Sympathetic Nervous System Activity Research Articles

To what degree patient-reported symptoms of central sensitization, kinesiophobia, disability, sleep, and life quality associated with 24-h heart rate variability and actigraphy measurements?

Chronic musculoskeletal pain is associated with decreased parasympathetic and increased sympathetic activity in the autonomic nervous system. The objective of this study was to determine the associations between objective measures of heart rate variability (a measure of autonomic nervous system function), actigraphy (a measure of activity and sleep quality), respiration rates, and subjective patient-reported outcome measures (PROMs) of central sensitization, kinesiophobia, disability, the effect of pain on sleep, and life quality. Thirty-eight study subjects were divided into two subgroups, including low symptoms of central sensitization (n = 18) and high symptoms of central sensitization (n = 20), based on patient-reported scores on the Central Sensitization Inventory (CSI). Heart rate variability (HRV) and actigraphy measurements were carried out simultaneously in 24 h measurement during wakefulness and sleep. A decrease in HRV during the first 2 h of sleep was stronger in the low CSI subgroup compared to the high CSI subgroup. Otherwise, all other HRV and actigraphy parameters and subjective measures of central sensitization, disability, kinesiophobia, the effect of pain on sleep, and quality of life showed only little associations. The high CSI subgroup reported significantly more severe symptoms of disability, kinesiophobia, sleep, and quality of life compared to the low CSI subgroup. However, there were only small and nonsignificant trend in increased sympathetic nervous system activity and poorer sleep quality on the high central sensitization subgroup. Moreover, very little differences in respiratory rates were found between the groups.

Genetic and environmental influences on alpha amylase stress reactivity and shared genetic covariation with cortisol

Salivary alpha amylase (sAA) is a common measure of stress reactivity, primarily reflecting sympathetic nervous system activity. Salivary cortisol is also a reliable, frequently used biomarker of stress and reflects the hypothalamic-pituitary-adrenal (HPA) axis response. This study examined heritability across varying metrics of sAA in response to a social evaluative stressor, the Trier Social Stress Test (TSST). The goal of this study was to estimate genetic and environmental influences on measurements of sAA stress reactivity. Moreover, we evaluated the shared genetic covariation between sAA and cortisol. Participants included twins aged 15–20 years (54% female). We measured alpha amylase and cortisol reactivity to the TSST via serial salivary cortisol samples collected pre- and post-TSST. Modest to moderate heritability estimates (11–64%) were observed across measures purported to capture alpha amylase stress reactivity (peak, area under the curve, baseline-to-peak change). Findings also indicate that sAA baseline and peak are primarily influenced by a shared genetic factor. There was no evidence of shared genetic influences between sAA and cortisol. These findings suggest the genetic control of the HPA and Sympathetic Adreno-Medullar axis are genetically independent of one another despite both playing a role in response to stressors.

Stress system dysfunction and changes in brain volume and functional connectivity in older adults with subclinical depressive symptoms

AbstractBackgroundSubclinical depressive symptoms are associated with increased risk of Alzheimer’s disease (AD). This link could be related to stress system dysfunction, known to occur in both depression and AD, and to depend notably on the hippocampus which is particularly sensitive to AD. We aimed at investigating the links between levels of blood stress markers and changes in brain regions involved in the stress response in older adults with subclinical depressive symptoms.MethodCognitively unimpaired older adults with (DepS; n = 73) or without (NoDepS; n = 58) subclinical depressive symptoms (defined using the 15‐item version of the Geriatric Depression Scale), from the baseline data of the Age‐Well trial (NCT02977819) were included. For each participant, levels of cortisol, epinephrine and norepinephrine were obtained from blood sampling. Moreover, the functional connectivity (FC) between, and the gray matter (GM) volume of, the hypothalamus, hippocampus and hippocampal subfields were extracted from resting‐state functional, and structural T1‐weighted, MRI. Levels of blood stress markers and neuroimaging measures were compared between groups. Regression analyses were then conducted between levels of blood markers and brain measures. Analyses were corrected for age, sex, education and anxiety symptoms with statistical significance set to p<0.05.ResultHigher blood epinephrine level (p<0.024), and FC between the hypothalamus and the CA1 hippocampal subfield (p<0.040), was found in DepS compared to NoDepS (Fig.1). This higher epinephrine level was associated with greater FC between the hypothalamus and the CA1 (p<0.007) and Subiculum (p<0.013) subfields (Fig.2). Lower GM volume in the CA1 (p<0.008) and DG/CA2‐3‐4 (p<0.013) subfields was also found in the DepS group (Fig.3), but was not associated with epinephrine level. No significant between‐group difference in blood cortisol and norepinephrine levels was observed.ConclusionSubclinical depressive symptoms in aging are associated with higher blood epinephrine level related to greater FC between the hypothalamus and hippocampal subfields (CA1 and Subiculum) – suggesting an increased sympathetic nervous system activity. They are also associated with GM atrophy in specific hippocampal subfields, including the CA1 that is sensitive to AD. These two distinct mechanisms at this preclinical stage of depression may at least partly explain that depression is a risk factor for AD.

