly attenuated blood pressure elevation, prevented the deterioration of diastolic function and improved LV circumferential strain, compared to the HS sham group. LV inflammatory cell infiltration and fibrosis were attenuated in the HS active compared to the HS sham group. Pro-inflammatory and pro-fibrotic genes [tumor necrosis factor, osteopontin, interleukin (IL)-11, IL-18 and IL-23A] were differentially altered in the 2 groups. Chronic intermittent LLTS ameliorates diastolic dysfunction, and attenuates cardiac inflammation and fibrosis in a rat model of HFpEF, suggesting that LLTS may be used clinically as a novel noninvasive neuromodulation therapy in HFpEF.

show abstract

Section: Discussionsupporting

confidence: 64%

Low‐level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction

Zhou

Filiberti

Humphrey

et al. 2018

Experimental Physiology

View full text Add to dashboard Cite

show abstract

“…In addition to interacting with the stellate ganglion, VNS also targets convergent local circuit neurons of the intrinsic cardiac nervous system to mitigate the potential for neurally induced AF. 28 …”

Section: Discussionmentioning

confidence: 99%

Left cervical vagal nerve stimulation reduces skin sympathetic nerve activity in patients with drug resistant epilepsy

et al. 2017

View full text Add to dashboard Cite

Background We recently reported that the skin sympathetic nerve activity (SKNA) can be used to estimate the sympathetic tone in humans. In animal models, vagal nerve stimulation (VNS) can damage the stellate ganglion, reduce stellate ganglion nerve activity and suppress cardiac arrhythmia. Whether or not VNS can suppress sympathetic tone in humans remain unclear. Objective To test the hypothesis that VNS suppresses SKNA in patients with drug resistant epilepsy. Methods We used electrocardiogram (ECG) patch electrodes to continuously record SKNA in 26 patients with drug resistant epilepsy who were admitted for video electroencephalographic monitoring. Among them, 6 (2 men, age 40±11 years) were previously treated with VNS and 20 (7 men, age 37±8 years) did not. The signals from ECG leads I and II were filtered to detect SKNA. Results The VNS had an ON-time of 30 s and OFF-time of 158±72 s, with output of 1.92±0.42 mA at 24.17±2.01 Hz. The average SKNA (aSKNA) during VNS OFF-time was 1.06 μV [95% confidence interval, CI, 0.93 to 1.18] in lead I and 1.13 μV [CI, 0.99 to 1.27] in lead II, which was significantly lower than 1.38 μV [CI, 1.01 to 1.75, p=0.036] and 1.38 μV [CI, 0.98 to 1.78, p=0.035] of the control Group, respectively. The heart rate was 65 bpm [CI, 59 to 71] in VNS group, significantly lower than 77 bpm [95% CI, 71 to 83] in control group. Conclusion Patients with VNS had significantly lower SKNA than patients without VNS.

show abstract

“…; Salavatian et al . ) and in preservation of cardiac function in reduced (HFrEF) and preserved (HFpEF) heart failure (Sabbah et al . ; Shinlapawittayatorn et al .…”

Section: Introductionmentioning

confidence: 99%

Defining the neural fulcrum for chronic vagus nerve stimulation: implications for integrated cardiac control

Ardell¹,

Nier

Hammer³

et al. 2017

The Journal of Physiology

Self Cite

127

150

View full text Add to dashboard Cite

Vagus nerve stimulation (VNS) is an emerging therapy for treatment of chronic heart failure and remains a standard of therapy in patients with treatment-resistant epilepsy. The objective of this work was to characterize heart rate (HR) responses (HRRs) during the active phase of chronic VNS over a wide range of stimulation parameters in order to define optimal protocols for bidirectional bioelectronic control of the heart. In normal canines, bipolar electrodes were chronically implanted on the cervical vagosympathetic trunk bilaterally with anode cephalad to cathode (n = 8, 'cardiac' configuration) or with electrode positions reversed (n = 8, 'epilepsy' configuration). In awake state, HRRs were determined for each combination of pulse frequency (2-20 Hz), intensity (0-3.5 mA) and pulse widths (130-750 μs) over 14 months. At low intensities and higher frequency VNS, HR increased during the VNS active phase owing to afferent modulation of parasympathetic central drive. When functional effects of afferent and efferent fibre activation were balanced, a null HRR was evoked (defined as 'neural fulcrum') during which HRR ≈ 0. As intensity increased further, HR was reduced during the active phase of VNS. While qualitatively similar, VNS delivered in the epilepsy configuration resulted in more pronounced HR acceleration and reduced HR deceleration during VNS. At termination, under anaesthesia, transection of the vagi rostral to the stimulation site eliminated the augmenting response to VNS and enhanced the parasympathetic efferent-mediated suppressing effect on electrical and mechanical function of the heart. In conclusion, VNS activates central then peripheral aspects of the cardiac nervous system. VNS control over cardiac function is maintained during chronic therapy.

show abstract

Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation

Cited by 50 publications

References 76 publications

Low‐level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction

Low‐level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction

Left cervical vagal nerve stimulation reduces skin sympathetic nerve activity in patients with drug resistant epilepsy

Defining the neural fulcrum for chronic vagus nerve stimulation: implications for integrated cardiac control

Contact Info

Product

Resources

About