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Integrative Effects and Vagal Mechanisms of Transcutaneous Electrical Acustimulation on Gastroesophageal Motility in Patients With Gastroesophageal Reflux Disease.
Zhang, B, Hu, Y, Shi, X, Li, W, Zeng, X, Liu, F, Chen, JDZ, Xie, WF
The American journal of gastroenterology. 2021;(7):1495-1505
Abstract
INTRODUCTION Impaired esophageal and gastric motilities are known to contribute to symptoms of gastroesophageal reflux disease (GERD). However, there is a lack of GERD therapy, targeting both gastric and esophageal functions. This study was designed to investigate the effects of transcutaneous electrical acustimulation (TEA) on symptoms of GERD and gastroesophageal functions and possible mechanisms in patients with GERD. METHODS Thirty patients with GERD with ineffective esophageal motility were equally divided and randomized into a 4-week sham-TEA or 4-week TEA treatment. The GERD questionnaire (GerdQ), GERD health-related quality-of-life questionnaire, high-resolution esophageal manometry, a nutrient drink test, the electrogastrogram, and ECG were performed to assess the severity of reflux symptoms, low esophageal sphincter (LES) pressure, distal contractile integral (DCI), gastric accommodation, gastric slow waves (GSW), and autonomic functions, respectively. RESULTS Compared with sham-TEA, the 4-week TEA treatment significantly decreased the GerdQ score (P = 0.011) and GERD health-related quality of life (P = 0.028) and improved nutrient drink-induced fullness (P < 0.001) and belching (P < 0.001) in patients with GERD. Although only acute TEA significantly enhanced LES pressure (P < 0.05), both acute and chronic TEA remarkedly increased DCI (P < 0.05) and reduced the incidence of ineffective esophageal contractions during wet swallows (P = 0.02). In addition, chronic TEA significantly increased gastric accommodation and the percentage of postprandial normal GSW compared with sham-TEA and baseline. Concurrently, TEA-enhanced vagal activity (P = 0.02) and the vagal activity positively correlated with LES pressure (r = 0.528; P = 0.003) and DCI (r = 0.522; P = 0.003). DISCUSSION The TEA treatment performed in this study improves reflux-related symptoms, increases DCI, reduces the incidence of ineffective esophageal contractions during wet swallows, and improves gastric accommodation and slow waves. The improvement in GERD symptoms might be attributed to the integrative effects of TEA on these gastroesophageal functions mediated via the vagal mechanism.
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Vagal reactivation after a cardiac rehabilitation session associated with hydration in coronary artery disease patients: crossover clinical trial.
Laurino, MJL, da Silva, AKF, Santos, LA, Ribeiro, F, Vanzella, LM, Corazza, DAG, Vanderlei, LCM
Scientific reports. 2021;(1):10482
Abstract
This study aimed to investigate the hydration influence on the autonomic responses of coronary artery disease subjects in the immediate recovery period after a cardiovascular rehabilitation session, in view of the risks of a delayed autonomic recovery for this population. 28 males with coronary artery disease were submitted to: (I) Maximum effort test; (II) Control protocol (CP), composed by initial rest, warm-up, exercise and passive recovery; (III) Hydration protocol (HP) similar to CP, but with rehydration during exercise. The recovery was evaluated through the heart rate (HR) variability, HR recovery and by the rate of perceived exertion and recovery. The main results revealed that the vagal reactivation occurred at the first 30 s of recovery in HP and after the first minute in CP. A better behavior of the HR at the first minute of recovery was observed in HP. The rate of perceived exertion had a significant decrease in the first minute of recovery in HP, while in CP this occurred after the third minute. In conclusion, despite an anticipated vagal reactivation found at HP, these results should be analyzed with caution as there were no significant differences between protocols for all variables and the effect sizes were small.
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Impaired Vagal Efficiency Predicts Auricular Neurostimulation Response in Adolescent Functional Abdominal Pain Disorders.
