Special Issue "Autonomic Nervous System: From Bench to Bedside"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Neuroscience".

Deadline for manuscript submissions: 31 December 2019.

Special Issue Editor

Dr. Eleonora Tobaldini
E-Mail Website
Guest Editor
University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy
Interests: autonomic; heart rate variability; sleep

Special Issue Information

Dear Colleagues,

The pivotal role of the autonomic nervous system (ANS) in the pathogenesis and progression of cardiovascular diseases is well known. However, it has recently become evident that ANS is largely involved in the modulation of several other systems, such as the immune system and inflammation. This has lead to the hypothesis that ANS might represent a crucial interface between the environment, the central nervous system and the development of chronic non-communicable diseases.

The status of ANS is an independent prognostic factor for adverse cardiovascular outcomes and ANS has been recognized as a major determinant of health and prognosis. All conditions characterized by a greater sympathetic modulation are associated with a poor prognosis, while the predominant vagal control is linked to a better outcome. However, while the sympathetic nervous system can be easily targeted with drugs such as beta-blockers, the modulation of vagal activity has been extremely limited. Interestingly, considerable technological progress in the field of neuromodulation has made it possible to target ANS, which represents a new feasible frontier in clinical practice.

The aim of the present Special Issue is to collect reviews and original research articles that will provide updates and future perspectives about ANS in different clinical medicine settings.

Dr. Eleonora Tobaldini
Guest Editor

Manuscript Submission Information

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Keywords

  • Autonomic Nervous System
  • Sympathetic
  • Vagal
  • Neuromodulation
  • Cardiovascular Diseases
  • Sleep
  • Dysautonomia
  • Heart Rate Variability

Published Papers (10 papers)

