Branches Of Autonomic Nervous System Research Articles

Effect of Exercise on Heart Rate - Curiosity Turned into an Experiment

The heart pumps and circulates the blood throughout the system, contracting and relaxing in a rhythm with each beat. The autonomic nervous system (ANS) controls involuntary body function (heart rate, BP, breathing and more), the sympathetic nervous system (SNS), a branch of ANS, is activated in response to exercise and stress. SNS activation releases hormones like epinephrine and norepinephrine, which cause an increase in heart rate involving specific receptors on heart cells. It is very well known how the nervous system controls the heart function, this review article summarizes the findings on sympathetic regulation of heart rate. Of note, some pilot experiments were conducted in random groups of high school students to elucidate the effect of exercise on heart rate. A statistically significant increase in heart rate was observed after exercise.

Cardiac Autonomic Balance Is Altered during the Acute Stress Response in Adolescent Major Depression-Effect of Sex.

Autonomic nervous system (ANS) abnormalities are associated with major depressive disorder (MDD) already at adolescent age. The majority of studies so far evaluated parasympathetic and sympathetic branches of ANS individually, although composite indices including cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR) seem to measure ANS functioning more comprehensively and thus could provide better psychopathologies' predictors. We aimed to study CAB and CAR derived from high-frequency bands of heart rate variability and left ventricular ejection time during complex stress response (rest-Go/NoGo task-recovery) in MDD adolescents with respect to sex. We examined 85 MDD adolescents (52 girls, age: 15.7 ± 0.14 yrs.) and 80 age- and sex-matched controls. The MDD group showed significantly reduced CAB compared to controls at rest, in response to the Go/NoGo task, and in the recovery phase. Moreover, while depressed boys showed significantly lower CAB at rest and in response to the Go/NoGo task compared to control boys, depressed girls showed no significant differences in evaluated parameters compared to control girls. This study for the first time evaluated CAB and CAR indices in drug-naïve first-episode diagnosed MDD adolescents during complex stress responses, indicating an altered cardiac autonomic pattern (i.e., reciprocal sympathetic dominance associated with parasympathetic underactivity), which was predominant for depressed boys.

Impact of Cancer and 12 Weeks of Chemotherapy on the Balance of the Autonomic Nervous System in Cancer Patients

Cancer and its treatment itself (especially chemotherapy) is associated with number of negative effects on the human body. These include mainly cardiac toxicity, peripheral neuropathy, bone loss, depression, anxiety, nausea, pain, cognitive changes, fatigue, fitness reduction and more. Fatigue is one of the most common negative effects, often persists long after treatment and is described as insurmountable and is associated with lower parasympathetic activity. The autonomic nervous system (ANS) is the main homeostatic regulatory system of the body, it regulates involuntary physiological processes. We believe that this part of the peripheral nervous system can be negatively affected by cancer and chemotherapy, which can have a negative impact on all the processes that control this system. Most drugs used in oncology lead to chemotherapy-induced peripheral neuropathy and are expected to have an influence on the autonomic nervous system. Activity and balance of the autonomic nervous system depend on a range of dynamically changing and quantitatively different conditions such as age, stress, physical activity, sleep, illness, fatigue and more. Methods: To evaluate ANS activity, spectral analysis of heart rate variability (HRV) was assessed. During treatment, 19 oncological patients with prescribed adjuvant chemotherapy measured HRV 3 times a week using a chest strap with a HRV monitor mySASY and mySASY software. Parasympathetic activity (PA), sympathetic activity (S), total score (TS) and total power (TP) were selected as indicators of ANS activity. The patients were women aged 50.38 ± 10,29 with BMI 25,72 ± 4,16. The mean values for the first 14 days of treatment and then for 14 days after 12 weeks of treatment were compared. Data normality was verified by Kolmogorov-Smirnov test (K-S) and static significance was calculated by t-test. All statistical tests were performed at a significance level of 5%. Results: There was a significant decrease in values for three parameters. The PA decreased from 3,80 ± 1,56 to 3,14 ± 1,67 (p = .03), TP decreased from 3,65 ± 1,87 to 2,82 ± 2,08 (p = .04), TS decreased from 3,40 ± 1,67 to 2,67 ± 1,73 (p = .01). Sympathetic activity was somewhat but not significantly higher, increased from 6,74 ± 1,22 to 6,80 ± 1,44 (p = .83). Conclusion: During the 12 weeks of treatment with adjuvant chemotherapy, there was a significant reduction in parasympathetic activity, total score, and total power. A decrease in PA is usually associated with lower regenerative abilities of the organism, a decrease in TP is associated with a decrease in the activity of the entire ANS. TS evaluates the total power and balance of both ANS branches. The higher the values, the more the body is regenerated and ready for further stress and response to stress.

