Cardiovascular autonomic and hemodynamic responses to vagus nerve stimulation in drug-resistant epilepsy

Garamendi, Íñigo; Acera, Marian; Agundez, Marta; Galbarriatu, Lara; Marinas, Ainhoa; Pomposo, Iñigo; Valle, Elena Dalla; Palma, Jose‐Alberto; Gómez‐Esteban, Juan Carlos

doi:10.1016/j.seizure.2016.11.018

Cited by 26 publications

(15 citation statements)

References 30 publications

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“…The present study performed simultaneous assessment of heart rate variability using two independent Holter methods with short- and long-term ECG recordings, which both showed no difference in any of the measured frequency domains, pointing to the lack of effect of taVNS on cardiac autonomic function. In line with previous report showing no acute effect of vagal nerve stimulation on cardiovascular autonomic and hemodynamic parameters [39] , this study also did not observe alterations in BRS with taVNS ( Table 2 ). Of note, vagus nerve stimulation has been suggested to improve autonomic imbalance in heart failure patients [40] and chronically increases BRS and elevates HF power of HRV [41] , but, for this purpose, the stimulation parameters and dipole orientation are different from that used in epilepsy [39] and in the present study.…”

Section: Discussionsupporting

confidence: 93%

“…In line with previous report showing no acute effect of vagal nerve stimulation on cardiovascular autonomic and hemodynamic parameters [39] , this study also did not observe alterations in BRS with taVNS ( Table 2 ). Of note, vagus nerve stimulation has been suggested to improve autonomic imbalance in heart failure patients [40] and chronically increases BRS and elevates HF power of HRV [41] , but, for this purpose, the stimulation parameters and dipole orientation are different from that used in epilepsy [39] and in the present study. Whether other stimulation parameters or vagus stimulation techniques such as neck vagus stimulation with gammaCore ® [42] or VNS Therapy System implantation [20] , [21] , [39] , [40] will be able to affect the parasympathetic tone to the viscera and thereby might alter peripheral metabolism remains to be tested.…”

Section: Discussionsupporting

confidence: 93%

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Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism

Gancheva

Bierwagen

Markgraf

et al. 2018

Molecular Metabolism

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ObjectiveBrain insulin-induced improvement in glucose homeostasis has been proposed to be mediated by the parasympathetic nervous system. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) activating afferent branches of the vagus nerve may prevent hyperglycemia in diabetes models. We examined the effects of 14-min taVNS vs sham stimulation by Cerbomed Nemos® on glucose metabolism, lipids, and hepatic energy homeostasis in fasted healthy humans (n = 10, age 51 ± 6 yrs, BMI 25.5 ± 2.7 kg/m2).MethodsHeart rate variability (HRV), reflecting sympathetic and parasympathetic nerve activity, was measured before, during and after taVNS or sham stimulation. Endogenous glucose production was determined using [6,6-2H2]glucose, and hepatic concentrations of triglycerides (HCL), adenosine triphosphate (ATP), and inorganic phosphate (Pi) were quantified from 1H/31P magnetic resonance spectroscopy at baseline and for 180 min following stimulation.ResultstaVNS did not affect circulating glucose, free fatty acids, insulin, glucagon, or pancreatic polypeptide. Rates of endogenous glucose production (P = 0.79), hepatic HCL, ATP, and Pi were also not different (P = 0.91, P = 0.48 and P = 0.24) between taVNS or sham stimulation. Hepatic HCL, ATP, and Pi remained constant during prolonged fasting for 3 h. No changes in heart rate or shift in cardiac autonomic function from HRV towards sympathetic or parasympathetic predominance were detected.ConclusionNon-invasive vagus stimulation by Cerbomed Nemos® does not acutely modulate the autonomic tone to the visceral organs and thereby does not affect hepatic glucose and energy metabolism. This technique is therefore unable to mimic brain insulin-mediated effects on peripheral homeostasis in humans.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism

