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 "Clinical Neurology".

Deadline for manuscript submissions: closed (31 December 2019).

Special Issue Editor

Prof. Dr. Eleonora Tobaldini
Website
Guest Editor
1. Department of Internal Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
2. Department of Clinical Sciences and Community Health, University of Milan, Italy
Interests: cardiovascular autonomic regulation; heart rate variability; sleep; vagal stimulation
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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

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Keywords

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

Published Papers (19 papers)

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Editorial

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Open AccessEditorial
Autonomic Nervous System: From Bench to Bedside
J. Clin. Med. 2020, 9(10), 3180; https://doi.org/10.3390/jcm9103180 - 30 Sep 2020
Abstract
In recent decades, new evidence has suggested that the role of the Autonomic Nervous System (ANS) is not marginal and not only limited to controlling vegetative functions [...] Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)

Research

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Open AccessArticle
Sympatho–Vagal Dysfunction in Patients with End-Stage Lung Disease Awaiting Lung Transplantation
J. Clin. Med. 2020, 9(4), 1146; https://doi.org/10.3390/jcm9041146 - 17 Apr 2020
Cited by 1
Abstract
Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage lung disease has not been studied yet. We investigated the effects of end-stage lung disease on [...] Read more.
Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage lung disease has not been studied yet. We investigated the effects of end-stage lung disease on CAC through the analysis of heart rate variability (HRV) among patients awaiting lung transplantation. Forty-nine patients on the waiting list for lung transplantation (LTx; 19 men, age 38 ± 15 years) and 49 healthy non-smoking controls (HC; 22 men, age 40 ± 16 years) were enrolled in a case–control study at Policlinico Hospital in Milan, Italy. LTx patients were divided into two groups, according to disease severity evaluated by the Lung Allocation Score (LAS). To assess CAC, electrocardiogram (ECG) and respiration were recorded at rest for 10 min in supine position and for 10 min during active standing. Spectral analysis identified low and high frequencies (LF, sympathetic, and HF, vagal). Symbolic analysis identified three patterns, i.e., 0V% (sympathetic) and 2UV% and 2LV% (vagal). Compared to HCs, LTx patients showed higher markers of sympathetic modulation and lower markers of vagal modulation. However, more severely affected LTx patients, compared to less severely affected ones, showed an autonomic profile characterized by loss of sympathetic modulation and predominant vagal modulation. This pattern can be due to a loss of sympathetic rhythmic oscillation and a subsequent prevalent respiratory modulation of heart rate in severely affected patients. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Open AccessArticle
Menstrual Cycle Changes in Vagally-Mediated Heart Rate Variability Are Associated with Progesterone: Evidence from Two Within-Person Studies
J. Clin. Med. 2020, 9(3), 617; https://doi.org/10.3390/jcm9030617 - 25 Feb 2020
Cited by 3
Abstract
A recent meta-analysis revealed that cardiac vagal activity (mostly indicated by vagally-mediated heart rate variability; HRV) decreases significantly from the follicular to luteal menstrual cycle phase in naturally-cycling participants. However, the question remains as to whether cyclical changes in estradiol (E2), progesterone (P4), [...] Read more.
A recent meta-analysis revealed that cardiac vagal activity (mostly indicated by vagally-mediated heart rate variability; HRV) decreases significantly from the follicular to luteal menstrual cycle phase in naturally-cycling participants. However, the question remains as to whether cyclical changes in estradiol (E2), progesterone (P4), or both are responsible for HRV fluctuations. We present the first studies to use repeated measures of E2, P4, and HRV across the cycle to model both the unique and interactive effects of person-centered E2 and P4 on HRV in multilevel models. In study one, 40 naturally-cycling participants were assessed weekly across four weeks, and were blind to the cycle focus of the study. In study two, 50 naturally-cycling participants were examined in three precisely defined cycle phases via ovulation testing. Both studies revealed that only P4 was correlated with HRV, such that higher-than-usual P4 significantly predicted lower-than-usual HRV within a given participant. In line with this, cycle phase comparisons revealed lower HRV in the mid-luteal phase (characterized by elevated P4) than in other phases. No significant main or interactive effects of E2 on HRV were found. Future female health studies should investigate individual differences in these effects and potential consequences of cyclical HRV changes on daily functioning. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
Open AccessArticle
Impact of Using Different Levels of Threshold-Based Artefact Correction on the Quantification of Heart Rate Variability in Three Independent Human Cohorts
J. Clin. Med. 2020, 9(2), 325; https://doi.org/10.3390/jcm9020325 - 23 Jan 2020
Cited by 4
Abstract
Heart rate variability (HRV) is a non-invasive indicator of autonomic nervous system function. HRV recordings show artefacts due to technical and/or biological issues. The Kubios software is one of the most used software to process HRV recordings, offering different levels of threshold-based artefact [...] Read more.
