scholarly journals Reduced vagal tone in women with endometriosis and auricular vagus nerve stimulation as a potential therapeutic approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meihua Hao ◽  
Xishi Liu ◽  
Peijing Rong ◽  
Shaoyuan Li ◽  
Sun-Wei Guo
Keyword(s):  
Heart Rate ◽  
Vagus Nerve Stimulation ◽  
Therapeutic Potential ◽  
Vagal Tone ◽  
Sympathetic Nerves ◽  
Vagal Activity ◽  
Autonomic Balance ◽  
Vagus Nerves ◽  
Lesion Development

AbstractSensory and sympathetic nerves have been shown to promote the progression of endometriosis through the release of neuromediators and the lesional activation of respective receptors. The role of vagus nerves (VN) in lesional progression, however, is completely unclear, despite the signs suggestive of increased sympathetic tone in women with endometriosis. This study was undertaken to investigate whether VN plays any role in the progression of endometriosis. We recruited 45 patients with endometriosis and 42 healthy women, who were given electrocardiogram test and their heart rate variability was evaluated. In addition, three prospective, and randomized mouse experiments were conducted that evaluated, respectively, the effect of vagotomy, the effect of VN stimulation (VNS), and the therapeutic potential of VNS after the endometriosis was well established. All lesions were excised, weighed, and processed for immunohistochemistry and histochemistry analysis of select markers for lesional progression and fibrosis. We found that endometriosis patients exhibited reduced vagal activity as compared with controls, indicative of disrupted autonomic balance. Vagotomy increased while VNS decreased the lesion weight as compared with control mice, concomitant with more progressive and retarded lesion development and fibrogenesis, respectively. In addition, VNS demonstrated promising therapeutic effect, as evidenced by significantly reduced lesion weight, more attenuated lesional progression concomitant with improved hyperalgesia. Taken together, our data indicate that VN activity may play a dampening role in the progression of endometriosis. Consequently, boosting the VN activity may have therapeutic potentials for patients with endometriosis.

High Mobility Group Box-1 (HMGB1): A Potential Target in Therapeutics

2019 ◽  
Vol 20 (14) ◽  
pp. 1474-1485 ◽  
Author(s):  
Eyaldeva C. Vijayakumar ◽  
Lokesh Kumar Bhatt ◽  
Kedar S. Prabhavalkar
Keyword(s):  
Myocardial Infarction ◽  
Vagus Nerve Stimulation ◽  
Nuclear Protein ◽  
Therapeutic Potential ◽  
High Mobility ◽  
Dna Binding Protein ◽  
High Mobility Group ◽  
Eukaryotic Cells ◽  
Hmgb1 Protein

High mobility group box-1 (HMGB1) mainly belongs to the non-histone DNA-binding protein. It has been studied as a nuclear protein that is present in eukaryotic cells. From the HMG family, HMGB1 protein has been focused particularly for its pivotal role in several pathologies. HMGB-1 is considered as an essential facilitator in diseases such as sepsis, collagen disease, atherosclerosis, cancers, arthritis, acute lung injury, epilepsy, myocardial infarction, and local and systemic inflammation. Modulation of HMGB1 levels in the human body provides a way in the management of these diseases. Various strategies, such as HMGB1-receptor antagonists, inhibitors of its signalling pathway, antibodies, RNA inhibitors, vagus nerve stimulation etc. have been used to inhibit expression, release or activity of HMGB1. This review encompasses the role of HMGB1 in various pathologies and discusses its therapeutic potential in these pathologies.

scholarly journals Direct measurement of vagal tone in rats does not show correlation to HRV

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joseph T. Marmerstein ◽  
Grant A. McCallum ◽  
Dominique M. Durand
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Neural Activity ◽  
Vagal Tone ◽  
Neural Recording ◽  
The Body ◽  
Autonomic Nerve ◽  
Vagal Activity ◽  
Recording Technology

AbstractThe vagus nerve is the largest autonomic nerve, innervating nearly every organ in the body. “Vagal tone” is a clinical measure believed to indicate overall levels of vagal activity, but is measured indirectly through the heart rate variability (HRV). Abnormal HRV has been associated with many severe conditions such as diabetes, heart failure, and hypertension. However, vagal tone has never been directly measured, leading to disagreements in its interpretation and influencing the effectiveness of vagal therapies. Using custom carbon nanotube yarn electrodes, we were able to chronically record neural activity from the left cervical vagus in both anesthetized and non-anesthetized rats. Here we show that tonic vagal activity does not correlate with common HRV metrics with or without anesthesia. Although we found that average vagal activity is increased during inspiration compared to expiration, this respiratory-linked signal was not correlated with HRV either. These results represent a clear advance in neural recording technology but also point to the need for a re-interpretation of the link between HRV and “vagal tone”.