Gancheva

Bierwagen

Markgraf

et al. 2018

Molecular Metabolism

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“…From a clinical perspective, VNS-induced cardiac changes in epilepsy patients have been reported to be either rare or insignificant. However, activation of the brainstem through afferent pathways can variably alter both vagal and sympathetic cardiovascular modulations without significant hemodynamic effects in epilepsy (Garamendi et al, 2017). Nevertheless, cardiovascular effects of VNS using animal models have shown significant variability in response depending on the factors such as selected stimulation parameters and target nerve, as well as experimental condition (Ardell et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Vagus Nerve Stimulation Effects on Rat Cardiovascular and Immune Systems

et al. 2020

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Background: Investigations into the benefits of vagus nerve stimulation (VNS) through pre-clinical and clinical research have led to promising findings for treating several disorders. Despite proven effectiveness of VNS on conditions such as epilepsy and depression, understanding of off-target effects and contributing factors such as sex differences can be beneficial to optimize therapy design. New Methods: In this article, we assessed longitudinal effects of VNS on cardiovascular and immune systems, and studied potential sex differences using a rat model of longterm VNS. Rats were implanted with cuff electrodes around the left cervical vagus nerve for VNS, and wireless physiological monitoring devices for continuous monitoring of cardiovascular system using electrocardiogram (ECG) signals. ECG morphology and heart rate variability (HRV) features were extracted to assess cardiovascular changes resulting from VNS in short-term and long-term timescales. We also assessed VNS effects on expression of inflammatory cytokines in blood during the course of the experiment. Statistical analysis was performed to compare results between Treatment and Sham groups, and between male and female animals from Treatment and Sham groups. Results: Considerable differences between male and female rats in cardiovascular effects of VNS were observed in multiple cardiovascular features. However, the effects seemed to be transient with approximately 1-h recovery after VNS. While short-term cardiovascular effects were mainly observed in male rats, females in general showed more significant long-term effects even after VNS stopped. We did not observe notable changes or sex differences in systemic cytokine levels resulting from VNS. Comparison With Existing Methods: Compared to existing methods, our study design incorporated wireless physiological monitoring and systemic blood cytokine level analysis, along with long-term VNS experiments in unanesthetized rats to study sex differences. Conclusion: The contribution of sex differences for long-term VNS off-target effects on cardiovascular and immune systems was assessed using awake behaving rats. Although VNS did not change the concentration of inflammatory biomarkers in systemic circulation for male and female rats, we observed significant differences in cardiovascular effects of VNS characterized using ECG morphology and HRV analyses.

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“…Cardiac bradyarrhythmia represents a rare complication, few isolated cases during ongoing VNS therapy being reported [42, 43, 44, 45, 46]. VNS may also enhance sympathetic output, raising hippocampal noradrenaline levels [9, 47]. Locus coeruleus, the principal noradrenergic nucleus of the brain, is involved in the circuitry necessary for the anticonvulsant effectiveness of VNS [48].…”

Section: Discussionmentioning

confidence: 99%

“…VNS exerts through its diffuse projection via the nucleus of the solitary tract, or the reticular system, a cortical modulating effect, especially involving cerebral structures related to autonomic regulation, such as thalamus, amygdala or prefrontal region [8]. The impact of VNS on cardiovascular autonomic function in drug-resistant epilepsy patients remains a controversial subject and in need of further studies [9].…”

Section: Introductionmentioning

confidence: 99%

Heart rate variability and vagus nerve stimulation in epilepsy patients

Constantinescu¹,

Matei

Constantinescu

et al. 2019

Translational Neuroscience

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Background Vagus nerve stimulation (VNS) exerts a cortical modulating effect through its diffuse projections, especially involving cerebral structures related to autonomic regulation. The influence of VNS on cardiovascular autonomic function in drug-resistant epilepsy patients is still debated. We aimed to evaluate the impact of VNS on cardiovascular autonomic function in drug-resistant epilepsy patients, after three months of neurostimulation, using the heart rate variability (HRV) analysis. Methodology Multiple Trigonometric Regressive Spectral analysis enables a precise assessment of the autonomic control on the heart rate. We evaluated time and frequency-domain HRV parameters in resting condition and during sympathetic and parasympathetic activation tests in five epilepsy patients who underwent VNS procedure. Results We found appropriate cardiac autonomic responses to sympathetic and parasympathetic activation tests, described by RMSSD, pNN50, HF and LF/HF dynamics after three months of VNS. ON period of the neurostimulation may generate a transient vagal activation reflected on heart rate and RMSSD values, as observed in one of our cases. Conclusion VNS therapy in epilepsy patients seems not to disrupt the cardiac autonomic function. HRV represents a useful tool in evaluating autonomic activity. More extensive studies are needed to further explore cardiac autonomic response after neurostimulation.

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Cardiovascular autonomic and hemodynamic responses to vagus nerve stimulation in drug-resistant epilepsy

Cited by 26 publications

References 30 publications

Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism

Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism

Sex Differences in Vagus Nerve Stimulation Effects on Rat Cardiovascular and Immune Systems

Heart rate variability and vagus nerve stimulation in epilepsy patients

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