Kovacic, K, Kolacz, J, Lewis, GF, Porges, SW
The American journal of gastroenterology. 2020;(9):1534-1538
Abstract
INTRODUCTION To determine whether pretreatment vagal efficiency (VE), respiratory sinus arrhythmia, and heart period can predict pain improvement with auricular neurostimulation in pediatric functional abdominal pain disorders. METHODS A total of 92 adolescents with functional abdominal pain disorders underwent a 4-week randomized, double-blinded, sham-controlled auricular neurostimulation trial. Electrocardiogram-derived variables at baseline were used to predict pain using mixed effects modeling. RESULTS A 3-way interaction (95% confidence intervals: 0.004-0.494) showed that the treatment group subjects with low baseline VE had lower pain scores at week 3. There was no substantial change in the placebo or high VE treatment group subjects. This effect was supported by a significant correlation between baseline VE and degree of pain reduction only in the treatment group. DISCUSSION Impaired cardiac vagal regulation measured by VE predicts pain improvement with auricular neurostimulation.
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A 12-month pilot study outcomes of vagus nerve stimulation in Crohn's disease.
Sinniger, V, Pellissier, S, Fauvelle, F, Trocmé, C, Hoffmann, D, Vercueil, L, Cracowski, JL, David, O, Bonaz, B
Neurogastroenterology and motility. 2020;(10):e13911
Abstract
BACKGROUND The vagus nerve has anti-inflammatory properties. We aimed to investigate vagus nerve stimulation (VNS) as a new therapeutic strategy targeting an intrinsic anti-inflammatory pathway in a pilot study in Crohn's disease patients. The main objectives addressed the questions of long-term safety, tolerability, and anti-inflammatory effects of this therapy. This study is the continuation of previous reported findings at 6 months. METHODS Nine patients with moderate active disease underwent VNS. An electrode wrapped around the left cervical vagus nerve was continuously stimulated over 1 year. Clinical, biological, endoscopic parameters, cytokines (plasma, gut), and mucosal metabolites were followed-up. KEY RESULTS After 1 year of VNS, five patients were in clinical remission and six in endoscopic remission. C-reactive protein (CRP) and fecal calprotectin decreased in six and five patients, respectively. Seven patients restored their vagal tone and decreased their digestive pain score. The patients' cytokinergic profile evolved toward a more "healthy profile": Interleukins 6, 23, 12, tumor necrosis factor α, and transforming growth factorβ1 were the most impacted cytokines. Correlations were observed between CRP and tumor necrosis factor α, and some gut mucosa metabolites as taurine, lactate, alanine, and beta-hydroxybutyrate. VNS was well tolerated. CONCLUSION & INFERENCES Vagus nerve stimulation appears as an innovative and well-tolerated treatment in moderate Crohn's disease. After 12 months, VNS has restored a homeostatic vagal tone and reduced the inflammatory state of the patients. VNS has probably a global modulatory effect on the immune system along with gut metabolic regulations. This pilot study needs replication in a larger randomized double-blinded control study.
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Traumatic stress and the autonomic brain-gut connection in development: Polyvagal Theory as an integrative framework for psychosocial and gastrointestinal pathology.
Kolacz, J, Kovacic, KK, Porges, SW
Developmental psychobiology. 2019;(5):796-809
Abstract
A range of psychiatric disorders such as anxiety, depression, and post-traumatic stress disorder frequently co-occur with functional gastrointestinal (GI) disorders. Risk of these pathologies is particularly high in those with a history of trauma, abuse, and chronic stress. These scientific findings and rising awareness within the healthcare profession give rise to a need for an integrative framework to understand the developmental mechanisms that give rise to these observations. In this paper, we introduce a plausible explanatory framework, based on the Polyvagal Theory (Porges, Psychophysiology, 32, 301-318, 1995; Porges, International Journal of Psychophysiology, 42, 123-146, 2001; Porges, Biological Psychology, 74, 116-143, 2007), which describes how evolution impacted the structure and function of the autonomic nervous system (ANS). The Polyvagal Theory provides organizing principles for understanding the development of adaptive diversity in homeostatic, threat-response, and psychosocial functions that contribute to pathology. Using these principles, we outline possible mechanisms that promote and maintain socioemotional and GI dysfunction and review their implications for therapeutic targets.
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Inorganic nitrate supplementation attenuates peripheral chemoreflex sensitivity but does not improve cardiovagal baroreflex sensitivity in older adults.