Renal denervation alters cardiovascular and endocrine responses to hemorrhage in conscious newborn lambs

1998 ◽  
Vol 275 (1) ◽  
pp. H285-H291 ◽  
Author(s):  
Francine G. Smith ◽  
Isam Abu-Amarah
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Renal Denervation ◽  
Plasma Renin ◽  
Sympathetic Nerves ◽  
Renal Nerves ◽  
Elevated Plasma ◽  
Baseline Levels ◽  
Renal Sympathetic

To investigate the role of renal sympathetic nerves in modulating cardiovascular and endocrine responses to hemorrhage early in life, we carried out three experiments in conscious, chronically instrumented lambs with intact renal nerves (intact; n = 8) and with bilateral renal denervation (denervated; n = 5). Measurements were made 1 h before and 1 h after 0, 10, and 20% hemorrhage. Blood pressure decreased transiently after 20% hemorrhage in intact lambs and returned to control levels. In denervated lambs, however, blood pressure remained decreased after 60 min. After 20% hemorrhage, heart rate increased from 170 ± 16 to 207 ± 18 beats/min in intact lambs but not in denervated lambs, in which basal heart rates were already elevated to 202 ± 21 beats/min. Despite an elevated plasma renin activity (PRA) measured in denervated (12.0 ± 6.4 ng ANG I ⋅ ml−1 ⋅ h−1) compared with intact lambs (4.0 ± 1.1 ng ANG I ⋅ ml−1 ⋅ h−1), the increase in PRA in response to 20% hemorrhage was similar in both groups. Plasma levels of arginine vasopressin increased from 11 ± 8 to 197 ± 246 pg/ml after 20% hemorrhage in intact lambs but remained unaltered in denervated lambs from baseline levels of 15 ± 10 pg/ml. These observations provide evidence that in the newborn, renal sympathetic nerves modulate cardiovascular and endocrine responses to hemorrhage.

scholarly journals Resting vagal activity in schizophrenia: Meta-analysis of heart rate variability as a potential endophenotype

2016 ◽  
Vol 208 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Annika Clamor ◽  
Tania M. Lincoln ◽  
Julian F. Thayer ◽  
Julian Koenig
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
High Frequency ◽  
Meta Analysis ◽  
Random Effect ◽  
Vagal Tone ◽  
Sensitivity Analyses ◽  
Psychotic Symptoms ◽  
Vagal Activity ◽  
Healthy Controls

BackgroundCardiac vagal tone, indexed by heart rate variability (HRV), is a proxy for the functional integrity of feedback mechanisms integrating central and peripheral physiology.AimsTo quantify differences in HRV in individuals with schizophrenia compared with healthy controls.MethodDatabases were systematically searched for studies eligible for inclusion. Random effect meta-analyses of standardised mean differences were calculated for vagal activity indicated by high-frequency HRV and the root mean square of successive R–R interval differences (RMSSD).ResultsThirty-four studies were included. Significant main effects were found for high-frequency HRV (P = 0.0008; Hedges' g =–0.98, 95% CI −1.56 to −0.41, k = 29) and RMSSD (P<0.0001; g =–0.91, 95% CI −1.19 to −0.62, k = 24), indicating lower vagal activity in individuals with schizophrenia than in healthy controls. Considerable heterogeneity was evident but effects were robust in subsequent sensitivity analyses.ConclusionsGiven the association between low HRV, threat processing, emotion regulation and executive functioning, reduced vagal tone may be an endophenotype for the development of psychotic symptoms.

scholarly journals An implant for long-term cervical vagus nerve stimulation in mice

2020 ◽  
Author(s):  
Ibrahim T. Mughrabi ◽  
Jordan Hickman ◽  
Naveen Jayaprakash ◽  
Eleni S. Papadoyannis ◽  
Adam Abbas ◽  
...  
Keyword(s):  
Heart Rate ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Therapeutic Potential ◽  
Therapeutic Implications ◽  
Wide Range ◽  
Heart Rate Threshold

AbstractVagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to treat a wide range of chronic conditions in which inflammation is implicated, including type 2 diabetes, obesity, atherosclerosis and heart failure. Many of these diseases have well-established mouse models but due to the significant surgical and engineering challenges that accompany a reliable interface for long-term VNS in mice, the therapeutic implications of this bioelectronic approach remain unexplored. Here, we describe a long-term VNS implant in mice, developed at 3 research laboratories and validated for between-lab reproducibility. Implant functionality was evaluated over 3-8 weeks in 81 anesthetized or conscious mice by determining the stimulus intensity required to elicit a change in heart rate (heart rate threshold, HRT). HRT was also used as a method to standardize stimulation dosing across animals. Overall, 60-90% of implants produced stimulus-evoked physiological responses for at least 4 weeks, with HRT values stabilizing after the second week of implantation. Furthermore, stimulation delivered through 6-week-old implants decreased TNF levels in a subset of mice with acute inflammation caused by endotoxemia. Histological examination of 4- to 6-week-old implants revealed fibrotic encapsulation and no gross fiber loss. This implantation and dosing approach provide a tool to systematically investigate the therapeutic potential of long-term VNS in chronic diseases modeled in the mouse, the most widely used vertebrate species in biomedical research.

