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Cardiovascular Autonomic Function: From Bench to Bedside

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A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: 30 June 2024 | Viewed by 16887

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Dr. Vera Geraldes

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Guest Editor

Assistant Professor, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
Interests: autonomic nervous system; cardiovascular diseases: neurogenic hypertension; cardiac autonomic modulation; heart rate variability; dysautonomia
Special Issues, Collections and Topics in MDPI journals

Dr. Isabel Rocha

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Guest Editor

Associate Professor, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
Interests: autonomic function; physiology; pathophysiology and evaluation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The autonomic nervous system (ANS) regulates involuntary physiological processes and is integral in controlling most organ systems of the body through a series of neural reflexes. It is also responsible for modulating and adapting the function of all organs to constantly changing external and internal conditions in order to maintain the body's homeostasis.

Dysfunctions of the autonomic nervous system are associated with the development of various diseases and are in the background of major, frequent, internal, and neurological conditions (such as diabetes, hypertension, and Parkinson's disease). Recently, neuromodulatory techniques have emerged as potential therapeutic approaches for the complete or partial treatment of autonomic disorders. In addition, ANS has been shown to be involved in the co-modulation of body functions, together with the immune system, the neuroendocrine system, and the inflammatory system. It thus forms an important interface between the central nervous system, the environment, and the development of chronic non-communicable diseases.

This Special Issue aims to collect reviews and original research articles that provide up-to-date information and future perspectives on various ANS areas of physiology and clinical medicine that affect all levels of autonomic function.

We are pleased to invite you to contribute to this Special Issue covering all aspects of the autonomic nervous system in humans and animals, including functional anatomy; physiology; pharmacology and therapeutics; behavioral aspects; neuromodulation; the dysfunction and ageing of autonomic neurons and their circuits; as well as the integrative role and emotional, physical, and motivational aspects of autonomic regulation.

We look forward to receiving your contributions.

Dr. Vera Geraldes
Dr. Isabel Rocha
Guest Editors

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Keywords

dysautonomia
heart rate variability
autonomic function testing
cardiovascular autonomic function
autonomic neuroscience
syncope
orthostatic hypotension
baroreflex

Published Papers (9 papers)

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Research

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24 pages, 17531 KiB

Open AccessArticle

CardioRVAR: A New R Package and Shiny Application for the Evaluation of Closed-Loop Cardiovascular Interactions

by Alvaro Chao-Écija, Manuel Víctor López-González and Marc Stefan Dawid-Milner

Biology 2023, 12(11), 1438; https://doi.org/10.3390/biology12111438 - 16 Nov 2023

Viewed by 905

Abstract

CardioRVAR is a new R package designed for the complete evaluation of closed-loop cardiovascular interactions and baroreflex sensitivity estimated from continuous non-invasive heart rate and blood pressure recordings. In this work, we highlight the importance of this software tool in the context of human cardiovascular and autonomic neurophysiology. A summary of the main algorithms that CardioRVAR uses are reviewed, and the workflow of this package is also discussed. We present the results obtained from this tool after its application in three clinical settings. These results support the potential clinical and scientific applications of this tool. The open-source tool can be downloaded from a public GitHub repository, as well as its specific Shiny application, CardioRVARapp. The open-source nature of the tool may benefit the future continuation of this work. Full article

(This article belongs to the Special Issue Cardiovascular Autonomic Function: From Bench to Bedside)

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17 pages, 2882 KiB

Open AccessArticle

Central Autonomic Network Regions and Hypertension: Unveiling Sympathetic Activation and Genetic Therapeutic Perspectives

by Vera Geraldes, Sérgio Laranjo, Catarina Nunes and Isabel Rocha

Biology 2023, 12(8), 1153; https://doi.org/10.3390/biology12081153 - 21 Aug 2023

Viewed by 1146

Abstract

Introduction: Hypertension, a leading cause of death, was investigated in this study to understand the role of specific brain regions in regulating blood pressure. The lateral parabrachial nucleus (LPBN), Kolliker-fuse nucleus (KF), and periductal grey matter (PAG) were examined for their involvement in hypertension. Methods: Lentiviral vectors were used to alter the activity of these brain regions in hypertensive rats. Over a 75-day period, blood pressure, heart rate, reflex responses, and heart rate variability were measured. Results: Decreasing the activity in the LPBN resulted in a reduced sympathetic outflow, lowering the blood pressure and heart rate. In the KF, the sympathetic activity decreased and chemoreflex variation was attenuated, without affecting the blood pressure. Silencing the PAG had no significant impact on blood pressure or sympathetic tone, but decreased cardiac baroreflex gain. Discussion: These findings highlight the significant role of the LPBN in hypertension-related sympathetic activation. Additionally, LPBN and KF neurons appear to activate mechanisms that control respiration and sympathetic outflow during chemoreceptor activation. Conclusions: The study provided insights into the contribution of the midbrain and pontine regions to neurogenic hypertension and offers potential avenues for future genetic interventions and developing novel treatment approaches. Full article