Bock, JM, Ueda, K, Schneider, AC, Hughes, WE, Limberg, JK, Bryan, NS, Casey, DP
American journal of physiology. Heart and circulatory physiology. 2018;(1):H45-H51
Abstract
Aging is associated with increased peripheral chemoreceptor activity, reduced nitric oxide (NO) bioavailability, and attenuation of cardiovagal baroreflex sensitivity (BRS), collectively increasing the risk of cardiovascular disease. Evidence suggests that NO may attenuate peripheral chemoreflex sensitivity and increase BRS. Exogenous inorganic nitrate ([Formula: see text]) increases NO bioavailability via the [Formula: see text]-[Formula: see text]-NO pathway. Our hypothesis was that inorganic [Formula: see text] supplementation would attenuate peripheral chemoreflex sensitivity and enhance spontaneous cardiovagal BRS in older adults. We used a randomized, placebo-controlled crossover design in which 13 older (67 ± 3 yr old) adults ingested beetroot powder containing (BRA) or devoid of (BRP) [Formula: see text] and [Formula: see text] daily over 4 wk. Spontaneous cardiovagal BRS was assessed over 15 min of rest and was quantified using the sequence method. Chemoreflex sensitivity was assessed via ~5 min of hypoxia (10% fraction of inspired O2) and reported as the slope of the relationship between O2 saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BRA (from -0.14 ± 0.04 to -0.05 ± 0.02 l·min-1·%[Formula: see text]-1, P = 0.01) versus BRP (from -0.10 ± 0.05 to -0.11 ± 0.05 l·min-1·%[Formula: see text]-1, P = 0.80), with no differences in heart rate responsiveness (BRA: from -0.47 ± 0.06 to -0.33 ± 0.04 beats·min-1·%[Formula: see text]-1, BRP: from -0.48 ± 0.07 to -0.42 ± 0.06 beats·min-1·%[Formula: see text]-1) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BRA and BRP (interaction effects, P = 0.69, 0.94, and 0.39 for all, up, and down sequences, respectively), despite a reduction in resting systolic and mean arterial blood pressure in the experimental (BRA) group ( P < 0.01 for both). These findings illustrate that inorganic [Formula: see text] supplementation attenuates peripheral chemoreflex sensitivity without concomitant change in spontaneous cardiovagal BRS in older adults. NEW & NOTEWORTHY Exogenous inorganic nitrate supplementation attenuates ventilatory, but not heart rate, responsiveness to abbreviated hypoxic exposure in older adults. Additionally, inorganic nitrate reduces systolic and mean arterial blood pressure without affecting spontaneous cardiovagal baroreflex sensitivity. These findings suggest that inorganic nitrate may attenuate sympathetically oriented pathologies associated with aging.
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Novel transmitters in brain stem vagal neurocircuitry: new players on the pitch.
Bülbül, M, Travagli, RA
American journal of physiology. Gastrointestinal and liver physiology. 2018;(1):G20-G26
Abstract
The last few decades have seen a major increase in the number of neurotransmitters and neuropeptides recognized as playing a role in brain stem neurocircuits, including those involved in homeostatic functions such as stress responsiveness, gastrointestinal motility, feeding, and/or arousal/wakefulness. This minireview will focus on the known physiological role of three of these novel neuropeptides, i.e., apelin, nesfatin-1, and neuropeptide-S, with a special emphasis on their hypothetical roles in vagal signaling related to gastrointestinal motor functions.
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Alterations in dietary sodium intake affect cardiovagal baroreflex sensitivity.
Babcock, MC, Brian, MS, Watso, JC, Edwards, DG, Stocker, SD, Wenner, MM, Farquhar, WB
American journal of physiology. Regulatory, integrative and comparative physiology. 2018;(4):R688-R695
Abstract
High dietary sodium intake has been linked to alterations in neurally mediated cardiovascular function, but the effects of high sodium on cardiovagal baroreflex sensitivity (cBRS) in healthy adults are unknown. The purpose of this study was to determine whether high dietary sodium alters cBRS and heart rate variability (HRV) and whether acute intravenous sodium loading similarly alters cBRS and HRV. High dietary sodium (300 mmol/day, 7 days) was compared with low dietary sodium (20 mmol/day, 7 days; randomized) in 14 participants (38 ± 4 yr old, 23 ± 1 kg/m2 body mass index, 7 women). Acute sodium loading was achieved via a 23-min intravenous hypertonic saline infusion (HSI) in 14 participants (22 ± 1 yr old, 23 ± 1 kg/m2 body mass index, 7 women). During both protocols, participants were supine for 5 min during measurement of beat-to-beat blood pressure (photoplethysmography) and R-R interval (ECG). cBRS was evaluated using the sequence method. Root mean square of successive differences in R-R interval (RMSSD) was used as an index of HRV. Serum sodium (137.4 ± 0.7 vs. 139.9 ± 0.5 meq/l, P < 0.05), plasma osmolality (285 ± 1 vs. 289 ± 1 mosmol/kgH2O, P < 0.05), cBRS (18 ± 2 vs. 26 ± 3 ms/mmHg, P < 0.05), and RMSSD (62 ± 6 vs. 79 ± 10 ms, P < 0.05) were increased following high-sodium diet intake compared with low-sodium diet intake. HSI increased serum sodium (138.1 ± 0.4 vs. 141.1 ± 0.5 meq/l, P < 0.05) and plasma osmolality (286 ± 1 vs. 290 ± 1 mosmol/kgH2O, P < 0.05) but did not change cBRS (26 ± 5 vs. 25 ± 3 ms/mmHg, P = 0.73) and RMSSD (63 ± 9 vs. 63 ± 8 ms, P = 0.99). These data suggest that alterations in dietary sodium intake alter cBRS and HRV but that acute intravenous sodium loading does not alter these indexes of autonomic cardiovascular regulation.