AN EXPLORATORY STUDY OF PHYSIOLOGICAL AND BIOCHEMICAL PARAMETERS TO IDENTIFY SIMPLE, ROBUST AND RELEVANT BIOMARKERS FOR THERAPEUTIC INTERVENTIONS FOR PTSD: STUDY RATIONALE, KEY ELEMENTS OF DESIGN AND A CONTEXT OF WAR IN UKRAINE

Introduction. The incidence of post-traumatic stress disorder (PTSD) is increasing due to war in Ukraine is of growing importance as this disorder is a serious risk factor for alcohol/drug abuse, depression, suicide and functional dysregulation of internal organs, in particular cardiovascular, endocrine, immune systems. PTSD can also lead to social inadaptation in family and at work. This makes PTSD a very important social problem in Ukraine that causes significant economic damage, since most of the PTSD patients are young and in working age.
 Objectives. The purpose of this paper is to describe the rationale, key elements of design, methodology and future prospects of the ongoing project “Exploratory study of health related physiological and biochemical parameters to identify simple, robust and relevant biomarkers for therapeutic interventions for PTSD patients”.
 Methods. Short time ECG records (5 minutes in supine position and 6 minutes in orthostatic test) recorded by “CARDIOLAB” (Kharkiv, Ukraine) digital ECG device with software to analyze HRV was used to calculate time-domain and frequency-domain parameters of HRV.
 Results. The pattern of HRV changes indicates suppression of parasympathetic activity, low overall spectral power and dominance of sympathetic branch of autonomic nervous system in participants with PTSD.
 Conclusions. PTSD has no effective treatment so far and the best clinical practices rarely reach efficacy of 50%. The realization of the exploratory clinical study described in this paper will provide insights in the mechanisms underlying systemic consequences of PTSD and will build the evidence enabling clinical trial(s) for studying treatment intervention for patients with PTSD.

Heart rate variability as a marker of autonomic nervous system activity in young people with eosinophilic and non-eosinophilic asthma

Objective An imbalance in autonomic nervous system (ANS) activity may play a role in asthma, but it is unclear whether this is associated with specific pathophysiology. This study assessed ANS activity by measuring heart rate variability (HRV) in eosinophilic (EA) and non-eosinophilic asthma (NEA) and people without asthma. Methods HRV, combined hypertonic saline challenge/sputum induction, exhaled nitric oxide (FeNO), skin prick tests to measure atopy, and spirometry tests were conducted in teenagers and young adults (14–21 years) with (n = 96) and without (n = 72) generally well-controlled asthma. HRV parameters associated with sympathetic and parasympathetic ANS branches were analyzed. EA and NEA were defined using a 2.5% sputum eosinophil cut-point. Airway hyperreactivity (AHR) was defined as ≥15% reduction in FEV1 following saline challenge. Results HRV parameters did not differ between asthmatics and non-asthmatics or EA and NEA. They were also not associated with markers of inflammation, lung function or atopy. However, increased absolute low frequency (LFµs2; representing increased sympathetic nervous system (SNS) activity) was found in asthmatics who used β-agonist medication compared to those who did not (median: 1611, IQR 892–3036 vs 754, 565–1592; p < 0.05) and increased normalized low frequency (LF nu) was found in those with AHR compared to without AHR (64, 48–71 vs 53, 43–66; p < 0.05). Conclusion ANS activity (as measured using HRV analysis) is not associated with pathophysiology or inflammatory phenotype in young asthmatics with generally well-controlled asthma. However, enhanced SNS activity can be detected in asthmatics with AHR or who use β-agonist medication.

Heart Rate Variability Is Not Associated with Altered Emotional Modulation of Pain or Spinal Nociception.