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Research

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Open AccessArticle
The Association between Nutritional Markers and Heart Rate Variability Indices in Patients Undergoing Chronic Hemodialysis
J. Clin. Med. 2019, 8(10), 1700; https://doi.org/10.3390/jcm8101700 - 16 Oct 2019
Abstract
The associations between nutritional markers and heart rate variability (HRV) are poorly addressed. This study aimed to evaluate whether malnutrition is associated with the altered autonomic nervous system (ANS) function. This cross-sectional study was conducted enrolling 175 patients (100 women, mean age 65.1 [...] Read more.
The associations between nutritional markers and heart rate variability (HRV) are poorly addressed. This study aimed to evaluate whether malnutrition is associated with the altered autonomic nervous system (ANS) function. This cross-sectional study was conducted enrolling 175 patients (100 women, mean age 65.1 ± 12.9 years) receiving chronic hemodialysis in a teaching hospital from June to August 2010. We performed HRV measurements before and during the index hemodialysis and compared these HRV values between two groups categorized by the individual nutritional marker. By using the multivariate generalized estimating equation with adjustment, we exhibited the independent associations between HRV and poor nutritional status defined by serum albumin < 3.8 g/dL, total cholesterol < 100 mg/dL, body mass index < 23 kg/m2, bodyweight loss within six months > 10%, bodyweight loss within three months > 5%, and normalized protein catabolic rate < 1.1 g/kg BW/day. The current study disclosed ANS impairment in hemodialysis patients with poor nutritional status. The impaired ANS function might be a potential mechanism linking malnutrition to subsequent adverse prognoses in hemodialysis patients. Further investigations are warranted to confirm these findings and clarify the causal association among this complex issue. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Open AccessArticle
Determinants of Nocturnal Cardiovascular Variability and Heart Rate Arousal Response in Restless Legs Syndrome (RLS)/Periodic Limb Movements (PLMS)
J. Clin. Med. 2019, 8(10), 1619; https://doi.org/10.3390/jcm8101619 - 04 Oct 2019
Abstract
Recent studies have suggested that restless legs syndrome is associated with an increased prevalence of cardiovascular diseases mediated by sympathetic activation occurring during periodic limb movements. The aim of this study was to establish which factors affect the degree of sympathetic activation during [...] Read more.
Recent studies have suggested that restless legs syndrome is associated with an increased prevalence of cardiovascular diseases mediated by sympathetic activation occurring during periodic limb movements. The aim of this study was to establish which factors affect the degree of sympathetic activation during the basal condition and during periodic limb movements that may contribute to increased vascular risk. Fifty untreated restless legs syndrome patients aged 62.6 ± 11.1 y, free of cardiovascular diseases, were examined. Heart rate variability was calculated during wakefulness and all sleep stages, during periods with and without periodic limb movements. Heart rate changes before and after periodic limb movement onset were analyzed to assess the arousal response to periodic limb movements. Both analyses took into account the effects of age, gender, periodic limb movement duration, periodic limb movement index, periodic limb movement interval and periodicity, and magnitude of muscular activity (electromyogram power). Compared to periods without periodic limb movements, a significant increase in sympathetic activity occurred in periods with periodic limb movements, independent of age, sex and periodic limb movement characteristics. Data obtained from the cardiac arousal response to periodic limb movements showed that electromyogram power is the factor affecting sympathetic tonus. These results suggest that other factors, such as electromyogram power and individual susceptibility, should be considered in the assessment of the vascular risk related to restless legs syndrome. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Open AccessArticle
Cardiac and Vascular Sympathetic Baroreflex Control during Orthostatic Pre-Syncope
J. Clin. Med. 2019, 8(9), 1434; https://doi.org/10.3390/jcm8091434 - 10 Sep 2019
Abstract
We hypothesized that sympathetic baroreflex mediated uncoupling between neural sympathetic discharge pattern and arterial pressure (AP) fluctuations at 0.1 Hz during baroreceptor unloading might promote orthostatic pre-syncope. Ten volunteers (32 ± 6 years) underwent electrocardiogram, beat-to-beat AP, respiratory activity and muscle sympathetic nerve [...] Read more.
We hypothesized that sympathetic baroreflex mediated uncoupling between neural sympathetic discharge pattern and arterial pressure (AP) fluctuations at 0.1 Hz during baroreceptor unloading might promote orthostatic pre-syncope. Ten volunteers (32 ± 6 years) underwent electrocardiogram, beat-to-beat AP, respiratory activity and muscle sympathetic nerve activity (MSNA) recordings while supine (REST) and during 80° head-up tilt (HUT) followed by −10 mmHg stepwise increase of lower body negative pressure until pre-syncope. Cardiac and sympathetic baroreflex sensitivity were quantified. Spectrum analysis of systolic and diastolic AP (SAP and DAP) and calibrated MSNA (cMSNA) variability assessed the low frequency fluctuations (LF, ~0.1 Hz) of SAP, DAP and cMSNA variability. The squared coherence function (K2) quantified the coupling between cMSNA and DAP in the LF band. Analyses were performed while supine, during asymptomatic HUT (T1) and at pre-syncope onset (T2). During T2 we found that: (1) sympathetic baroreceptor modulation was virtually abolished compared to T1; (2) a progressive decrease in AP was accompanied by a persistent but chaotic sympathetic firing; (3) coupling between cMSNA and AP series at 0.1 Hz was reduced compared to T1. A negligible sympathetic baroreceptor modulation during pre-syncope might disrupt sympathetic discharge pattern impairing the capability of vessels to constrict and promote pre-syncope. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Open AccessArticle