Renal sympathetic denervation ameliorates the activated inflammatory response through JAK-STAT pathway in a chronic obstructive sleep apnea animal model

ObjectivesObstructive sleep apnea (OSA) is known to increase the risk of cardiovascular disease and inflammation plays a significant role in this process. Renal denervation (RDN) is a novel approach aimed at reducing sympathetic nervous system activity. The role of RDN in the inflammatory response to chronic OSA (COSA) is currently unclear. The main objective was to study inflammatory mechanisms in the rabbit heart with COSA and the effects of RDN. MethodsEighteen rabbits were randomized into three groups: sham control, COSA, and COSA-RDN. COSA and COSA-RDN groups received liquid silicone injections, while the sham control group received normal saline. We performed combined surgical and chemical RDN through bilateral retroperitoneal flank incisions in the COSA-RDN group after silicone injections. The inflammatory mechanisms were assessed through immunoblotting, real-time PCR, and ELISA after the experiment. ResultsH&E staining showed immune cell infiltration in COSA, which decreased after RDN treatment. The level of α7nAChR was significantly reduced in COSA compared to the sham control but was restored to a similar level in the COSA-RDN group. Furthermore, the expressions of p-JAK2 and p-STAT3 were significantly reduced in COSA but showed an up-regulation following RDN treatment. Similarly, levels of the inflammatory markers IL-6, IL-1β and TNF-α were markedly increased in COSA but decreased after RDN therapy. We observed NF-κB activation in the COSA rabbit model, which decreased after RDN treatment, as evidenced by decreased NF-κB expression. ConclusionsOur study suggests that RDN treatment may prevent COSA-associated heart inflammation via the JAK2-STAT3 signaling pathway.

Impedance cardiogram based exploration of cardiac mechanisms in post-traumatic stress disorder during trauma recall.

Post-traumatic stress disorder (PTSD) is an independent risk factor for developing heart failure; however, the underlying cardiac mechanisms are still elusive. This study aims to evaluate the real-time effects of experimentally induced PTSD symptom activation on various cardiac contractility and autonomic measures. We recorded synchronized electrocardiogram and impedance cardiogram from 137 male veterans (17 PTSD, 120 non-PTSD; 48 twin pairs, 41 unpaired singles) during a laboratory-based traumatic reminder stressor. To identify the parameters describing the cardiac mechanisms by which trauma reminders can create stress on the heart, we utilized a feature selection mechanism along with a random forest classifier distinguishing PTSD and non-PTSD. We extracted 99 parameters, including 76 biosignal-based and 23 sociodemographic, medical history, and psychiatric diagnosis features. A subject/twin-wise stratified nested cross-validation procedure was used for parameter tuning and model assessment to identify the important parameters. The identified parameters included biomarkers such as pre-ejection period, acceleration index, velocity index, Heather index, and several physiology-agnostic features. These identified parameters during trauma recall suggested a combination of increased sympathetic nervous system (SNS) activity and deteriorated cardiac contractility that may increase the heart failure risk for PTSD. This indicates that the PTSD symptom activation associates with real-time reductions in several cardiac contractility measures despite SNS activation. This finding may be useful in future cardiac prevention efforts.

Sympathetic nervous system responses during complex walking tasks and community ambulation post-stroke

Stroke survivors frequently report increased perceived challenge of walking (PCW) in complex environments, restricting their daily ambulation. PCW is conventionally measured through subjective questionnaires or, more recently, through objective quantification of sympathetic nervous system activity during walking tasks. However, how these measurements of PCW reflect daily walking activity post-stroke is unknown. We aimed to compare the subjective and objective assessments of PCW in predicting home and community ambulation. In 29 participants post-stroke, we measured PCW subjectively with the Activities-specific Balance Confidence (ABC) Scale and objectively through electrodermal activity, quantified by change in skin conductance levels (SCL) and skin conductance responses (SCR) between outdoor-complex and indoor-steady-state walking. High-PCW participants were categorized into high-change SCL (ΔSCL ≥ 1.7 μs), high-change SCR (ΔSCR ≥ 0.2 μs) and low ABC (ABC < 72%) groups, while low-PCW participants were categorized into low-change SCL (ΔSCL < 1.7 μs), low-change SCR (ΔSCR < 0.2 μs) and high-ABC (ABC ≥ 72%) groups. Number and location of daily steps were quantified with accelerometry and Global Positioning System devices. Compared to low-change SCL group, the high-change SCL group took fewer steps in home and community (p = 0.04). Neither ABC nor SCR groups differed in home or community steps/day. Objective measurement of PCW via electrodermal sensing more accurately represents home and community ambulation compared to the subjective questionnaire.

