Lower Parasympathetic Tone Research Articles

Phenotypes of COVID-19-associated dysautonomia in patients requiring veno-venous extracorporeal membrane oxygenation

Background. Patients with novel coronavirus infection (COVID-19) receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) are typically prone to hemodynamic disorders of various severity. Tachycardia, increased cardiac output, or arterial hypotension affect the effectiveness of VV-ECMO. One of the possible causes of hemodynamic disorders leading to ineffective VV-ECMO may be dysautonomia (DA), which refers to an imbalance of sympathetic and parasympathetic divisions of the autonomic nervous system (ANS). The development of DA in various critical conditions was described previously. Dysautonomia also develops in COVID-19 (COVID-19-associated DA), but it was studied only in stable non-ICU patients. The presented study focuses on COVID-19-associated DA in critical COVID-19 patients requiring VV-ECMO support. The study was aimed at determining COVID-19-associated DA phenotypes, their impact on VV-ECMO effectiveness and disease outcomes. Materials and methods. The study included 20 patients: 12 (60%) females, 8 (40%) males. The patients had an average age of 55 years. All the patients underwent 24-hour Holter monitoring with spectral analysis of heart rate variability (HRV) assessing low-frequency component of the spectrum (LF), the high-frequency component of the spectrum (HF), the LF/HF ratio on days 1, 3, and 5 of VV-ECMO. Diagnostic criteria for COVID-19-associated DA was a decrease in LF/HF 2.28 or an increase in LF/HF 6.94. The diagnostic criteria of predominant tone of sympathetic nervous system (sympathetic tone) was an increase in LF/HF 6.94, while a decrease in LF/HF 2.28 indicated predominant parasympathetic tone. Low sympathetic tone was determined by a decrease in LF 15%, and an increase in LF 40%. Low parasympathetic tone was determined by a decrease in HF 15%, and an increase in HF 25%. The criteria used were based on the results of previous studies. The following parameters were registered in the study population: VV-ECMO weaning, duration of respiratory and VV-ECMO support, length of stay in the intensive care unit (ICU) and in hospital, and disease outcomes. Results. COVID-19-associated DA was diagnosed in all the patients. LF/HF median value was 0.1. HRV spectrum parameters changed significantly over time: on day 5 of VV-ECMO support LF and HF values significantly decreased. The patients were divided into three groups according to the DA phenotype: group 1 (n = 4 [20%]) with normal sympathetic tone and high parasympathetic tone (nShP phenotype); group 2 (n = 14 [70%]) with low sympathetic tone and high parasympathetic tone (lShP phenotype); group 3 (n = 2 [10%]) with low sympathetic tone and normal parasympathetic tone (lSnP phenotype). The latter group was excluded from further statistical analysis due to the small sample size. In group 2, the mean HR was significantly higher compared with group 1. In group 1, VV-ECMO weaning was successful in 50% of cases, whereas in group 2 it was successful in 7.2% (p = 0.04). Conclusions. To determine a dysautonomia phenotype, it is necessary to continuously monitor DA status in COVID-19 patients during VV-ECMO. Tachycardia in COVID-19 patients during VV-ECMO does not exclude the ANS imbalance with a significant predominance of parasympathetic tone over the sympathetic tone. It is this COVID-19-associated DA phenotype that is significantly associated with the unfavorable outcomes.

Mind and body connection in expert meditators: a computational study based on central and peripheral nervous system