Autonomic Balance in Cardiac Control

1958 ◽  
Vol 192 (3) ◽  
pp. 631-634 ◽  
Author(s):  
Robert F. Rushmer
Keyword(s):  
Heart Rate ◽  
Mechanical Performance ◽  
Stimulus Frequency ◽  
Sympathetic Nerves ◽  
Left Ventricular ◽  
Sympathetic Stimulation ◽  
Vagus Nerves ◽  
Ventricular Performance ◽  
Anesthetized Dogs ◽  
Stimulation Of

Stimulation of the sympathetic nerves to the heart in anesthetized dogs produced tachycardia and changes in left ventricular performance, including alterations in both pressures and dimensions. Stimulation of the vagus nerves in dogs predominately induced a bradycardia. When the heart rate was controlled by an artificial pacemaker, sympathetic stimulation produced changes in ventricular performance. By adjustments in stimulus frequency, the effects of vagal and sympathetic stimulation on heart rate could be balanced, but complete cancellation of effects was impossible because the vagus had a more powerful effect on heart rate and the sympathetic nerves had a greater influence on mechanical performance.

α2-Adrenergic modulation of colonic tone during hyperventilation

1997 ◽  
Vol 273 (5) ◽  
pp. G1135-G1140 ◽  
Author(s):  
Adil E. Bharucha ◽  
Vera Novak ◽  
Michael Camilleri ◽  
Alan R. Zinsmeister ◽  
Russell B. Hanson ◽  
...  
Keyword(s):  
Heart Rate ◽  
Sympathetic Activity ◽  
Wigner Distribution ◽  
Vagal Activity ◽  
Adrenergic Agents ◽  
Time Frequency ◽  
Adrenergic Modulation ◽  
Descending Colon ◽  
Time Frequency Mapping

Our aims were to assess the role of adrenergic modulation in the hyperventilation-induced increase in colonic tone. Of 40 healthy volunteers, 12 received placebo (saline) and the remaining 28 received either clonidine, yohimbine, phenylephrine, or ritodrine. Time-frequency mapping of heart rate based on Wigner distribution assessed variations in parasympathetic and sympathetic activity during hyperventilation. Tone in the descending colon was recorded by a barostat balloon before, during, and after 5 min of hyperventilation. Heart rate spectral analysis suggested diminished sympathetic and vagal activity during hyperventilation and increased sympathetic and vagal activity after hyperventilation. Adrenergic agents influenced ( P = 0.01) the tonic response after, but not during, hyperventilation. Yohimbine reduced the increment in colonic tone after hyperventilation compared with saline ( P < 0.05) and clonidine ( P = 0.002); phenylephrine and ritodrine had no effects. Different mechanisms modulate the increase in colonic tone during and after hyperventilation. Yohimbine attenuates the increase in colonic tone after hyperventilation probably by enhancing inhibitory sympathetic input to the colon.

Cardiac Vagal Tone and Stress

2021 ◽  
Author(s):  
Kevin T. Larkin ◽  
Alaina G. Tiani ◽  
Leah A. Brown
Keyword(s):  
Heart Rate ◽  
Psychiatric Disorders ◽  
Empirical Work ◽  
Vagal Tone ◽  
Vagal Nerve ◽  
Vagal Activity ◽  
Polyvagal Theory ◽  
Cardiac Vagal Tone ◽  
Parasympathetic Nerve ◽  
Cortical Regions