Heart rate variability (HRV) is a physiological measure of beat-to-beat variation in time between heartbeats that reflects competing influences of the sympathetic and parasympathetic branches of the autonomic nervous system (ANS). Research suggests that both ANS branches, and consequently, HRV, are regulated by the central autonomic network (CAN), a widely distributed and interconnected circuit of cortical, limbic, and brainstem areas that modulate ANS activity to meet environmental demands based on current internal physiological conditions. Given its role in modifying internal states, the CAN has been implicated as an important circuit in emotion regulation, and previous researchers have hypothesized that HRV may be a physiological marker related to emotion regulation ability. Indeed, low HRV has been associated with disorders characterized by emotion dysregulation (i.e., depressive and anxiety disorders.) Thus, the current study was conducted to determine whether HRV (calculated using the root mean square of successive differences [RMSSD] and autoregressive high frequency spectral power), divided into tertiles reflecting low, medium, and high levels of HRV, was associated with altered emotional modulation of pain or spinal nociception (assessed from the nociceptive flexion reflex, NFR) during and emotional picture-viewing paradigm known as emotional controls of nociception (ECON). The sample was comprised of 261 healthy, pain-free men and women. It was hypothesized that low HRV would be associated with altered emotional modulation of pain/NFR relative to the other tertile groups for both measures of HRV, with greater facilitation of pain/NFR during negatively valenced pictures and impaired inhibition of pain/NFR during positively valenced pictures. Multilevel modeling analyses revealed that emotional modulation of pain and spinal nociception were not moderated by HRV. Thus, HRV does not appear to promote amplification of pain and nociception via emotional processes, at least not in healthy individuals. These research results were supported by a grant titled, "Native American Pain Disparities: Exploring Nociceptive Processing Differences" (Project Number: 1R01MD007807-01).

Location of Parasympathetic Innervation Regions From Electrograms to Guide Atrial Fibrillation Ablation Therapy: An in silico Modeling Study.

The autonomic nervous system (ANS) plays an essential role in the generation and maintenance of cardiac arrhythmias. The cardiac ANS can be divided into its extrinsic and intrinsic components, with the latter being organized in an epicardial neural network of interconnecting axons and clusters of autonomic ganglia called ganglionated plexi (GPs). GP ablation has been associated with a decreased risk of atrial fibrillation (AF) recurrence, but the accurate location of GPs is required for ablation to be effective. Although GP stimulation triggers both sympathetic and parasympathetic ANS branches, a predominance of parasympathetic activity has been shown. This study aims was to develop a method to locate atrial parasympathetic innervation sites based on measurements from a grid of electrograms (EGMs). Electrophysiological models representative of non-AF, paroxysmal AF (PxAF), and persistent AF (PsAF) tissues were developed. Parasympathetic effects were modeled by increasing the concentration of the neurotransmitter acetylcholine (ACh) in randomly distributed circles across the tissue. Different circle sizes of ACh and fibrosis geometries were considered, accounting for both uniform diffuse and non-uniform diffuse fibrosis. Computational simulations were performed, from which unipolar EGMs were computed in a 16 × 1 6 electrode mesh. Different distances of the electrodes to the tissue (0.5, 1, and 2 mm) and noise levels with signal-to-noise ratio (SNR) values of 0, 5, 10, 15, and 20 dB were tested. The amplitude of the atrial EGM repolarization wave was found to be representative of the presence or absence of ACh release sites, with larger positive amplitudes indicating that the electrode was placed over an ACh region. Statistical analysis was performed to identify the optimal thresholds for the identification of ACh sites. In all non-AF, PxAF, and PsAF tissues, the repolarization amplitude rendered successful identification. The algorithm performed better in the absence of fibrosis or when fibrosis was uniformly diffuse, with a mean accuracy of 0.94 in contrast with a mean accuracy of 0.89 for non-uniform diffuse fibrotic cases. The algorithm was robust against noise and worked for the tested ranges of electrode-to-tissue distance. In conclusion, the results from this study support the feasibility to locate atrial parasympathetic innervation sites from the amplitude of repolarization wave.

Diving Responses in Experienced Rebreather Divers: Short-Term Heart Rate Variability in Cold Water Diving.