Thyroid gland dysfunction in heart rhythm disorders

Thyroid gland dysfunction is estimated to occur in approximately 5% of the population and affects people of different ages. Cardiovascular diseases can occur in diseases such as hyperthyroidism as well as hypothyroidism. Increased thyroid hormone levels precipitate sympathetic nervous system activation, potentially culminating in heightened heart rate (tachycardia) and disruptions in electrical conduction. This influence can induce QT interval shortening and provoke premature ventricular contractions (PVCs), amplifying the propensity for more severe arrhythmic manifestations. Insufficiency of thyroid hormones decelerates metabolic activity, potentially leading to bradycardia. Hypothyroidism elevates the risk of atrial fibrillation occurrence and additionally elongates QT intervals, enhancing the susceptibility to torsade de pointes. Untreated hormone disorders affect severe cardiac complications, which can occur in patients with previously diagnosed heart disease. Effective management of cardiac arrhythmias in patients with thyroid dysfunction necessitates interdisciplinary collaboration between endocrinologists and cardiologists.

Mechanisms and treatment of obesity-related hypertension-Part 1: Mechanisms.

The prevalence of obesity has tripled over the past five decades. Obesity, especially visceral obesity, is closely related to hypertension, increasing the risk of primary (essential) hypertension by 65%-75%. Hypertension is a major risk factor for cardiovascular disease, the leading cause of death worldwide, and its prevalence is rapidly increasing following the pandemic rise in obesity. Although the causal relationship between obesity and high blood pressure (BP) is well established, the detailed mechanisms for such association are still under research. For more than 30 years sympathetic nervous system (SNS) and kidney sodium reabsorption activation, secondary to insulin resistance and compensatory hyperinsulinemia, have been considered as primary mediators of elevated BP in obesity. However, experimental and clinical data show that severe insulin resistance and hyperinsulinemia can occur in the absence of elevated BP, challenging the causal relationship between insulin resistance and hyperinsulinemia as the key factor linking obesity to hypertension. The purpose of Part 1 of this review is to summarize the available data on recently emerging mechanisms believed to contribute to obesity-related hypertension through increased sodium reabsorption and volume expansion, such as: physical compression of the kidney by perirenal/intrarenal fat and overactivation of the systemic/renal SNS and the renin-angiotensin-aldosterone system. The role of hyperleptinemia, impaired chemoreceptor and baroreceptor reflexes, and increased perivascular fat is also discussed. Specifically targeting these mechanisms may pave the way for a new therapeutic intervention in the treatment of obesity-related hypertension in the context of 'precision medicine' principles, which will be discussed in Part 2.

Remote ischemic peri-conditioning suppressed the activation of cardiac sympathetic nervous system in patients with acute myocardial infarction: a randomized controlled trial

Abstract Background The activation of cardiac sympathetic nervous system is associated with poor prognosis in patients with acute myocardial infarction (AMI). Remote ischemic peri-conditioning (RIPC) is reported to improve clinical outcome in patients with AMI. However, there is not fully clarified whether RIPC could have an effect on cardiac sympathetic activity. Purpose The purpose of this study is to investigate the effect of RIPC on cardiac sympathetic activity in patients with AMI. Methods We randomly assigned 157 patients with suspected AMI undergoing emergent percutaneous coronary intervention to receive transient limb ischemia (by inflating a cuff at 200 mmHg for 4×5 minutes: RIPC group, n=77) or no procedure (control group, n=80) upon arrival to the cardiac catheterization laboratory. After excluding inappropriate patients such as those who were diagnosed with other than AMI, we analyzed 122 patients (62 patients in RIPC and 60 in control group). The primary endpoint was cardiac sympathetic activity assessed by the cardiac MIBG imaging washout rate (WR) at discharge and 1 year after discharge. WR and late heart-to-mediastinum ratio (HMR) in cardiac MIBG was calculated from the chest anterior view images obtained at 20 and 200 min after isotope injection. Results Patients in RIPC and control group had similar demographic and clinical characteristics at baseline. There was no significant difference in WR between two groups at discharge. Although WR was significantly decreased 1 year after the discharge in both groups, patients in RIPC group showed significantly lower WR than those in control group (22.0 [15.1-30.6]% and 26.5 [18.4-34.4]%, p=0.0269) 1 year after the discharge. Late HMR significantly decreased during 1-year follow-up in patients only in RIPC group (p=0.0133) and patients in RIPC group tended to show higher late HMR compared to those in control group (2.01 [1.79-2.25] and 1.92 [1.72-2.11], p=0.0581) 1 year after the discharge. Conclusion(s) Remote ischemic peri-conditioning could suppress the augmented cardiac sympathetic activity in patients with acute myocardial infarction during 1-year follow-up.