A meditative ‘technique’ is conceived as a continuum of different affective states involving mind and body jointly. Meditative practices can involve cognitive effort (e.g., focused attention and open-minded techniques), as well as automatic and implicit practices (e.g., transcendental techniques). The NGALSO tantric self-healing meditation technique is a brief, comprehensive meditation technique relying on mind and body connection. In this study, we aimed to investigate the state and the trait neurophysiological correlates of NGALSO meditation practice. First, 19 EEG channels and a 3-lead ECG signal were recorded from 10 expert meditators (more than 7 years of daily meditation) and 10 healthy inexpert participants (controls) who underwent the same meditative procedure. The neuropsychological profiles of experts and controls were compared. Results showed that expert meditators had significantly higher power spectra on alpha, theta and beta, and a higher sympathetic tone with lower parasympathetic tone after meditation. Conversely, the control group had significantly less power spectra on alpha, theta and beta, and a higher parasympathetic tone with lower sympathetic tone after meditation. A machine learning approach also allowed us to classify experts vs. controls correctly by using only EEG Theta bands before or after meditation. ECG results allowed us to show a significantly higher effort by expert meditators vs. controls, thus suggesting that a higher effort is required for this meditation, in line with the principle ‘no pain, no gain’ in body and mind.

Exercise-induced neuroplasticity in autonomic nuclei restores the cardiac vagal tone and baroreflex dysfunction in aged hypertensive rats.

Aging is accompanied by considerable deterioration of homeostatic systems, such as autonomic imbalance characterized by heightened sympathetic activity, lower parasympathetic tone, and depressed heart rate (HR) variability, which are aggravated by hypertension. Here, we hypothesized that these age-related deficits in aged hypertensive rats can be ameliorated by exercise training, with benefits to the cardiovascular system. Therefore, male 22-mo-old spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto (WKY) submitted to moderate-intensity exercise training (T) or kept sedentary (S) for 8 wk were evaluated for hemodynamic/autonomic parameters, baroreflex sensitivity, cardiac sympathetic/parasympathetic tone and analysis of dopamine β-hydroxylase (DBH+) and oxytocin (OT+) pathways of autonomic brain nuclei. Aged SHR-S versus WKY-S exhibited elevated mean arterial pressure (MAP: +51%) and HR (+20%), augmented pressure/HR variability, no cardiac vagal tone, and depressed reflex control of the heart (HR range, -28%; gain, -49%). SHR-T exhibited a lower resting HR, a partial reduction in the MAP (-14%), in the pressure/HR variabilities, and restored parasympathetic modulation, with improvement of baroreceptor reflex control when compared with SHR-S. Exercise training increased the ascending DBH+ projections conveying peripheral information to the paraventricular nucleus of hypothalamus (PVN), augmented the expression of OT+ neurons, and reduced the density of DBH+ neurons in the rostral ventrolateral medulla (RVLM) of SHR-T. Data indicate that exercise training induces beneficial neuroplasticity in brain autonomic circuitry, and it is highly effective to restore the parasympathetic tone, and attenuation of age-related autonomic imbalance and baroreflex dysfunction, thus conferring long-term benefits for cardiovascular control in aged hypertensive individuals.NEW & NOTEWORTHY Exercise training reduces high blood pressure and cardiovascular autonomic modulation in aged hypertensive rats. The dysfunction in the baroreflex sensitivity and impaired parasympathetic tone to the heart of aged hypertensive rats are restored by exercise training. Exercise induces beneficial neuroplasticity in the brain nuclei involved with autonomic control of cardiovascular function of aged hypertensive rats.

EXPRESS: Plasma endocannabinoids and cannabimimetic fatty acid derivatives are altered in cyclic vomiting syndrome: The effects of sham feeding.

Cyclic vomiting syndrome (CVS) is an underdiagnosed disorder of the gut-brain interaction. Our understanding of the pathophysiology of CVS is evolving. Here, we tested the hypotheses that: (1) the levels of endocannabinoids and related lipids are altered in CVS, and (2) cephalic-vagal stimulation drive changes in endolipid levels. Ten adult patients with CVS and 8 healthy controls were included. Indirect measurements of parasympathetic (RFa) functions were performed with spectral analysis of heart rate variability and respiratory activity. Plasma levels of endocannabinoids and related lipids were measured at baseline and during a sham feeding. Values are reported as mean ± SEM and compared using t-test or ANONA. CVS patients had a lower parasympathetic tone and response to Valsalva maneuver and deep breathing than the controls. The baseline 2-Arachidonoylglycerol (2-AG) had a significantly higher concentration in CVS (5.9e-008 ± 3.7e-008 mole/L) than control (3.7e-008 ± 1.3e-008 mole/; p<0.05). Sham feeding did not change the concentration of 2-AG. 2-linoleoylglycerol and 2-oleoylglycerol were significantly higher in CVS than control and did not change with sham feeding. Levels of N-acyl ethanolamines, including Anandamide (AEA), were not different in CVS vs. control. After sham feeding, AEA showed a trend toward increasing (P=0.08) in CVS, but not in control. With sham feeding, palmitoyl ethanolamine significantly increased in both CVS and control groups; oleoyl ethanolamine in CVS only, and stearoyl ethanolamine in the control group. Levels of endocannabinoids and related lipids are altered in CVS patients. Sham feeding affects endogenous signaling lipids in a disease and time-dependent manner.