Heart rate variability (HRV) is a non-invasive indicator of autonomic nervous system function. HRV recordings show artefacts due to technical and/or biological issues. The Kubios software is one of the most used software to process HRV recordings, offering different levels of threshold-based artefact correction (i.e., Kubios filters). The aim of the study was to analyze the impact of different Kubios filters on the quantification of HRV derived parameters from short-term recordings in three independent human cohorts. A total of 312 participants were included: 107 children with overweight/obesity (10.0 ± 1.1 years, 58% men), 132 young adults (22.2 ± 2.2 years, 33% men) and 73 middle-aged adults (53.6 ± 5.2 years, 48% men). HRV was assessed using a heart rate monitor during 10–15 min, and the Kubios software was used for HRV data processing using all the Kubios filters available (i.e., 6). Repeated-measures analysis of variance indicated significant differences in HRV derived parameters in the time-domain (all p < 0.001) across the Kubios filters in all cohorts, moreover similar results were observed in the frequency-domain. When comparing two extreme Kubios filters, these statistical differences could be clinically relevant, e.g. more than 10 ms in the standard deviation of all normal R-R intervals (SDNN). In conclusion, the results of the present study suggest that the application of different Kubios filters had a significant impact on HRV derived parameters obtained from short-term recordings in both time and frequency-domains. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Open AccessArticle
First Evaluation of an Index of Low Vagally-Mediated Heart Rate Variability as a Marker of Health Risks in Human Adults: Proof of Concept
J. Clin. Med. 2019, 8(11), 1940; https://doi.org/10.3390/jcm8111940 - 11 Nov 2019
Cited by 7
Abstract
Multiple studies have demonstrated low vagally-mediated heart rate variability (HRV) being associated with a range of risk factors for heart disease and stroke, including inflammation, hyperglycemia, hyperlipidemia, and hypertension. Yet, no cut point exists that indicates elevated risk. In the present study we [...] Read more.
Multiple studies have demonstrated low vagally-mediated heart rate variability (HRV) being associated with a range of risk factors for heart disease and stroke, including inflammation, hyperglycemia, hyperlipidemia, and hypertension. Yet, no cut point exists that indicates elevated risk. In the present study we sought to identify a cut point-value for HRV that is associated with elevated risk across a range of known risk factors. Methods: A total of 9550 working adults from 19 study sites took part in a health assessment that included measures of inflammation, hyperglycemia, hyperlipidemia, and hypertension and vagally-mediated HRV (Root mean square of successive differences between normal heartbeats (RMSSD)). Multiple age and sex adjusted logistic regressions were calculated per risk factor (normal versus clinical range), with RMSSD being entered in binary at different cut points ranging from 15–39 msec with a 2 msec increment. Results: For daytime RMSSD, values below 25 ± 4 indicated elevated risk (odds ratios (OR) 1.5–3.5 across risk factors). For nighttime RMSSD, values below 29 ± 4 indicated elevated risk (OR 1.2–2.0). Conclusion: These results provide the first evidence that a single value of RMSSD may be associated with elevated risk across a range of established cardiovascular risk factors and may present an easy to assess novel marker of cardiovascular risk. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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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
Cited by 1
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
Cited by 2
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
Cited by 7
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
Cited by 2
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
Cited by 3
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
Cited by 3
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
Cited by 6
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
Cited by 2
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 9
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
Sleep Apnea, Hypertension and the Sympathetic Nervous System in the Adult Population
J. Clin. Med. 2020, 9(2), 591; https://doi.org/10.3390/jcm9020591 - 21 Feb 2020
Cited by 4
Abstract
Sleep apnea is very common in patients with cardiovascular disease, especially in patients with hypertension. Over the last few decades a number of discoveries have helped support a causal relationship between the two and even resistant hypertension. The role neurogenic mechanisms play has [...] Read more.
Sleep apnea is very common in patients with cardiovascular disease, especially in patients with hypertension. Over the last few decades a number of discoveries have helped support a causal relationship between the two and even resistant hypertension. The role neurogenic mechanisms play has gathered more attention in the recent past due to their immediate bedside utility. Several innovative discoveries in pathogenesis including those exploring the role of baroreflex gain, cardiovascular variability, chemoreceptor reflex activation and the sympathetic nervous system have emerged. In this review, we discuss the epidemiology of sleep apnea and hypertension and the pathogenic mechanisms contributing to neurogenic hypertension. Furthermore, recent management strategies in addition to continuous positive airway pressure (CPAP), such as upper airway stimulation and renal denervation that target these pathogenic mechanisms, are also discussed. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
Open AccessReview
Cardiovascular and Autonomic Responses to Energy Drinks—Clinical Implications
J. Clin. Med. 2020, 9(2), 431; https://doi.org/10.3390/jcm9020431 - 05 Feb 2020
Cited by 2
Abstract