IntroductionTechnical diving is very popular in Finland throughout the year despite diving conditions being challenging, especially due to arctic water and poor visibility. Cold water, immersion, submersion, hyperoxia, as well as psychological and physiological stress, all have an effect on the autonomic nervous system (ANS).Materials and methodsTo evaluate divers’ ANS responses, short-term (5 min) heart rate variability (HRV) during dives in 2–4°C water was measured. HRV resting values were evaluated from separate measurements before and after the dives. Twenty-six experienced closed circuit rebreather (CCR) divers performed an identical 45-meter decompression dive with a non-physical task requiring concentration at the bottom depth.ResultsActivity of the ANS branches was evaluated with the parasympathetic (PNS) and sympathetic (SNS) indexes of the Kubios HRV Standard program. Compared to resting values, PNS activity decreased significantly on immersion with face out of water. From immersion, it increased significantly with facial immersion, just before decompression and just before surfacing. Compared to resting values, SNS activity increased significantly on immersion with face out of water. Face in water and submersion measures did not differ from the immersion measure. After these measurements, SNS activity decreased significantly over time.ConclusionOur study indicates that the trigeminocardiac part of the diving reflex causes the strong initial PNS activation at the beginning of the dive but the reaction seems to decrease quickly. After this initial activation, cold seemed to be the most prominent promoter of PNS activity – not pressure. Also, our study showed a concurrent increase in both SNS and PNS branches, which has been associated with an elevated risk for arrhythmia. Therefore, we recommend a short adaptation phase at the beginning of cold-water diving before physical activity.

Screening of Pathophysiological Mechanisms and Psychological and Occupational Factors, Determining Risk of Cardiovascular Diseases in High-Risk Professions

Abstract Cardiovascular diseases (CVD) are among the most significant and common chronic non-communicable diseases in Bulgaria. Screening, identification and registration of pathophysiological mechanisms and psychological and occupational factors related to CVD should be implemented in the diagnostic work-up. Job analysis contributes to the implementation of screening and identification of the most significant psychological and professional factors related to the work activity. Aim: The aim of our study is to examine the pathophysiological mechanisms of autonomic cardiovascular control and psychological and occupational factors determining the risk of CVD. Materials and methods: The following groups of individuals were examined: 83 physicians, 54 nurses, 23 employees and 40 militaries. The autonomic cardiovascular control was studied through the time-and frequency-domain based measures of the Analysis of Heart Rate Variability (HRV). Results: The results of the ANOVA test showed that there was a statistically significant difference in the time-domain and frequency-domain based HRV measures between the compared groups: X [F (4; 225) = 4.455, p = 0.001]; SDNN [F (4; 225) = 3.876, p = 0.005]; SDNN5 [F (4; 225) = 3.083, p = 0.01]; pNN50 [F (4; 225) = 8.303, p &lt; 0.001]; rMSSD [F (4; 225) = 8.711, p &lt; 0.001]; SDSD [F (4; 225) = 8.323, p &lt; 0.001; VLF [F (4; 225) = 1.204, p = 0.31]; LF [F (4; 225) = 3.874, p = 0.005]; HF [F (4; 225) = 7.790, p &lt; 0.001] and LF/HF [F (4; 225) = 8.601, p &lt; 0.001]. The results of our study revealed that occupational stress and cognitive workload in physicians, nurses, and employees induced a process of reciprocally combined inhibition of the parasympathetic branch of the autonomic nervous system (ANS) (SDNN, SDNN5, pNN50, rMSSD, and HF) and activation of the sympathetic branch of ANS (LF), while in military personnel they cause a process of co-activation of the parasympathetic and sympathetic branches of the ANS (rMSSD, SDNN, SDNN5, pNN50 and LF/HF). Conclusion: Stress-induced dysfunctional autonomic cardiovascular regulation, patho-physiological control mechanisms, psychological and occupational factors determine the risk of CVD. Their identification could contribute to the diagnostics and prevention of CVD.

A latent change score approach to understanding dynamic autonomic coordination.