Comparison between biofeedback Acapella and biofeedback flutter devices in COPD: A new way to improve airway clearance

Introduction and Aim: In recent years, biofeedback systems have been integrated into a variety of devices. Biofeedback system is the process of gaining awareness of one's physiological functions by an apparatus which provides participants feedback of their performance. Respiratory training with a biofeedback system provides the correct breathing pattern, reduces respiratory rate and tension, enhances respiratory function, improves gaseous exchange, improves ventilation and perfusion mismatch. Therefore, it reduces sympathetic nervous system activity by clearing secretions. As clearing the mucous from the airways is the initial stage of respiratory rehabilitation, this study sought to implement a biofeedback system in an Acapella and flutter device and compared the effectiveness of both the positive expiratory pressure (PEP) devices (Acapella and Flutter) with biofeedback on lung functions in chronic obstructive pulmonary disease (COPD) patients.&#x0D; &#x0D; Materials and Methods: 30 patients were assigned randomly to the acapella group or the flutter group with 15 patients in each group. The Acapella biofeedback group used the Biofeedback Acapella device for 15-20 minutes per day for five days, while the Flutter biofeedback group used the Biofeedback Flutter device simultaneously.&#x0D; &#x0D; Results: The biofeedback acapella group and the biofeedback flutter group showed significantly higher increases in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and oxygen saturation (SpO2). There was no significant difference between the groups. In addition, there was a significant difference in sputum weight, within both the groups reducing significant amounts of sputum and improving symptoms.&#x0D; &#x0D; Conclusion: These results suggest that both Biofeedback Acapella device and the Biofeedback Flutter device help in improving lung function and oxygen saturation in COPD patients. Further scientific studies are needed to be performed to confirm the results and to determine the optimal durations and frequencies used in these devices. We also recommend further improvement and development of airway clearance devices.

Dapagliflozin downregulates G protein-coupled receptor Kinase-2 and upregulates regulator of g protein signaling-4 in adrenals to exert sympatholysis in heart failure

Abstract Dapagliflozin is a sodium-glucose co-transporter (SGLT)-2 inhibitor with beneficial cardiovascular effects independent of its anti-diabetic actions. Among these is sympatholysis, i.e., norepinephrine (NE) lowering which is beneficial in chronic human heart failure (HF). Adrenal G protein-coupled receptor kinase (GRK)-2 upregulation is a major driver of circulating catecholamine (CA) elevation and sympathetic nervous system (SNS) hyperactivity in HF due to dysregulation of adrenal sympatho-inhibitory α2-adrenergic receptors (ARs) [1]. On the other hand, we recently reported that signaling by neuronal free fatty acid receptor (FFAR)-3, which stimulates NE release from sympathetic neurons, is blocked by Regulator of G protein Signaling (RGS)-4 [2,3]. We hypothesized herein that dapagliflozin may lower SNS hyperactivity in the adrenal gland by improving α2AR, and antagonizing FFAR3 signaling in adrenal chromaffin cells. We used the rat pheochromocytoma PC12 cell line expressing human α2A-AR, as well as freshly isolated adrenal glands from rats treated with dapagliflozin in vivo. Dapagliflozin treatment for 7 consecutive days (20 mg/kg/d in drinking water) led to a significant reduction in blood circulating NE levels (217+67 pg/ml, n=6), compared to control, vehicle-treated rats (363+77 pg/ml, n=6, p&amp;lt;.05), suggesting reduced SNS activity. This was accompanied by reduced GRK2 and tyrosine hydroxylase (TH) mRNA and protein levels in dapagliflozin-treated rat adrenals vs. vehicle-treated animal-derived glands. In contrast, RGS4 mRNA levels were increased in dapagliflozin-treated adrenals. Adrenal α2AR density was higher in dapagliflozin- vs. vehicle-treated rats (51.3+7.3 vs. 26.1+8.1 fmol/mg of protein, respectively; n=12 glands from 6 animals per group, p&amp;lt;.05). These results (i.e., GRK2 &amp; TH downregulation with RGS4 upregulation) were completely recapitulated in PC12 cells in culture, treated with 5 microM dapagliflozin (or vehicle) for 24 hours. Importantly, α2AR-dependent G protein-mediated signaling towards inhibition of CA secretion was markedly enhanced, whereas FFAR3-dependent phospholipase C/calcium signaling was reduced, at 24 hrs post-dapagliflozin treatment of PC12 cells. GRK2 overexpression partially reversed dapagliflozin`s effect on cholinergic-induced CA secretion. In conclusion, dapagliflozin exerts a sympatholytic action in the adrenal medulla via a) downregulation of TH, which reduces CA biosynthesis, and GRK2, which reduces α2AR desensitization; and b) upregulation of RGS4 to block FFAR3-stimulated CA secretion (Figure).Figure