LRRTM4 and PCSK5 Genetic Polymorphisms as Markers for Cognitive Impairment in A Hypotensive Aging Population: A Genome-Wide Association Study in Taiwan
J. Clin. Med. 2019, 8(8), 1124; https://doi.org/10.3390/jcm8081124 - 29 Jul 2019
Abstract
Hypotension can affect cerebral perfusion and worsen cognitive outcomes. The prevalence of low blood pressure (BP) rises with increasing age. To our knowledge, no study has examined the genetic biomarkers for hypotension-related cognitive impairment (CI) yet. Utilizing the population-based genome-wide study of the [...] Read more.
Hypotension can affect cerebral perfusion and worsen cognitive outcomes. The prevalence of low blood pressure (BP) rises with increasing age. To our knowledge, no study has examined the genetic biomarkers for hypotension-related cognitive impairment (CI) yet. Utilizing the population-based genome-wide study of the Taiwan Biobank containing the data of 2533 healthy aging subjects, we found after adjustments for age, sex, education years, and principal components at a suggestive level of 1 × 10−5 that minor alleles of leucine rich repeat transmembrane neuronal 4 (LRRTM4) (rs13388459, rs1075716, rs62171995, rs17406146, rs2077823, and rs62170897), proprotein convertase subtilisin/kexin type 5 (PCSK5) (rs10521467), and the intergenic variation rs117129097 (the nearby gene: TMEM132C) are risk factors for CI in hypotensive subjects. Except for rs117129097, these single nucleotide polymorphisms (SNPs) were not markers per se for CI or for BP regulation. However, we found a suggestive interaction effect between each of the eight SNPs and hypotension on CI risk. In the hypotensive participants, those carrying minor alleles were associated with a higher incidence of CI in an additive manner than were those carrying major alleles (2 × 10−4 to 9 × 10−7). Intensive BP lowering in elderly patients carrying a minor allele of the eight identified SNPs should raise cautions to prevent a potential treatment-induced neurodegeneration. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Open AccessArticle
Resting Heart Rate Variability Predicts Vulnerability to Pharmacologically-Induced Ventricular Arrhythmias in Male Rats
J. Clin. Med. 2019, 8(5), 655; https://doi.org/10.3390/jcm8050655 - 10 May 2019
Abstract
The electrical stability of the myocardium is dependent on the dynamic balance between sympathetic and parasympathetic influences on the heart, which is reflected by heart rate variability (HRV). Reduced HRV is a proposed predictor of sudden death caused by ventricular tachyarrhythmias in cardiac [...] Read more.
The electrical stability of the myocardium is dependent on the dynamic balance between sympathetic and parasympathetic influences on the heart, which is reflected by heart rate variability (HRV). Reduced HRV is a proposed predictor of sudden death caused by ventricular tachyarrhythmias in cardiac patients. However, the link between individual differences in HRV and ventricular tachyarrhythmic risk in populations without known pre-existing cardiac conditions is less well explored. In this study we investigated the extent to which individual differences in resting state HRV predict susceptibility to spontaneous and pharmacologically-induced ventricular arrhythmias in healthy rats. Radiotelemetric transmitters were implanted in 42 adult male Wild-type Groningen rats. ECG signals were recorded during 24-h resting conditions and under β-adrenoceptor pharmacological stimulation with isoproterenol and analyzed by means of time- and frequency-domain indexes of HRV. No significant association was found between individual differences in resting measures of HRV and spontaneous incidence of ventricular arrhythmias. However, lower resting values of HRV predicted a higher number of ventricular ectopic beats following β-adrenergic pharmacological stimulation with isoproterenol (0.02 mg/kg). Moreover, after isoproterenol administration, one rat with low resting HRV developed sustained ventricular tachycardia that led to death. The present results might be indicative of the potential utility of HRV measures of resting cardiac autonomic function for the prediction of ventricular arrhythmias, particularly during conditions of strong sympathetic activation, in populations without known cardiac disease. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Open AccessArticle
Relevance of Targeting the Distal Renal Artery and Branches with Radiofrequency Renal Denervation Approaches—A Secondary Analysis from a Hypertensive CKD Patient Cohort
J. Clin. Med. 2019, 8(5), 581; https://doi.org/10.3390/jcm8050581 - 27 Apr 2019
Abstract
We searched for an association between changes in blood pressure (BP) at 12 and 24 months after renal denervation (RDN) and the different patterns of ablation spots placement along the renal artery vasculature. We performed a post-hoc analysis of a 24-month follow-up evaluation [...] Read more.
We searched for an association between changes in blood pressure (BP) at 12 and 24 months after renal denervation (RDN) and the different patterns of ablation spots placement along the renal artery vasculature. We performed a post-hoc analysis of a 24-month follow-up evaluation of 30 patients who underwent RDN between 2011 and 2012 using our previous database. Patients who had (i) resistant hypertension, as meticulously described previously, and (ii) Chronic kidney disease (CKD) stages 2, 3 and 4. Correlations were assessed using the Pearson or Spearman correlation tests as appropriate. The mean change in systolic ambulatory BP monitoring (ABPM) compared to baseline was −19.4 ± 12.7 mmHg at the 12th (p < 0.0001) and −21.3 ± 14.1 mmHg at the 24th month (p < 0.0001). There was no correlation between the ABPM Systolic Blood Pressure (SBP)-lowering effect and the total number of ablated spots in renal arteries (17.7 ± 6.0) either at 12 (r = −0.3, p = 0.1542) or at 24 months (r = −0.2, p = 0.4009). However, correlations between systolic BP-lowering effect and the number of ablation spots performed in the distal segment and branches were significant at the 12 (r = −0.7, p < 0.0001) and 24 months (r = −0.8, p < 0.0001) follow-up. Our findings indicate a substantial correlation between the numbers of ablated sites in the distal segment and branches of renal arteries and the systolic BP-lowering effect in the long-term. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Open AccessArticle