Children's self-regulation is a core adaptive system in child development. Physiological indices of regulation, particularly the autonomic nervous system (ANS), have garnered increased attention as an informative level of analysis in regulation research. Cardiography supports the simultaneous examination of both ANS branches via measures of pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA) as indicators of sympathetic and parasympathetic activity, respectively. However, despite their heavily intertwined functions, research examining autonomic coordination across sympathetic and parasympathetic systems is scarce. Moreover, extant efforts have favored static, mean level reactivity analyses, despite the dynamic nature of ANS regulation and the availability of analytic tools that can model these processes across time. This study drew on a sample of 198 six-year-old children from a diverse community sample (49.5% female, 43.9% Latinx) to examine dynamic autonomic coordination using bivariate latent change score modeling to evaluate bidirectional influences of sympathetic and parasympathetic activity over the course of a challenging puzzle completion task. Results indicated that children evidenced reciprocal sympathetic activation (i.e., PEP attenuation and RSA withdrawal) across the challenge task, and these regulatory responses were characterized by a temporally leading influence of PEP on lagging changes in RSA. The current findings contribute to our understanding of children's autonomic coordination while illustrating a novel analytic technique to advance ongoing efforts to understand the etiology and developmental significance of children's physiological self-regulation.

Defining Cardiac Dysautonomia - Different Types, Overlap Syndromes; Case-based Presentations.

The cardiovascular branch of autonomic nervous system (ANS) is responsible for the regulation of heart rate, blood pressure, and maintaining homeostasis during physiological stress such as exercise and standing upright. ANS constantly controls the rate and force of heart contractions and the vascular tone with the aim to maintain the sufficient tissue perfusion with oxygenated blood and secure venous return to the heart. Dysautonomias, result of ANS malfunction, are often found in patients with cardiovascular symptoms. Apart from the most prevalent one, arterial hypertension, the cardiovascular dysautonomic continuum encompasses other important although less known conditions: postural orthostatic tachycardia syndrome, inappropriate sinus tachycardia, orthostatic hypotension and reflex syncope. Moreover, heart diseases may evoke autonomic imbalance by themselves; cardiac pump failure is usually associated with sympathetic hyperactivity, neuroendocrine vasopressor activation, higher heart rate, reduced heart rate variability and baroreflex hyposensitivity, all of which are predictors of adverse outcomes. Cardiologists and electrophysiologist frequently see patients for the evaluation and management of unexplained syncope, orthostatic intolerance, heart rhythm abnormalities and symptoms of palpitations. Recognizing the presence of cardiac dysautonomia is an important skill which is necessary for the appropriate evaluation and treatment of these patients. Clinical presentations may overlap, and the importance of a thorough history cannot be over-emphasized. In this review we will present a cases of a patients with cardiac dysautonomia which is illustrative of a typical patient experience, followed by a review of the autonomic nervous system and discussion of prevalence, clinical presentation, and pathophysiology of common cardiac dysautonomias.

Creative Flow and Physiologic States in Dancers During Performance.

Pre-professional and professional dancers (n = 60) participated in this ambulatory psychophysiology study that investigated performance flow and heart rate and autonomic nervous system (ANS) function during three time periods: baseline rest, performance, and post-performance rest. To gather these results, the psychophysiology laboratory traveled to the concert hall to collect data on dancers. The self-report Flow State Scale (FSS) measured global flow, challenge–skill balance, sense of control, and autotelic experiences; it addresses important features of the creative experience of performing artists. These data were collected immediately following the performance. The flow measures were compared with physiologic responses to performance [heart rate, pre-ejection period (PEP), root mean square differences of successive R-R (heartbeat) intervals (RMSSD), cardiac autonomic balance, and cardiac autonomic regulation]. The regression analyses indicated that greater sympathetic nervous system (SNS) activation with performance (PEP change from base to performance) explained 8.8% of the variance in sense of control, whereas less cardiac autonomic regulation explained 13.8% of the variance in autotelic experiences. The sample was then divided into high and low flow groupings and four autonomic groups. During performance, the high autotelic group and high sense of control group had a higher distribution of dancers with co-inhibition of both ANS branches than had the low autotelic and sense of control groups who employed more co-activation of both ANS branches (chi-square analyses). These novel findings add to the growing information about the interaction of both branches of the ANS during creative performance flow states.

Effect of Different ECG Leads on Estimated R-R Intervals and Heart Rate Variability Parameters.