Abstract 15000: Renal Denervation Improves Cardiac Function and Mitigates Pathophysiological Changes in a Novel Murine Model of Heart Failure With Preserved Ejection Fraction

Introduction: Heart Failure with Preserved Ejection Fraction (HFpEF) is a multifaceted disease, intricately linked with sympathetic nervous system activation. Despite advancements, therapeutic options for HFpEF remain constrained, largely due to a dearth of fitting preclinical models. Renal denervation (RDN), an emerging intervention, holds potential in attenuating sympathetic activity and ameliorating HFpEF high-risk factors such as hypertension and insulin resistance. Aims: our study is designed to establish a multifactorial HFpEF mouse model and assess the therapeutic implications of RDN. Methods: Aged 12-month-old male C57BL/6N mice were exposed to a high-fat diet (60% calories from lard) and L-NAME (0.5 g/L in drinking water) over a 5-week period to generate a multi-hit HFpEF model. The efficacy of the model was assessed through a range of methods, encompassing echocardiography, histology, exercise exhaustion tests, serum NT-proBNP measurements, and intraperitoneal glucose tolerance tests. Upon successful model establishment, mice were randomized to receive either bilateral renal denervation or a sham operation. The subsequent impact of RDN on the aforementioned parameters was then evaluated. Results: In C57BL/6N mice, a cardiometabolic HFpEF phenotype was effectively induced through a multi-hit approach encompassing a high-fat diet, L-NAME administration, and aging. This potent combination triggered obesity and glucose intolerance, culminating in the emergence of characteristic HFpEF features such as cardiac hypertrophy, fibrosis, preserved fractional shortening with impaired deformation, atrial enlargement, lung congestion, hypertension and decreased exercise endurance. Intervention with RDN mitigated this cardiometabolic dysregulation and enhanced cardiac function, as demonstrated by reductions in cardiac hypertrophy, myocardial fibrosis, atrial weight, NT-proBNP levels, lung congestion, and improved exercise endurance. Conclusions: Our study suggests that RDN effectively mitigates cardiac function and structure in a multi-hit HFpEF mouse model, indicating its potential as a promising therapeutic strategy for HFpEF.

Abstract 14584: Differences in Pupillary Reflex Between Patients With Acute Heart Failure and Healthy Subjects. An Easy New Marker of Treatment Control in Heart Failure

Introduction: In heart failure (HF), the sympathetic nervous system (SNS) is overactivated to try to maintain an adequate cardiac output. The pupillary reflex depends on the SNS and may be a new prognostic marker. Hypothesis: Pupillary reflex of patients with decompensated HF differs compared to controls, due to the hyperactivation of the SNS in acute HF. HF treatment may change pupillary reflex and may serve as a new marker of therapy. Aims: The aim was to compare the difference pupillary reflex between patients with acute HF and controls that may offer a new and easy prognostic factor in such patients. Methods: 107 pupillometry values of patients with decompensated HF were performed with NeuroOptics pupillometer prospectively and consecutively on admission and discharge, and compared with 42 pupillometry of controls. Results: HF patients have higher BMPD, higher MinPD and higher LC than controls.Patients with HF had higher BMPD and higher MinPD at admission vs. discharge (P&lt;0.05). No significant differences were seen between HF patients at discharge and controls. It may be that pupillary reflex values reflect better disease control at discharge. Conclusions: Patients with decompensated HF have a higher BMPD and higher MinPD. Also, HF patients presented an improvement in pupillometric values at discharge and showed no differences compared to controls.This supports the hypothesis that patients with decompensated HF present a hyperactivation of the SNS that promotes mydriasis versus miosis. SNS activity is difficult to evaluate; the pupillary reflex can be a simple and useful tool to determine its status, establish prognostic, and could help to control therapeutic management.