289 Heart Rate Variability in Opioid Use Disordered Participants Undergoing Buprenorphine-Assisted Detoxification

OBJECTIVES/GOALS: This study explored whether gabapentin (GBN) differentially impacted heart rate variability (HRV) and whether HRV was associated with opioid withdrawal ratings among participants with opioid use disorder (OUD) undergoing a randomized, double blind placebo-controlled, trial (RCT) of GBN during a buprenorphine (BUP)-assisted taper. METHODS/STUDY POPULATION: Participants (ages 18-64) with OUD, no recent use of benzodiazepines/barbiturates, and no major psychiatric disorders or unstable medical conditions were enrolled in the RCT, inducted onto BUP starting week 1 day 1 and randomly assigned to receive adjunct GBN or placebo starting week 1 day 3. All participants began a 10-day BUP-taper beginning week 2 day 3. HRV measures were assessed on week 1 day 2 (before GBN/placebo induction), week 2 day 2, and week 3 day 5 (end of BUP taper). HRV metrics were analyzed using Two Sample T-Test to determine differences between GBN vs. Placebo. Correlations between HRV metrics and opioid withdrawal ratings administered at the above timepoints will be analyzed using Spearman correlation. RESULTS/ANTICIPATED RESULTS: 28 participants underwent at least 1 HRV session that resulted in usable data. Preliminary statistical analyses revealed that HRV trended lower for GBN subjects during PB exercises than Placebo subjects, demonstrated by a higher mean heart rate for GBN subjects compared to Placebo subjects (p=0.0506) at the end of the BUP-taper (week 3 day 5). We expect future analyses to demonstrate a negative correlation between certain HRV metrics indicative of parasympathetic tone and opioid withdrawal rating assessment scores indicative of withdrawal severity. Such findings would demonstrate an association between opioid withdrawal severity and lower parasympathetic tone and HRV. DISCUSSION/SIGNIFICANCE: Individuals with OUD have previously been shown to have a lower parasympathetic tone than individuals without OUD. Additionally, opioid withdrawal has been shown to be associated with reduced parasympathetic tone. Our initial findings suggest that adjunct GBN administration was not associated with lower parasympathetic tone during PB exercises.

Maternal Weight Gain during Pregnancy and the Developing Autonomic Nervous System—Possible Impact of GDM

The intrauterine environment is known to affect the offspring's long-term risk for obesity and diabetes. Previous data show that maternal metabolism and gestational weight gain (GWG) are associated with fetal autonomic nervous system (ANS) function, which can be assessed with heart rate variability (HRV). We investigated whether this association is also present in 2-year-old children and addressed the impact of gestational diabetes (GDM). We examined the 2-year-old offspring of mothers who had undergone a 5-point, 75 g oral glucose tolerance test during pregnancy. To assess HRV, a 10-minute ECG was recorded, and time domain and frequency domain parameters were analyzed. Body composition was assessed using bioelectrical impedance testing. We examined 67 children (33 girls, 34 boys), 30 of whom were born to mothers with treated GDM and normoglycemic pregnancies (NGT), respectively. No differences were found between the groups with regard to birth weight, weight at the age of 2 years, and body fat content. We observed that GWG was associated with heart rate and HRV, indicating that children of mothers with low GWG had a lower parasympathetic tone. This association was detected in NGT-exposed-but not in GDM-exposed-children. HR and HRV correlated with body fat and fat-free mass in children from normoglycemic pregnancies only. We found that the impact of maternal GWG on offspring ANS function was missing in the presence of treated GDM. The balance of the ANS was related to offspring body composition in children from NGT pregnancies only. Our results suggest that maternal weight gain during pregnancy has a critical impact on the developing ANS, which might be disturbed in the presence of GDM.