Heart rate and heart rate variability parameters provide important information on sympathetic and parasympathetic branches of autonomous nervous system. These parameters are usually extracted from electrocardiograms often measured between two electrodes and called an ECG lead. Besides systems intended only for heart rate measurement, ECG measurement devices employ several well-known lead systems including the standard 12-lead system, EASI lead system and Mason-Likar systems. Therefore, the first step is to select the appropriate lead for heart rate variability analysis. The appropriate electrode locations for single-lead measurement systems or the preferred measurement lead in multi-lead measurement are choices that the user needs to make when the heart rate variability is of interest. However, it has not been addressed in the literature, if the lead selection has an effect on the obtained HRV parameters. In this work, we characterized the amount of deviation of heart rate and heart rate variability parameters extracted from nine ECG leads, six from EASI leads and three modified limb leads. The results showed a deviation of 2.04, 2.88, 2.06 and 3.45 ms in SDNN, rMSSD, SD1 and SD2, respectively. A relative difference up to 10% was observed in HRV parameters for single signal frames. Additionally, the discrimination of the R-peaks by amplitudes was evaluated. The A-S lead appeared to have the best performance in all the tests.

Pupillary Light Reflex in Children with ADHD

Abstract Attention deficit/hyperactivity disorder (ADHD) is one of the most frequently seen mental disorders in children with an increasing risk for other mental disorders. ADHD represents a primary biological dysfunction of the central nervous system, such as dysregulation of frontal-subcortical-cerebellar catecholaminergic circuits and imbalances in the dopaminergic system. However, autonomic nervous system, comprised of two primary branches - sympathetic and parasympathetic nervous systems that are normally in dynamic balance, plays an essential role in the regulation of body functions. Although it is generally assumed that the autonomic regulation is impaired during ADHD the information related to this dysregulation is limited. One of the options to observe changes of autonomic balance in ADHD is pupillary light reflex (PLR). Pupillometric evaluation can be used for the assessment of functioning of both autonomic nervous system branches and certain parameters of pupil responsivity can be helpful as a tool for medical diagnostic and treatment. In conclusion, these findings suggest the pupillometry as a non-invasive method that can indicate abnormalities in the complex central autonomic network regulating PLR.

Testing the vagal withdrawal hypothesis during light exercise under autonomic blockade: a heart rate variability study.

We performed the first analysis of heart rate variability (HRV) at rest and during exercise under full autonomic blockade on the same subjects, to test the conjecture that vagal tone withdrawal occurs at exercise onset. We hypothesized that between rest and exercise there would be 1) no differences in total power (PTOT) under parasympathetic blockade, 2) a PTOT fall under β1-sympathetic blockade, and 3) no differences in PTOT under blockade of both autonomic nervous system branches. Seven men [24 (3) yr, mean (SD)] performed 5-min cycling (80 W) supine, preceded by 5-min rest during control and with administration of atropine, metoprolol, and atropine + metoprolol (double blockade). Heart rate and arterial blood pressure were continuously recorded. HRV and blood pressure variability were determined by power spectral analysis, and baroreflex sensitivity was determined by the sequence method. At rest, PTOT and the powers of low- and high-frequency components of HRV (LF and HF, respectively) were dramatically decreased with atropine and double blockade compared with control and metoprolol, with no effects on LF-to-HF ratio and on the normalized LF (LFnu) and HF (HFnu). During exercise, patterns were the same as at rest. Comparing exercise with rest, PTOT varied as hypothesized. For systolic and diastolic blood pressure, resting PTOT was the same in all conditions. During exercise, in all conditions, PTOT was lower than in control. Baroreflex sensitivity decreased under atropine and double blockade at rest and under control and metoprolol during exercise. The results support the hypothesis that vagal suppression determined disappearance of HRV during exercise.NEW & NOTEWORTHY This study provides the first demonstration, by systematic analysis of heart rate variability at rest and during exercise under full autonomic blockade on the same subjects, that suppression of vagal activity is responsible for the disappearance of spontaneous heart rate variability during exercise. This finding supports previous hypotheses on the role of vagal withdrawal in the control of the rapid cardiovascular response at exercise onset.