Psychologically aggressive parenting and later aggression: Salivary alpha-amylase reactivity and sex as moderators

Psychologically aggressive parenting (PAP) exposure negatively affects children's development of aggression. Nevertheless, not all children exposed to PAP display aggressive behaviors. Sympathetic nervous system (SNS) activity may influence the impact of early adversity on aggression. This study examines whether SNS reactivity and sex moderate the link between psychologically aggressive parenting (PAP) during childhood and later aggression. Emerging adults (N = 182, mean age = 19.03 years, 53 % female) retrospectively reported on their childhood PAP and current aggression. Salivary alpha-amylase (sAA) collected from a social stress task indexed SNS reactivity to stress. Childhood PAP was associated with emerging adulthood anger, hostility, physical, and verbal aggression. Moreover, males were more likely to exhibit anger, verbal, and physical aggression and had higher levels of sAA reactivity than females. A significant three-way interaction between childhood PAP, sAA reactivity, and sex accounted for participants' current verbal aggression. The link between childhood PAP and later verbal aggression was stronger for males at higher levels of sAA reactivity. Females with higher levels of sAA reactivity displayed lower levels of verbal aggression regardless of PAP exposure. Males and females with lower levels of sAA reactivity were at elevated risk for verbal aggression regardless of PAP exposure. Moreover, we found a significant two-way interaction between PAP and sex on anger, such that higher levels of PAP exposure were associated with more anger among males, but not females. These findings highlight the importance of examining interactions between biological and environmental factors and sex in accounting for later aggression.

Parameters of the P300 auditory evoked potential and autonomic heart rate regulation in adolescents residing in different climatic and geographical conditions of Russia

BACKGROUND: The physiological functions and body development take place as the body adapts to the environment. For schoolchildren aged 16-17, their primary focus is on studying, which involves processing and retaining a significant volume of diverse information. The P300 auditory evoked potential reflects the neurophysiological aspects of cognitive functions such as attention and memory. This assessment is particularly relevant when considering the autonomic heart rate regulation in young individuals residing in the northern and southern regions of Russia.&#x0D; AIM: The objective of this study was to assess the auditory evoked potential components, namely P300 and N2, along with heart rate variability parameters in a group of healthy young Russian adolescents living in different climatic and geographical conditions.&#x0D; MATERIAL AND METHODS: The study sample consisted of 156 individuals aged 1617 years permanently residing in Arkhangelsk, Nadym and Simferopol. The assessment of the autonomic nervous system was carried out according to the parameters of heart rate variability on the agro-industrial complex Varikard. Registration of P300 and N2 components was carried out on the Neuron-Spectrum-4/VPM electroencephalograph (Neurosoft, Russia), using the oddball paradigm.&#x0D; RESULTS: The predominance of sympathetic nervous system activity in the regulation of heart rate and the lengthening of the N2 latency was revealed in adolescents in Nadym. In residents of Arkhangelsk and Simferopol, there were no differences in the parameters of heart rate variability and components of the auditory evoked potential of P300. Interhemispheric asymmetry of N2 latency was observed in young people of Arkhangelsk, where the time was shorter in the central (C4, p=0.04) and right anterior temporal (F8, p=0.01) sections.&#x0D; CONCLUSIONS: The imbalance in the autonomic nervous system towards the predominance of sympathetic influences in the heart rate regulation is reflected in slower recognition and differentiation of the sound signal.

PSVII-14 Reduction in Heart Rate Variability Parameters in Horses Treated with a Mixture of Lavender and Eucalyptus Essential Oil