Cardiac and Peripheral Autonomic Responses to Orthostatic Stress During Transcutaneous Vagus Nerve Stimulation in Healthy Subjects
J. Clin. Med. 2019, 8(4), 496; https://doi.org/10.3390/jcm8040496 - 11 Apr 2019
Abstract
Previous studies showed that transcutaneous vagus nerve stimulation (tVNS) modulates the autonomic nervous system (ANS) in resting condition. However, the autonomic regulation in response to an orthostatic challenge during tVNS in healthy subjects remains unknown. We tested the hypothesis that tVNS reduces heart [...] Read more.
Previous studies showed that transcutaneous vagus nerve stimulation (tVNS) modulates the autonomic nervous system (ANS) in resting condition. However, the autonomic regulation in response to an orthostatic challenge during tVNS in healthy subjects remains unknown. We tested the hypothesis that tVNS reduces heart rate (HR) and alters the responsivity of ANS to orthostatic stress in healthy subjects. In a randomized and cross-over trial, thirteen healthy subjects underwent two experimental sessions on different days: (1) tVNS and (2) control. Using a tVNS device, an auricular electrode was placed on the left cymba conchae of the external ear; an electric current with a pulse frequency of 25 Hz and amplitude between 1 and 6 mA was applied. For the assessment of ANS, the beat-to-beat HR and systolic arterial pressure (SAP) were analyzed using linear and nonlinear approaches during clinostatic and orthostatic conditions. In clinostatic conditions, tVNS reduced HR (p < 0.01), SAP variability (p < 0.01), and cardiac and peripheral sympathetic modulation (p < 0.01). The responsivity of the peripheral sympathetic modulation to orthostatic stress during tVNS was significantly higher when compared to the control session (p = 0.03). In conclusion, tVNS reduces the HR and affects cardiac and peripheral autonomic control and increases the responses of peripheral autonomic control to orthostatic stress in healthy subjects. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Open AccessArticle
Baroreceptor Sensitivity Predicts Functional Outcome and Complications after Acute Ischemic Stroke
J. Clin. Med. 2019, 8(3), 300; https://doi.org/10.3390/jcm8030300 - 03 Mar 2019
Abstract
Autonomic dysfunctions including impaired baroreflex sensitivity (BRS) can develop after acute ischemic stroke (AIS) and may predispose patients to subsequent cardiovascular adverse events and serve as potential indicators of long-term mortality. This study aimed to determine the potential short-term prognostic significance of BRS [...] Read more.
Autonomic dysfunctions including impaired baroreflex sensitivity (BRS) can develop after acute ischemic stroke (AIS) and may predispose patients to subsequent cardiovascular adverse events and serve as potential indicators of long-term mortality. This study aimed to determine the potential short-term prognostic significance of BRS after AIS. All patients admitted to Kaohsiung Veterans General Hospital within 72 h after onset of first-ever AIS between April 2008 and December 2012 were enrolled. Autonomic evaluation with continuous 10-minute monitoring of beat-to-beat hemodynamic and intracranial parameters was performed within 1 week after stroke by using the Task Force Monitor and transcranial Doppler. The 176 enrolled AIS patients were divided into high-BRS and low-BRS groups. All but two enrolled patients (who died within 3 months after stroke) attended scheduled follow-ups. The high-BRS group had significantly lower National Institutes of Health Stroke Scale (NIHSS) scores at 1 and 2 weeks after stroke and at discharge; lower modified Rankin scale (mRS) scores 1, 3, 6, and 12 months after stroke; and lower rates of complications and stroke recurrence compared to the low-BRS group. This study provides novel evidence of the utility of BRS to independently predict outcomes after AIS. Furthermore, modifying BRS may hold potential in future applications as a novel therapeutic strategy for acute stroke. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Open AccessArticle
Effects of a Short-Term Cycling Interval Session and Active Recovery on Non-Linear Dynamics of Cardiac Autonomic Activity in Endurance Trained Cyclists
J. Clin. Med. 2019, 8(2), 194; https://doi.org/10.3390/jcm8020194 - 06 Feb 2019
Cited by 3
Abstract
Measurement of the non-linear dynamics of physiologic variability in a heart rate time series (HRV) provides new opportunities to monitor cardiac autonomic activity during exercise and recovery periods. Using the Detrended Fluctuation Analysis (DFA) technique to assess correlation properties, the present study examines [...] Read more.
Measurement of the non-linear dynamics of physiologic variability in a heart rate time series (HRV) provides new opportunities to monitor cardiac autonomic activity during exercise and recovery periods. Using the Detrended Fluctuation Analysis (DFA) technique to assess correlation properties, the present study examines the influence of exercise intensity and recovery on total variability and complexity in the non-linear dynamics of HRV. Sixteen well-trained cyclists performed interval sessions with active recovery periods. During exercise, heart rate (HR) and beat-to-beat (RR)-intervals were recorded continuously. HRV time domain measurements and fractal correlation properties were analyzed using the short-term scaling exponent alpha1 of DFA. Lactate (La) levels and the rate of perceived exertion (RPE) were also recorded at regular time intervals. HR, La, and RPE showed increased values during the interval blocks (p < 0.05). In contrast, meanRR and DFA-alpha1 showed decreased values during the interval blocks (p < 0.05). Also, DFA-alpha1 increased to the level in the warm-up periods during active recovery (p < 0.05) and remained unchanged until the end of active recovery (p = 1.000). The present data verify a decrease in the overall variability, as well as a reduction in the complexity of the RR-interval-fluctuations, owing to increased organismic demands. The acute increase in DFA-alpha1 following intensity-based training stimuli in active recovery may be interpreted as a systematic reorganization of the organism with increased correlation properties in cardiac autonomic activity in endurance trained cyclists. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Review