Role of AT1 receptor‐mediated ADAM17 signaling in glutamatergic neurons in neurogenic hypertension

Using a mouse model with Angiotensin II type 1 receptor (AT1R) deletion from neurons in the central nervous system, we previously reported attenuated hypertension, improved autonomic function, and importantly, blunted A Disintegrin And Metalloprotease 17 (ADAM17) activation after deoxycorticosterone‐salt treatment (DOCA 1 mg/g body weight sc + 1% saline po for 3 weeks), compared to non‐transgenic controls. Since neuronal AT1aR has a pivotal role in ADAM17‐mediated ACE2 shedding and the maintenance of neurogenic hypertension, we further investigated the role of central AT1R‐mediated ADAM17 signaling in excitatory neurons, by deleting AT1aR (AT1G) or ADAM17 (A17G) specifically from glutamatergic neurons. AT1G (n=9), A17G (n=8), and controls (n=10) were implanted with telemetry probes for continuous recording of blood pressure (BP). Following DOCA‐salt treatment, all 3 strains showed increased mean arterial pressure, however the pressor responses were significantly lower in both transgenic lines (AT1G: +16 ±3 mmHg, A17G: +21 ±3 mmHg), compared to the controls (+31 ±2 mmHg). Meanwhile, DOCA‐salt treated controls (n=9) exhibited a significant decrease in cardiac systolic function, including ejection fraction (P&lt;0.01 vs. sham) and fractional shortening (P&lt;0.05 vs. sham). Cardiac systolic function remained unchanged in both DOCA‐salt‐treated AT1G (n=9) and A17G (n=5). By the end of DOCA‐salt treatment, baroreflex sensitivity was markedly blunted in the controls (P&lt;0.01 vs. sham), while it was attenuated in A17G (P&lt;0.05 vs. control+DOCA) and completely preserved in AT1G. Baroreflex mediated BP regulation requires both branches of autonomic nervous system. Therefore, sympathetic and parasympathetic tone were assessed in the following experiment. DOCA‐salt‐induced increase in cardiac sympathetic tone was not observed in either AT1G or A17G. Also, vascular sympathetic tone, which can be upregulated in DOCA‐salt hypertension, exhibited no significant change in mice lacking glutamatergic AT1aR or ADAM17. DOCA‐salt‐induced impairment in cardiac vagal tone was still observed in A17G mice (P&lt;0.05 vs. sham), but not in AT1G. Moreover, in AT1G mice, the cardiac vagal tone was found to be significantly upregulated after DOCA‐salt treatment. Intracerebroventricular injection of PD123319, an AT2R antagonist, blocked the excessive vagal tone in DOCA‐salt treated AT1G mice (n=3), suggesting that removal of AT1R from glutamatergic neurons could unmask AT2R signaling. Through mouse blood panel analysis, we found that peripheral immune system was activated during DOCA‐salt hypertension, indicated by increased CD3+, CD45+ and CD3+/CD45+ cell counting. Interestingly, the increased immune cell counting was attenuated in DOCA‐salt treated AT1G and A17G mice. Whether this is due to controlled sympathetic outflow, or it is a secondary to attenuated hypertension, still requires further investigation. In summary, our data provide evidence that AT1aR located on glutamatergic neurons regulate autonomic function and the development of hypertension through ADAM17‐dependent and independent pathways.Support or Funding InformationNIH: HL093178; AHA: 15POST25000010This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Gender-specific response to acute mental stress assessed by heart rate variability

Background: Long-standing stress is an important risk factor for many diseases. Certain diseases are found to be associated with males than females. This difference may be due to the variation in the reactivity to stress exhibited by both the sexes which we assessed in the present study. The responses during stress are mediated partly by sympathetic and parasympathetic branches of autonomic nervous system (ANS). Heart rate variability (HRV) is a simple and non-invasive tool to study ANS. HRV can be analyzed by time domain and frequencydomain methods. The HRV in males and females during mental stress test may point to their disparity in autonomic response to stress and hence the predisposition to various diseases. Aim and Objective: The objective of this study was to assess the autonomic activity in males and females at rest and during mental stress test using HRV. Materials and Methods: There were 12 males and 18 females in the study who were selected based on inclusion and exclusion criteria. Mental arithmetic test is used to induce mental stress. HRV was calculated during baseline condition and mental stress test. Square root of the mean squared differences of successive NN intervals (RMSSD) and standard deviation of average NN intervals are the variables used in time domain analysis of HRV. Low-frequency (LF), high-frequency (HF), and LF/HF were used under frequency domain analysis. Results: There was a statistically significant difference in RMSSD during mental stress test. None of the other variables did not show any difference between two groups at rest and also during mental stress test. Conclusion: Less HRV in males during mental stress test indicates a shift of autonomic balance toward sympathetic activity in them. This shows that they are more predisposed to complications associated with stress.