(This article belongs to the Special Issue Cardiovascular Autonomic Function: From Bench to Bedside)

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15 pages, 1240 KiB

Open AccessArticle

The Impact of Head-Up Tilt Sleeping on Orthostatic Tolerance: A Scoping Review

by Amber H. van der Stam, Sharon Shmuely, Nienke M. de Vries, Bastiaan R. Bloem and Roland D. Thijs

Biology 2023, 12(8), 1108; https://doi.org/10.3390/biology12081108 - 09 Aug 2023

Cited by 3 | Viewed by 1325

Abstract

To systematically summarize the evidence of head-up tilt sleeping (HUTS) on orthostatic tolerance, we conducted a systematic, predefined search in PubMed, OVID Embase, Cochrane and Web of Science. We included studies assessing the effect of HUTS on orthostatic tolerance and other cardiovascular measures and rated the quality with the American Academy of Neurology risk of bias tool. We included 10 studies (n = 185) in four groups: orthostatic hypotension (OH; 6 studies, n = 103), vasovagal syncope (1 study, n = 12), nocturnal angina pectoris (1 study, n = 10) and healthy subjects (2 studies, n = 58). HUTS duration varied (1 day–4 months) with variable inclinations (5°–15°). In two of six OH studies, HUTS significantly improved standing systolic blood pressure. Orthostatic tolerance was consistently enhanced in OH studies with higher angles (≥12°), in 2 out of 3 with smaller angles (5°) but also in one studying horizontal sleeping. In vasovagal syncope, HUTS significantly augmented resilience to extreme orthostatic stress. One study was rated as a class II risk of bias, one of Class II/III and eight of Class IV. The evidence favouring HUTS to improve orthostatic tolerance is weak due to variable interventions, populations, small samples and a high risk of bias. Despite this, we found some physiological signs suggesting a beneficial effect. Full article

(This article belongs to the Special Issue Cardiovascular Autonomic Function: From Bench to Bedside)

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13 pages, 1979 KiB

Open AccessArticle

Doxorubicin Dose-Dependent Impact on Physiological Balance—A Holistic Approach in a Rat Model

by Ana I. Afonso, Ângela Amaro-Leal, Filipa Machado, Isabel Rocha and Vera Geraldes

Biology 2023, 12(7), 1031; https://doi.org/10.3390/biology12071031 - 22 Jul 2023

Cited by 2 | Viewed by 1800

Abstract

Doxorubicin (DOX) is commonly used in several chemotherapies to treat various cancers, but it is known to cause cardiotoxicity and cardiac symptoms. Autonomic dysfunction is thought to contribute to the cardiotoxic effects of DOX, but the specific dose required to disrupt homeostatic processes is still unclear and is influenced by numerous factors. This study aimed to investigate how the DOX dosage affects autonomic function and physiological parameters, to elucidate the neurocardiac mechanisms underlying the observed cardiovascular side effects. Wistar rats were treated with DOX for four weeks and divided into three dosing groups: DOX8 (2 mg/kg/week), DOX16 (4 mg/kg/week), and DOX20 (5 mg/kg/week). A control group received NaCl 0.9% saline (1 mL/kg/week). In an acute experiment, we recorded blood pressure (BP), electrocardiogram, heart rate (HR), and respiratory rate (RF). Baroreflex gain and chemoreflex sensitivity were calculated, and cardiac tissue was analyzed with picrosirius histochemistry to measure collagen content. Our results showed that the LF/HF ratio, indicative of autonomic activity, was altered along with hypotension and bradycardia at a cumulative DOX dose threshold of 16 mg/kg. We observed a positive correlation between DOX dose and BP, HR, urinary norepinephrine, LF/HF ratio, and fibrotic heart area. Lower LF/HF ratios were associated with high DOX doses, reflecting drug-induced impairment of autonomic control of HR. This study provides valuable insights into the dose-dependent effects of DOX on physiological parameters and the development of cardiovascular dysfunction. These findings are critical, which is important for optimizing the management and therapeutic strategies for patients undergoing DOX-based chemotherapy. Full article

(This article belongs to the Special Issue Cardiovascular Autonomic Function: From Bench to Bedside)