Abstract Routine medical examinations can produce stress which can negatively impact the health and well-being of horses. Heart rate variability (HRV) is a non-invasive and inexpensive method to measure the balance between sympathetic and parasympathetic nervous system activity, which can help identify stress in horses. This study examined the effect of a combination of lavender and eucalyptus essential oil on stress responses in horses undergoing a routine medical exam. After a five-minute stall rest (baseline reading) data were collected in three, five-minute intervals (walk to and enter stock, medical exam, and recovery in stall). This study utilized a switch-back design where each horse (n = 10) received both treatments on different dates. The treatment groups received lavender (20%) and eucalyptus essential oil (5%) dissolved in petroleum jelly and virgin sunflower oil applied to inner nostrils. The control treatment consisted of only petroleum jelly and virgin sunflower oil applied to inner nostrils. The root mean square of the successive differences of heartbeats (RMSSD) was significantly reduced (P &amp;lt; 0.05) when horses were treated with essential oils while walking to stocks (51.7 ± 3.7), during the medical exam (50.5 ± 4.9), and during the recovery period (64.1.9 ± 5.7) compared with control treatment, to stocks (36.1 ± 4.4), the medical exam (39.0 .± 4.5), and during the recovery period (49.7 ± 5.5). The measured SD1 (parasympathetic) was significantly greater (P &amp;lt; 0.008) at walk to stocks in horses treated with essential oils (37.2 ± 1.9) compared with control treated (30.3 ± 3.1). The measured SD2 (sympathetic) was significantly less (P &amp;lt; 0.008) at walk to stocks in horses treated with essential oils (62.8 ± 1.9) compared with control treated (69.7 ± 6.8). The ratio of SD1/SD2 was significantly less (P &amp;lt; 0.008) at walk to stocks in horses treated with essential oils (1.7 ± 0.17) compared with control treated (2.4 ± 0.26). The high frequency percent (HF%) was also greater (P &amp;lt; 0.04) at walk to stocks in horses treated with essential oils (39.6 ± 4.9) compared with control treated (26.0 ± 4.1). The standard deviation of RR Interval (SDNN) values were increased (P &amp;lt; 0.03) in horses treated with essential oils during walking to stalks (50.8 ± 1.9), the medical exam (56.7 ± 5.0), and the recovery period (72.4 ± 12.9) compared with the control treatment, to stalks (44.5 ± 5.2), medical exam (44.0 ± 4.5), and during the recovery period (54.6 ± 6.2). The results of this study indicate that lavender and eucalyptus oil could be an effective means of reducing short-term stress in horses. The findings of this study can help develop more effective and humane management strategies for horses.

Continuous Physiological Monitoring of the Combined Exposure to Hypoxia and High Cognitive Load in Military Personnel.

Military aviators endure high cognitive loads and hypoxic environments during flight operations, impacting the autonomic nervous system (ANS). The synergistic effects of these exposures on the ANS, however, are less clear. This study investigated the simultaneous effects of mild hypoxia and high cognitive load on the ANS in military personnel. This study employed a two-factor experimental design. Twenty-four healthy participants aged between 19 and 45 years were exposed to mild hypoxia (14.0% O2), normoxia (21.0% O2), and hyperoxia (33.0% O2). During each epoch (n = 5), participants continuously performed one 15 min and one 10 min series of simulated, in-flight tasks separated by 1 min of rest. Exposure sequences (hypoxia-normoxia and normoxia-hyperoxia) were separated by a 60 min break. Heart rate (HR), heart rate variability (HRV), and O2 saturation (SpO2) were continuously measured via an armband monitor (Warfighter MonitorTM, Tiger Tech Solutions, Inc., Miami, FL, USA). Paired and independent t-tests were used to evaluate differences in HR, HRV, and SpO2 within and between exposure sequences. Survival analyses were performed to assess the timing and magnitude of the ANS responses. Sympathetic nervous system (SNS) activity during hypoxia was highest in epoch 1 (HR: +6.9 bpm, p = 0.002; rMSSD: -9.7 ms, p = 0.003; SDNN: -11.3 ms, p = 0.003; SpO2: -8.4%, p < 0.0000) and appeared to slightly decline with non-significant increases in HRV. During normoxia, SNS activity was heightened, albeit non-significantly, in epoch 1, with higher HR (68.5 bpm vs. 73.0 bpm, p = 0.06), lower HRV (rMSSD: 45.1 ms vs. 38.7 ms, p = 0.09 and SDNN: 52.5 ms vs. 45.1 ms, p = 0.08), and lower SpO2 (-0.7% p = 0.05). In epochs 2-4, HR, HRV, and SpO2 trended towards baseline values. Significant between-group differences in HR, HRV, and O2 saturation were observed. Hypoxia elicited significantly greater HRs (+5.0, p = 0.03), lower rMSSD (-7.1, p = 0.03), lower SDNN (-8.2, p = 0.03), and lower SpO2 (-1.4%, p = 0.002) compared to normoxia. Hyperoxia appeared to augment the parasympathetic reactivation reflected by significantly lower HR, in addition to higher HRV and O2 relative to normoxia. Hypoxia induced a greater ANS response in military personnel during the simultaneous exposure to high cognitive load. The significant and differential ANS responses to varying O2 levels and high cognitive load observed highlight the importance of continuously monitoring multiple physiological parameters during flight operations.