Gastric distension causes changes in heart rate and arterial blood pressure by affecting the crosstalk between vagal and splanchnic systems in anesthetised rats.

Various hindbrain nuclei have been demonstrated to be involved in the control of the cardiovascular reflexes elicited by both non-noxious and noxious gastric distension, through parasympathetic and sympathetic activation. The different role played by the branches of autonomic nervous system in exerting these effects and their crosstalk in relation to low-/high-pressure distension rate has not been examined yet. Therefore, in the present work, monolateral and bilateral vagotomy and splanchnicotomy were performed in anesthetised rats to analyse the involvement of hindbrain nuclei in haemodynamic changes caused by gastric distension at high (80mmHg) and low (15mmHg) pressure. The analysis of c-Fos expression in neuronal areas involved in cardiovascular control allowed us to examine their recruitment in response to various patterns of gastric distension and the crosstalk between vagal and splanchnic systems. The results obtained show that the low-pressure (non-noxious) gastric distension increases both heart rate and arterial blood pressure. In addition, the vagus nerve and hindbrain nuclei, such as nucleus ambiguous, ventrolateral medulla and lateral reticular nucleus, appear to be primarily involved in observed responses. In particular, we have found that although vagus nerve plays a central role in exerting those cardiovascular reflex changes at low gastric distension, for its functional expression an intact splanchnic system is mandatory. Hence, the absence of splanchnic input attenuates pressor responses or turns them into depressor responses. Instead at high-pressure (noxious) gastric distension, the splanchnic nerve represents the primary component in regulating the reflex cardiovascular effects.

Heart rate independent QT variability component can detect subclinical cardiac autonomic neuropathy in diabetes.

Cardiac autonomic neuropathy (CAN) may lead to life threatening arrhythmia due to denervation of both the parasympathetic and sympathetic branches of autonomic nervous system innervating the heart. CAN is a frequently under diagnosed complication of diabetes, because a patient can have asymptomatic CAN for several years before it is clinically apparent. However, detection of CAN at the early or subclinical stage leads to more effective treatment outcomes. Cardiac autonomic reflex tests (CART) (i.e. Ewing test battery) are normally used for the detection and staging of CAN. These tests have limitations with the necessity of active participation of the patients for test maneuvers, as a majority of patients will not be able to complete all five tests required due to comorbidities such as frailty, obesity or cardiorespiratory disease. CAN affects both heart rate (measured by RR interval dynamics) and ventricular repolarization function (i.e. QT interval dynamics) of the heart, which can be efficiently analyzed from surface ECG. Therefore, ECG based diagnosis techniques of CAN analysis are becoming popular as they can reduce the limitations of CARTs used traditionally for CAN detection and it complements CART results. In this study, the performance of an ECG based QTV feature derived using a model free approach, which can quantify the QTV component not affected directly by the heart rate (HR) variation, is compared with some other measures of QTV and HRV in subclinical CAN detection in diabetes. Short-term ECGs (i.e. 5 min long) of 60 diabetic subjects without CAN and 50 diabetic subjects detected with early level of CAN determined by CART were analyzed. The proposed measure for quantifying the QTV component independent of HR denoted as QTV~RR stands out to be more discriminatory than other existing variability measures of QTV and HRV in subclinical detection of CAN.

Disentanglement of sympathetic and parasympathetic activity by instantaneous analysis of human heartbeat dynamics.

Spectral analysis of heart rate variability (HRV) is one of the most effective techniques for the assessment of the influence of the autonomic nervous system (ANS) on the heartbeat. Despite its widespread use, it has been demonstrated that HRV subdivision in the low frequency (LF) and high frequency (HF) bands does not accurately reflect separate sympathetic and parasympathetic influences, respectively, mainly due to overlap of the two branches in the low frequencies. Here we propose two novel indices, namely the instantaneous sympathetic autonomic index (SAI) and parasympathetic autonomic index (PAI), that are able to separately assess the time-varying ANS synergic functions. The application of the paradigm is presented here by associating proper combinations of orthonormal Laguerre functions defined within the heartbeat point-process continuous model. Preliminary results from ten subjects recorded during a tilt-table protocol show that the proposed methodology, differently than the traditional spectral parameters, is able to separately track the independent changes associated with the two ANS branches.