Autonomic measures identify stress, pain, and instability associated with retinopathy of prematurity ophthalmologic examinations.

Retinopathy of prematurity (ROP) ophthalmologic examinations cause stress and pain. Infants' stress and pain can be measured non-invasively using skin conductance (SC) and high frequency heart rate variability (HF-HRV), reflecting sympathetic-mediated sweating and parasympathetic activity, respectively. To test the utility of SC to detect sympathetic activation during ROP examination, and the contribution of HF-HRV to predict stability post-examination. In this prospective, single center study, we measured SC continuously pre-, during, and post-examination, and HRV at 24 h pre-ROP examination. Clinical data included stability [apneas, bradycardias, and desaturations (A/B/Ds)], and interventions post-examination. SC increased 56% above baseline during ROP examination (p = 0.001) and remained elevated post-examination (p = 0.02). Post-hoc analysis showed higher illness acuity, represented by need for respiratory support, was associated with lower HF-HRV at 24 h pre-ROP examination (p = 0.001). Linear regression indicated lower HF-HRV at 24 h pre-examination contributed to the need for higher intervention (i.e., stimulation to breathe, oxygen support) particularly among infants with higher illness acuity [F(1, 15) = 5.05, p = 0.04; β = -1.33, p = 0.04]. ROP examination induced a 2-fold increase in sympathetic activation which remained above baseline in recovery. Also, we propose that the low parasympathetic tone associated with autonomic imbalance contributes to instability and need for higher intervention to assure stabilization with A/B/D events. Our findings provide insight into the underestimation of adverse events associated with ROP examination and identification of infants who may be more vulnerable to potential sequelae following ROP examinations.

Abstract P112: Evidence Of Renin Expression And Function In The Brainstem

The role of the brain renin-angiotensin system (RAS) in blood pressure (BP) and autonomic control isrecognized. However, the lack of the precise source of renin in the brain is one of the main barrierstowards a complete understanding of how the brain RAS operates. Here, we hypothesized that renin isexpressed in brain regions involved in sympathetic control such as the rostroventral lateral medulla(RVLM). We employed RNAscope, a highly sensitive and specific in situ hybridization technology.Surprisingly, the renin positive signals were absent in the RVLM, but we identified renin transcripts inthe nucleus ambiguus (NA), a site in the vicinity of the RVLM that contains cardiac vagal motoneurons.There was no signal in this region with the negative control scrambled probe. The signal strength wasgreater than that observed in other regions of the brain classically associated with the brain RAS. Wealso observed that the NA contains other necessary RAS components to produce angiotensin.Interestingly, renin was colocalized with cells expressing choline acetyltransferase (ChAT), suggesting itspossible role in cholinergic neurotransmission. Therefore, we generated mice lacking renin specifically incholinergic neurons (Ren-a ChAT-null ). Because we previously identified an alternative brain-specific reninisoform (ren-b) that elicits cardioprotective roles, we also generated mice lacking ren-b in cholinergicneurons (Ren-b ChAT-null ). At baseline, Ren-a ChAT-null exhibited a trend towards decreased BP, while Ren-b ChAT-null exhibited higher BP, although these differences were not statistically significant. Importantly,Ren-a ChAT-null exhibited an attenuated tachycardiac and pressor responses to atropine (p&lt;0.005 andp&lt;0.05, respectively; n=4-7), indicating a lower parasympathetic tone in these mice. Conversely, Ren-b ChAT-null exhibited an augmented pressor response to atropine (p&lt;0.005; n=7) suggesting an elevatedparasympathetic tone. These data suggest that the activation of the brain RAS in the NA might play arole in cholinergic neurotransmission, and it defines the NA as a potential source of endogenous renin inthe brainstem. Studies to understand the differential contribution of Ren-a and Ren-b in the NA to BPare in progress.