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Can natural ways to stimulate the vagus nerve improve seizure control?
Yuen, AW, Sander, JW
Epilepsy & behavior : E&B. 2017;:105-110
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Abstract
The vagus nerve (VN) is the longest cranial nerve, innervating the neck, thorax and abdomen, with afferent fibers transmitting a range of interoceptive stimuli and efferent fibres to somatic structures and autonomic preganglions. Over the last few decades, electrical stimulation of the VN using implanted devices (VNS) has been developed leading to its approval for the treatment of epilepsy and depression. More recently, non-invasive devices to stimulation the VN have been developed. The VN has many functions and the activity that is most amenable to assessment is its effect in controlling the cardiac rhythm. This can be easily assessed by measuring heart rate variability (HRV). Decreased HRV is a result of poorer vagal parasympathetic tone and is associated with a wide range of ill health conditions including a higher risk of early mortality. People with epilepsy, particularly those with poorly controlled seizures, have been shown to have impaired parasympathetic tone. So, might natural ways to stimulate the VN, shown to improve parasympathetic tone as indicated by increased HRV, improve seizure control? There are numerous natural ways that have been shown to stimulate the VN, improving HRV and hence parasympathetic tone. These natural ways fall mainly into 3 categories - stress reduction, exercise, and nutrition. Though the natural ways to stimulate the VN have been shown to increase HRV, they have not been shown to reduce seizures. The exception is listening to Mozart's music, which has been shown to increase parasympathetic tone and decrease seizures. Clearly much more work is required to examine the effect of the various ways to increase HRV on seizure occurrence.
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Near-infrared spectroscopy (NIRS) and vagus somatosensory evoked potentials (VSEP) in the early diagnosis of Alzheimer's disease: rationale, design, methods, and first baseline data of the Vogel study.
Polak, T, Herrmann, MJ, Müller, LD, Zeller, JBM, Katzorke, A, Fischer, M, Spielmann, F, Weinmann, E, Hommers, L, Lauer, M, et al
Journal of neural transmission (Vienna, Austria : 1996). 2017;(11):1473-1488
Abstract
Functional near-infrared spectroscopy (fNIRS) and vagus somatosensory evoked potentials (VSEP) show deviant patterns in subjects with Alzheimer's disease (AD) compared to healthy controls. We now aimed at testing the predictive value of these methods in the early diagnosis of AD. The Vogel study is a prospective, observational, long-term follow-up study with three time points of investigation within 6 years. Residents of the city of Würzburg born between 1936 and 1941 were recruited. Every participant underwent physical, psychiatric, and laboratory examinations, and performed an intense neuropsychological testing as well as VSEP and NIRS according to the published procedures. 604 subjects were included. Mean age of the participants was 73.9 ± 1.55 years. The most frequent pathological physical and laboratory examination results were observed for blood pressure (62%), body weight (54%), HbA1c (16%), cholesterol (42%), and homocysteine (69%). Comprehensive analysis of cognitive testing showed mild cognitive impairment (MCI) in 12.3% of the patients. Concurrent major depression was found in 6.6% of the patients. We observed a high rate of MCI and somatic comorbidity in our cohort. The high rate of vascular risk factors and depressive symptoms, all of which are known risk factors of AD, is consistent with the notion that there are multiple options to prevent or postpone the onset of AD in a geriatric population like the one of the Vogel studies.