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9 pages, 661 KiB

Open AccessCommunication

Decision-Making in Patients with Vasovagal Syncope: A Preliminary Study

by Muriel Méchenin and Jacques-Olivier Fortrat

Biology 2023, 12(7), 930; https://doi.org/10.3390/biology12070930 - 29 Jun 2023

Viewed by 859

Abstract

The aim of this study was to evaluate the differences in performance during a decisional conflict task between subjects with emotional/blood phobia and those with an orthostatic vasovagal syncope. A total of 332 young subjects were included, from which 99 were excluded because of their condition or treatment. The subjects were classified into four groups depending on their responses to a questionnaire: 98 in a control group, 10 in an emotional/blood phobia syncope group, 38 in an orthostatic syncope group, and 87 in an unclear status group. This former group was excluded. The subjects performed a decisional conflict task to quantify their conflict-management ability. The task was the computer version of the Simon Task. Emotional/blood phobia syncope subjects showed a delayed reaction time when faced with decisional conflict in comparison with the control and orthostatic syncope subjects (55.8 ± 17.7 ms, 20.5 ± 4.9 ms, and 13.4 ± 9.2 ms, respectively, p ≤ 0.05). Our result suggests that emotional/blood phobia and orthostatic syncope are two clinical entities. Decisions could be a target of management in patients with emotional/blood phobia syncope. The altered decision-making of subjects with emotion/blood phobia syncope emphasized the role of higher cerebral functions in blood pressure control. Full article

(This article belongs to the Special Issue Cardiovascular Autonomic Function: From Bench to Bedside)

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15 pages, 1799 KiB

Open AccessArticle

Imbalance of Peripheral Temperature, Sympathovagal, and Cytokine Profile in Long COVID

by Pablo Fabiano Moura das Neves, Juarez Antônio Simões Quaresma, Maria Alice Freitas Queiroz, Camilla Costa Silva, Enzo Varela Maia, João Sergio de Sousa Oliveira, Carla Manuela Almeida das Neves, Suellen da Silva Mendonça, Aline Semblano Carreira Falcão, Giovana Salomão Melo, Isabella Boechat Faria Santos, Jorge Rodrigues de Sousa, Eduardo José Melo dos Santos, Pedro Fernando da Costa Vasconcelos, Antonio Carlos Rosário Vallinoto and Luiz Fábio Magno Falcão

Biology 2023, 12(5), 749; https://doi.org/10.3390/biology12050749 - 19 May 2023

Cited by 1 | Viewed by 4696

Abstract

A persistent state of inflammation has been reported during the COVID-19 pandemic. This study aimed to assess short-term heart rate variability (HRV), peripheral body temperature, and serum cytokine levels in patients with long COVID. We evaluated 202 patients with long COVID symptoms categorized them according to the duration of their COVID symptoms (≤120 days, n = 81; >120 days, n = 121), in addition to 95 healthy individuals selected as controls. All HRV variables differed significantly between the control group and patients with long COVID in the ≤120 days group (p < 0.05), and participants in the long COVID ≤120 days group had higher temperatures than those in the long COVID >120 days group in all regions analysed (p < 0.05). Cytokine analysis showed higher levels of interleukin 17 (IL-17) and interleukin 2 (IL-2), and lower levels of interleukin 4 (IL-4) (p < 0.05). Our results suggest a reduction in parasympathetic activation during long COVID and an increase in body temperature due to possible endothelial damage caused by the maintenance of elevated levels of inflammatory mediators. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 appear to constitute a long-term profile of COVID-19 cytokines, and these markers are potential targets for long COVID-treatment and prevention strategies. Full article

(This article belongs to the Special Issue Cardiovascular Autonomic Function: From Bench to Bedside)

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13 pages, 741 KiB

Open AccessArticle

Effects of Different Fasting Interventions on Cardiac Autonomic Modulation in Healthy Individuals: A Secondary Outcome Analysis of the EDIF Trial

by Paul Zimmermann, Daniel Herz, Sebastian Karl, Johannes W. Weiß, Helmut K. Lackner, Maximilian P. Erlmann, Harald Sourij, Janis Schierbauer, Sandra Haupt, Felix Aberer, Nadine B. Wachsmuth and Othmar Moser

Biology 2023, 12(3), 372; https://doi.org/10.3390/biology12030372 - 26 Feb 2023

Viewed by 2241

Abstract

The impact of a fasting intervention on electrocardiographic (ECG) time intervals and heart rate variability (HRV) is a focus that is scarcely analyzed. The main focus of these secondary outcome data was to describe the impact of a different fasting intervention on ECG and HRV analyses. Twenty-seven healthy individuals participated in this study (11 females, aged 26.3 ± 3.8 years, BMI 24.7 ± 3.4 kg/m²), including a pre-intervention controlled run-in period. Participants were randomized to one of the three fasting cohorts: (I) alternate day fasting (ADF, n = 8), (II) 16/8 fasting (16/8 h of fasting/feasting, n = 11) and (III) 20/4 fasting (20/4 h of fasting/feasting, n = 8). An analysis of baseline ECG parameters and HRV parameters following different fasting interventions demonstrated the safety of these interventions without impacting on heart rate variability parameters during Schellong-1 testing, and revealed comparable preserved autonomic cardiac modulation (ACM) independently of the fasting intervention. In conclusion, different short-term fasting interventions demonstrated no safety ECG-based concerns and showed comparable ACM based on ECG and HRV assessments. Finally, our research topic might strengthen the scientific knowledge of intermittent fasting strategies and indicate potential clinically preventive approaches with respect to occurring metabolic disease and obesity in healthy young subjects. Full article