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Open AccessReview
Heart Rate Variability in Sport Performance: Do Time of Day and Chronotype Play A Role?
J. Clin. Med. 2019, 8(5), 723; https://doi.org/10.3390/jcm8050723 - 21 May 2019
Cited by 1
Abstract
A reliable non-invasive method to assess autonomic nervous system activity involves the evaluation of the time course of heart rate variability (HRV). HRV may vary in accordance with the degree and duration of training, and the circadian fluctuation of this variable is crucial [...] Read more.
A reliable non-invasive method to assess autonomic nervous system activity involves the evaluation of the time course of heart rate variability (HRV). HRV may vary in accordance with the degree and duration of training, and the circadian fluctuation of this variable is crucial for human health since the heart adapts to the needs of different activity levels during sleep phases or in the daytime. In the present review, time-of-day and chronotype effect on HRV in response to acute sessions of physical activity are discussed. Results are sparse and controversial; however, it seems that evening-type subjects have a higher perturbation of the autonomic nervous system (ANS), with slowed vagal reactivation and higher heart rate values in response to morning exercise than morning types. Conversely, both chronotype categories showed similar ANS activity during evening physical tasks, suggesting that this time of day seems to perturb the HRV circadian rhythm to a lesser extent. The control for chronotype and time-of-day effect represents a key strategy for individual training schedules, and, in perspective, for primary injury prevention. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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