Based on its distinctive innervation between the brain and body, the vagal nerve has long been considered to play an important role in explaining how exposure to stress leads to numerous psychiatric disorders and cardiac diseases. In contrast to activation of the sympathetic nervous system during exposures to stress, the vagal nerve is responsible for parasympathetic regulation of visceral activity including cardiac functioning that often but not always co-occurs during periods of stress. Although methods exist to measure vagal nerve influences on the heart directly, most of the literature on both human and animal participants’ responses to stress employs the measurement of heart rate variability (HRV). HRV, the tendency for the heart rate to increase and decrease in adaptation to the changing physiological and external environment, can be easily detected using surface electrodes; several HRV parameters have been shown to be valid indicators of parasympathetic nerve activity. Theories of the evolutionary heritage of the vagal nerve, like Porges’ polyvagal theory and the subsequent neurovisceral integration perspective of Thayer and colleagues that traces the autonomic regulation of the heart into higher cortical regions, have served as important conceptual works to guide empirical work examining the effects of stress on both tonic and phasic vagal activity. A number of methodological approaches have been employed to evaluate whether exposure to stress affects vagal tone, including use of animal models, case-control samples of humans exposed to stressful living situations, and samples of humans diagnosed with a range of psychiatric disorders. Findings from studies comprising this literature support a relation between exposure to stress and reduced cardiac vagal tone. Both humans and animals typically exhibit reductions in daily HRV when exposed to a range of stressful situations or contexts. The relation between stress and phasic alterations in vagal functioning, the magnitude of the acute change in HRV in response to an acute stressor, is more complicated, likely involving significant moderating variables that have yet to be elucidated. In sum, considerable evidence supports an important neuroregulatory role of the vagal nerve in modulating the body’s response to environmental stress and potentially serving as an avenue for understanding how exposure to stress increases risk for psychiatric disorders as well as cardiovascular disease.

Autonomic cardiovascular control during submergence and emergence in bullfrogs

1979 ◽  
Vol 237 (3) ◽  
pp. R210-R216
Author(s):  
R. S. Lillo
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Vagal Tone ◽  
Systemic Blood Pressure ◽  
Vagal Activity ◽  
Adrenergic Blockade ◽  
Systemic Blood ◽  
Heart Rates ◽  
Heart Rate Decrease ◽  
Sympathetic Influence

Unanesthetized bullfrogs were involuntarily submerged for 25 min in air-saturated water at 21 degrees C. Significant bradycardia was observed while systemic blood pressure was maintained or slightly elevated. Upon emergence, heart rates immediately returned to presubmergence levels or higher. Similar responses were observed in frogs allowed to make voluntary dives in an experimental tank. Heart rates of vagal-blocked (atropine) frogs did not change during submergence or emergence. beta-Adrenergic blockade (propranolol) had little effect on the magnitude of heart rate decrease during submergence or its increase upon emergence. After alpha-adrenergic blockade (phentolamine), frogs developed diving bradycardia while undergoing a fall in systemic blood pressure. It is concluded that, in bullfrogs, 1) bradycardia during submergence is entirely due to increased vagal activity, 2) the immediate cardiac rate increase upon emergence apparently results from a decrease in vagal tone; and 3) there appears to be no substantial reciprocal sympathetic influence on heart rate during alterations in vagal tone.

scholarly journals Entropy in Heart Rate Dynamics Reflects How HRV-Biofeedback Training Improves Neurovisceral Complexity during Stress-Cognition Interactions

Entropy ◽  
2020 ◽  
Vol 22 (3) ◽  
pp. 317
Author(s):  
Veronique Deschodt-Arsac ◽  
Estelle Blons ◽  
Pierre Gilfriche ◽  
Beatrice Spiluttini ◽  
Laurent M. Arsac
Keyword(s):  
Heart Rate ◽  
Vagal Tone ◽  
Roc Curves ◽  
Biofeedback Training ◽  
Multiscale Entropy ◽  
Vagal Activity ◽  
System Complexity ◽  
Before And After ◽  
Signal Complexity ◽  
Additional Support

Despite considerable appeal, the growing appreciation of biosignals complexity reflects that system complexity needs additional support. A dynamically coordinated network of neurovisceral integration has been described that links prefrontal-subcortical inhibitory circuits to vagally-mediated heart rate variability. Chronic stress is known to alter network interactions by impairing amygdala functional connectivity. HRV-biofeedback training can counteract stress defects. We hypothesized the great value of an entropy-based approach of beat-to-beat biosignals to illustrate how HRVB training restores neurovisceral complexity, which should be reflected in signal complexity. In thirteen moderately-stressed participants, we obtained vagal tone markers and psychological indexes (state anxiety, cognitive workload, and Perceived Stress Scale) before and after five-weeks of daily HRVB training, at rest and during stressful cognitive tasking. Refined Composite Multiscale Entropy (RCMSE) was computed over short time scales as a marker of signal complexity. Heightened vagal tone at rest and during stressful tasking illustrates training benefits in the brain-to-heart circuitry. The entropy index reached the highest significance levels in both variance and ROC curves analyses. Restored vagal activity at rest correlated with gain in entropy. We conclude that HRVB training is efficient in restoring healthy neurovisceral complexity and stress defense, which is reflected in HRV signal complexity. The very mechanisms that are involved in system complexity remain to be elucidated, despite abundant literature existing on the role played by amygdala in brain interconnections.

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