(This article belongs to the Special Issue Cardiovascular Autonomic Function: From Bench to Bedside)

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Review

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16 pages, 1449 KiB

Open AccessReview

Central Autonomic Mechanisms Involved in the Control of Laryngeal Activity and Vocalization

by Marta González-García, Laura Carrillo-Franco, Carmen Morales-Luque, Marc Stefan Dawid-Milner and Manuel Víctor López-González

Biology 2024, 13(2), 118; https://doi.org/10.3390/biology13020118 - 13 Feb 2024

Viewed by 1124

Abstract

In humans, speech is a complex process that requires the coordinated involvement of various components of the phonatory system, which are monitored by the central nervous system. The larynx in particular plays a crucial role, as it enables the vocal folds to meet and converts the exhaled air from our lungs into audible sounds. Voice production requires precise and sustained exhalation, which generates an air pressure/flow that creates the pressure in the glottis required for voice production. Voluntary vocal production begins in the laryngeal motor cortex (LMC), a structure found in all mammals, although the specific location in the cortex varies in humans. The LMC interfaces with various structures of the central autonomic network associated with cardiorespiratory regulation to allow the perfect coordination between breathing and vocalization. The main subcortical structure involved in this relationship is the mesencephalic periaqueductal grey matter (PAG). The PAG is the perfect link to the autonomic pontomedullary structures such as the parabrachial complex (PBc), the Kölliker–Fuse nucleus (KF), the nucleus tractus solitarius (NTS), and the nucleus retroambiguus (nRA), which modulate cardiovascular autonomic function activity in the vasomotor centers and respiratory activity at the level of the generators of the laryngeal-respiratory motor patterns that are essential for vocalization. These cores of autonomic structures are not only involved in the generation and modulation of cardiorespiratory responses to various stressors but also help to shape the cardiorespiratory motor patterns that are important for vocal production. Clinical studies show increased activity in the central circuits responsible for vocalization in certain speech disorders, such as spasmodic dysphonia because of laryngeal dystonia. Full article

(This article belongs to the Special Issue Cardiovascular Autonomic Function: From Bench to Bedside)

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28 pages, 2000 KiB

Open AccessReview

The Intrinsic Cardiac Nervous System: From Pathophysiology to Therapeutic Implications

by Giuseppe Giannino, Valentina Braia, Carola Griffith Brookles, Federico Giacobbe, Fabrizio D’Ascenzo, Filippo Angelini, Andrea Saglietto, Gaetano Maria De Ferrari and Veronica Dusi

Biology 2024, 13(2), 105; https://doi.org/10.3390/biology13020105 - 07 Feb 2024

Cited by 1 | Viewed by 1755

Abstract

The cardiac autonomic nervous system (CANS) plays a pivotal role in cardiac homeostasis as well as in cardiac pathology. The first level of cardiac autonomic control, the intrinsic cardiac nervous system (ICNS), is located within the epicardial fat pads and is physically organized in ganglionated plexi (GPs). The ICNS system does not only contain parasympathetic cardiac efferent neurons, as long believed, but also afferent neurons and local circuit neurons. Thanks to its high degree of connectivity, combined with neuronal plasticity and memory capacity, the ICNS allows for a beat-to-beat control of all cardiac functions and responses as well as integration with extracardiac and higher centers for longer-term cardiovascular reflexes. The present review provides a detailed overview of the current knowledge of the bidirectional connection between the ICNS and the most studied cardiac pathologies/conditions (myocardial infarction, heart failure, arrhythmias and heart transplant) and the potential therapeutic implications. Indeed, GP modulation with efferent activity inhibition, differently achieved, has been studied for atrial fibrillation and functional bradyarrhythmias, while GP modulation with efferent activity stimulation has been evaluated for myocardial infarction, heart failure and ventricular arrhythmias. Electrical therapy has the unique potential to allow for both kinds of ICNS modulation while preserving the anatomical integrity of the system. Full article

(This article belongs to the Special Issue Cardiovascular Autonomic Function: From Bench to Bedside)

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