Sex differences in Black Veterans with PTSD: women versus men have higher sympathetic activity, inflammation, and blunted cardiovagal baroreflex sensitivity.

Post-traumatic stress disorder (PTSD) is associated with greater risk of incident hypertension and cardiovascular disease (CVD). Inflammation and autonomic derangements are suggested as contributing mechanisms. Women and Black adults have higher CVD risk associated with stress; however, whether there is a sex difference in autonomic and inflammatory mechanisms among Black individuals with PTSD is not known. We hypothesized that Black women with PTSD have higher inflammation, sympathetic nervous system (SNS) activity and impaired baroreflex sensitivity (BRS). In 42 Black Veterans with PTSD (Women, N = 18 and Men, N = 24), we measured inflammatory biomarkers, continuous blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) at rest and during arterial BRS testing via the modified Oxford technique. Groups were matched for age and body mass index (BMI). Resting BP was similar between groups, but HR was higher (76 ± 12 vs. 68 ± 9 beats/min, p = 0.021) in women compared to men. Although women had lower PTSD symptoms severity (57 ± 17 vs. 68 ± 12 a.u.), resting MSNA (27 ± 13 vs. 16 ± 5 bursts/min, p = 0.003) was higher in women compared to men, respectively. Likewise, cardiovagal BRS was blunted (p = 0.002) in women (7.6 ± 4.3ms/mmHg) compared to men (15.5 ± 8.4ms/mmHg) while sympathetic BRS was not different between groups (p = 0.381). Black women also had higher (p = 0.020) plasma levels of interleukin-2 (IL-2). Black women with PTSD have higher resting HR and MSNA, greater impairment of cardiovagal BRS and possibly higher inflammation. These findings suggest a higher burden of autonomic and inflammatory derangements in Black women compared to Black men with PTSD.

Effects of prenatal opioid exposure on infant sympathetic and parasympathetic nervous system activity.

Prenatal opioid exposure has been associated with developmental problems, including autonomic nervous system dysregulation. However, little is known about the effects of prenatal opioid exposure on the autonomic nervous system beyond the first days of life, particularly across both the parasympathetic and sympathetic branches, and when accounting for exposure to other substances. The present study examined the effects of prenatal exposure to opioid agonist therapy (OAT, e.g., methadone) and other opioids on infant autonomic nervous system activity at rest and in response to a social stressor (the Still-Face Paradigm) at six months among 86 infants varying in prenatal opioid and other substance exposure. Results indicated that OAT and other opioids have unique effects on the developing autonomic nervous system that may further depend on subtype (i.e., methadone versus buprenorphine) and timing in gestation. Results are discussed in the context of theoretical models of the developing stress response system.

Study Protocol for the Pleiotropic Effects of Sodium-Glucose Cotransporter2 Inhibitor on Organ-Specific Sympathetic Nerve Activity and Insulin Sensitivity in Participants with Type2 Diabetes.

Hyperinsulinemia and hyperglycemia are associated with exaggerated systemic sympathetic nerve activity (SNA) in patients with type2 diabetes. Sodium-glucose cotransporter2 (SGLT2) inhibitors lower insulin levels, whereas sulfonylureas increase insulin levels. We will test whether these two classes of antidiabetic agents have different effects on SNA. The present study is an ongoing, 24-week, one-center (only Kanazawa University Hospital), open-label, randomized, parallel trial (jRCTs 041200035). Participants with type2 diabetes with multiple atherosclerosis risk factors are randomly assigned in a 1:1 manner to receive 2.5mg luseogliflozin or 0.5mg glimepiride once daily. The sample size was calculated to be 14 in each group, with a significance level of 0.05 and a power of 0.80. The design required 40 evaluable study participants. Our primary endpoint will be the change in muscle SNA (MSNA). The secondary endpoints included organ-specific insulin sensitivity measured by a hyperinsulinemic-euglycemic clamp study using an artificial pancreas combined with a stable isotope-labeled glucose infusion, bioelectrical impedance analysis, and organ-specific (cardiac, renal, and hepatic) 123I-meta-iodobenzylguanidine (MIBG) innervation imaging. Study recruitment started in April 2020 and will end in June 2024, with 40 participants randomized into the two groups. The treatment follow-up of the participants is currently ongoing and is due to finish by March 2025. The study protocol has been approved by the Certified Review Board, Kanazawa University, Ishikawa, Japan, in accordance with the guidelines stipulated in the Declaration of Helsinki (CRB4180005, 2019-001). This trial is registered with the Japan Registry of Clinical Trials, jRCTs 041200035.