There is an increasing consumption of energy drinks both in the United States and worldwide. The components of these beverages are sometimes unclear but commonly include caffeine, sugars, taurine, and B-vitamins. Young people, particularly those engaged in sports, studying, and in the military [...] Read more.
There is an increasing consumption of energy drinks both in the United States and worldwide. The components of these beverages are sometimes unclear but commonly include caffeine, sugars, taurine, and B-vitamins. Young people, particularly those engaged in sports, studying, and in the military are especially likely to be consumers of energy drinks. While limited data are available regarding their autonomic and hemodynamic effects, current literature suggests that energy drink consumption is accompanied by increases in blood pressure, sympathetic drive, and also in QT prolongation. There are no systematic long term studies identifying consequences of frequent energy drink consumption. However, multiple anecdotal reports implicate energy drinks in adverse cardiovascular events including atrial fibrillation, ventricular arrhythmia, myocardial infarction, and sudden death. Events such as atrial fibrillation may even occur in otherwise healthy subjects with structurally normal hearts. It is likely that these cardiovascular outcomes are triggered by the hemodynamic, autonomic, and electrocardiographic responses to energy drink consumption. What remains unclear is how concomitant use of other stimulants such as amphetamines and nicotine may interact to potentiate neural and circulatory responses and cardiovascular consequences when combined with energy drinks. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
Open AccessReview
Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies
J. Clin. Med. 2020, 9(2), 335; https://doi.org/10.3390/jcm9020335 - 24 Jan 2020
Cited by 7
Abstract
Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and prevalence of CAD in MS patients, as well as its association with MS type, disease characteristics, fatigue and immunotherapies used [...] Read more.
Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and prevalence of CAD in MS patients, as well as its association with MS type, disease characteristics, fatigue and immunotherapies used to treat MS. The analysis revealed that CAD is correlated with pathophysiological processes of MS, can trigger serious cardiovascular complications that may reduce life expectancy, and may have implications for treatment with immunotherapies, especially fingolimod. Numerous mainly small case–control or cohort studies have reported various measures of CAD (particularly heart rate variation) in MS patients, showing higher rates of abnormality versus controls. A smaller number of studies have reported on cardiac autonomic symptoms in MS, including orthostatic intolerance/dizziness in around 50% of patients. CAD also appears to be associated with disease duration and to be more common in progressive than relapsing–remitting MS. However, although a substantial evidence base suggests that assessing CAD in people with MS may be important, standardised methods to evaluate CAD in these patients have not yet been established. In addition, no studies have yet looked at whether treating CAD can reduce the burden of MS symptoms, disease activity or the rate of progression. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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Open AccessReview
A Systematic Review and Meta-Analysis of Within-Person Changes in Cardiac Vagal Activity across the Menstrual Cycle: Implications for Female Health and Future Studies
J. Clin. Med. 2019, 8(11), 1946; https://doi.org/10.3390/jcm8111946 - 12 Nov 2019
Cited by 11
Abstract
Interest in cardiac vagal activity (CVA; e.g., parasympathetically-mediated heart rate variability) as a biomarker of physical and mental health has increased exponentially in recent years. However, the understanding of sources of within-person change (i.e., intra-individual variance) in CVA is lagging behind. This systematic [...] Read more.
Interest in cardiac vagal activity (CVA; e.g., parasympathetically-mediated heart rate variability) as a biomarker of physical and mental health has increased exponentially in recent years. However, the understanding of sources of within-person change (i.e., intra-individual variance) in CVA is lagging behind. This systematic review and meta-analysis summarizes and quantifies current empirical evidence of within-person changes in measures of CVA across the menstrual cycle in naturally-cycling premenopausal females. We conducted an extensive literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement in five databases to identify observational studies with repeated measures of CVA in at least two menstrual cycle phases. A broad meta-analysis (nstudies = 37; nindividuals = 1,004) revealed a significant CVA decrease from the follicular to luteal phase (d = −0.39, 95% CI (−0.67, −0.11)). Furthermore, 21 studies allowed for finer-grained comparisons between each of two cycle phases (menstrual, mid-to-late follicular, ovulatory, early-to-mid luteal, and premenstrual). Significant decreases in CVA were observed from the menstrual to premenstrual (nstudies = 5; nindividuals = 200; d = −1.17, 95% CI (−2.18, −0.17)) and from the mid-to-late follicular to premenstrual phases (nstudies = 8; nindividuals = 280; d = −1.32, 95% CI (−2.35, −0.29)). In conclusion, meta-analyses indicate the presence of CVA fluctuations across the menstrual cycle. Future studies involving CVA should control for cycle phase. Recommendations for covarying or selecting cycle phase are provided. Full article
(This article belongs to the Special Issue Autonomic Nervous System: From Bench to Bedside)
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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 9
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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