Associations of Cancer-Related Fatigue with Autonomic and Sensorimotor Functions in Children Treated for Brain Tumors: an Observational Study

INTRODUCTION. Chronic fatigue syndrome is a condition, characterized by a severe fatigue that lasts continuously for more than 6 months and has a significant negative impact on the psychophysiological functions. Cancer-related fatigue is identified as an important symptom associated with cancer, associated with autonomic dysfunction. AIM. To reveal objective autonomic and neurodynamic indicators of the severity of CRF in children suffered of neuro-oncological diseases. MATERIAL AND METHODS. Children (8-17 years old) who were under dynamic observation after neuro-oncological diseases for more than six months (n=67) performed maximal tapping tasks, auditory-motor synchronization, and filled out the questionnaire «The Turkish Scale for the Assessment of Fatigue in Pediatric Oncology Patients Aged 7-18». Physiological indices (heart rhythm, peripheral temperature, skin conductance, breathing amplitude and frequency) were recorded at rest and during sensorimotor task. RESULTS AND DISCUSSION. The subscale “Sleep-related fatigue” positively correlates with the average frequency of maximum tapping and with the degree of its slowdown towards the end, which also correlates with the total score of the questionnaire. Statistically significant correlations of scores on the subscale “Subjective feelings of fatigue” with LF/HF and pNN50 at rest were revealed. The amplitude of thoracic respiration positively correlates with the scores of “Fatigue associated with daily activities”, “Subjective feeling of fatigue”, and the total score. Comparison of groups with a low and high total score of the questionnaire does not reveal statistically significant differences in the background indicators of heart rate variability, however, in the process of maximum tapping, the RMSSD and pNN50 indicators are higher, and the indicator of nonlinear heart rate analysis SD2/SD1 is lower in the group with low scores on the questionnaire. CONCLUSION. Children with cancer-related fatigue had reduced heart rate variability, lower parasympathetic tone and greater exhaustion during the tapping test. The combination of objective and subjective indicators reflects the dynamics of cancer-related fatigue and the rehabilitation process more reliably

1036-P: The Association between Maternal Gestational Weight Gain and Autonomic Nervous System Is Disturbed in GDM: Results from Two-Year-Old Children

Objective: The intrauterine environment is known to affect the offspring's long-term risk for obesity and diabetes. Previous data show that maternal metabolism and gestational weight gain (GWG) are associated with autonomic nervous system (ANS) function in fetuses in utero, which can be assessed with heart rate variability (HRV) . We have now examined whether this association is also present in 2-year-old children and addressed the impact of gestational diabetes (GDM) . Research Design and Methods: We examined children of participants of the ongoing PREG study (NCT04270578) who had a 5-point 75g oral glucose tolerance test during pregnancy. To assess HRV, a 10-minute ECG was recorded in the offspring. We analyzed time domain (beats per minute (BPM) , Root Mean Square of successive differences (RMSSD)) , Standard Deviation of RR-Intervals (SDNN) and frequency domain parameters (low frequency (LF) , high frequency (HF) and LF/HF) of HRV. Results: We examined 67 children (33 girls, 34 boys, age 25.3±1.6 months) . During pregnancy, 30 of their mothers had GDM, which was treated according to national guidelines. There were no differences between groups in birth weight, weight at age 2, and body fat. We observed statistically significant associations of GWG with heart rate, RMSSD, SDNN, HF power, and HF/LF, indicating a lower parasympathetic tone in children of mothers with low GWG. This association was attenuated in GDM-exposed children. ANS function correlated with body weight and body fat only in children from normoglycemic pregnancies (NGT) . Conclusion: We found an impact of maternal GWG on offspring ANS function, which was missing in the presence of treated GDM. The balance of the ANS was related to offspring body composition only in children from NGT pregnancies. Our results point towards a critical impact of maternal weight gain during pregnancy on the developing ANS with longstanding consequences for body composition. Disclosure L.Fritsche: None. H.Preissl: None. M.Heni: Advisory Panel; Boehringer Ingelheim International GmbH, Research Support; Boehringer Ingelheim International GmbH, Sanofi, Speaker's Bureau; Amryt Pharma Plc, Boehringer Ingelheim International GmbH, Novo Nordisk. J.Hartkopf: None. J.Hummel: None. D.Löffler: None. H.Häring: None. A.Peter: None. A.L.Birkenfeld: None. R.Wagner: Advisory Panel; Akcea Therapeutics, Daiichi Sankyo, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. A.Fritsche: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. Funding The PREG study is supported in part by a grant from the Federal Ministry of Education and Research (BMBF) (01GI0925) to the German Center for Diabetes Research (DZD) and by grant from the Deutsche Diabetes Stiftung (380/02/16) to LF

Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse.

Cystathionine beta synthase (CBS) catalyzes the first step of the transsulfuration pathway from homocysteine to cystathionine, and its deficiency leads to hyperhomocysteinemia (HHcy) in humans and rodents. To date, scarce information is available about the HHcy effect on insulin secretion, and the link between CBS activity and the setting of type 2 diabetes is still unknown. We aimed to decipher the consequences of an inborn defect in CBS on glucose homeostasis in mice. We used a mouse model heterozygous for CBS (CBS+/−) that presented a mild HHcy. Other groups were supplemented with methionine in drinking water to increase the mild to intermediate HHcy, and were submitted to a high-fat diet (HFD). We measured the food intake, body weight gain, body composition, glucose homeostasis, plasma homocysteine level, and CBS activity. We evidenced a defect in the stimulated insulin secretion in CBS+/− mice with mild and intermediate HHcy, while mice with intermediate HHcy under HFD presented an improvement in insulin sensitivity that compensated for the decreased insulin secretion and permitted them to maintain a glucose tolerance similar to the CBS+/+ mice. Islets isolated from CBS+/− mice maintained their ability to respond to the elevated glucose levels, and we showed that a lower parasympathetic tone could, at least in part, be responsible for the insulin secretion defect. Our results emphasize the important role of Hcy metabolic enzymes in insulin secretion and overall glucose homeostasis.

Evaluation of Sympathetic and Parasympathetic Tone and Reactivity in Adolescents with Specific Learning Disorder (Dyslexia).

To evaluate the autonomic function in specific learning disorder (SLD) and comorbid SLD attention-deficit hyperactivity disorder (SLD-ADHD). A cross-sectional study was conducted in a tertiary care hospital with 20 adolescent subjects each of confirmed SLD, SLD-ADHD, and healthy control (mean age 15.32 y). Heart-rate variability and autonomic-function tests were carried out using standard protocols. Heart-rate variability parameters, viz., mean RR interval, number of RR intervals which differ by ≥ 50ms (NN50), percentage NN50, standard deviation of differences between adjacent RR intervals, root square of mean of the sum of the squares of differences between adjacent RR intervals, coefficient of variance and absolute power of high-frequency band (HF) recorded apparently lower levels in SLD and SLD-ADHD as compared to healthy control indicating lower parasympathetic tone. Whereas, higher absolute power of low- frequency band (LF) in SLD and SLD-ADHD than healthy control indicated enhanced sympathetic activity. Higher LF/HF and lower SD1/SD2 ratios in SLD and SLD-ADHD than healthy control indicated higher sympathetic tone over parasympathetic tone. Values of autonomic-function tests such as E:I ratio, change in heart rate during deep-breathing test, 30:15 ratio, and Valsalva ratio showed a decrease in SLD and SLD-ADHD as compared to healthy control implying reduction in parasympathetic reactivity. Increased values for rise in diastolic blood pressure in the isometric handgrip test and cold pressor test recorded in SLD as compared to healthy control, revealed the increased sympathetic reactivity. Overall, results of heart-rate variability and autonomic-function tests imply dysregulation of sympathetic and parasympathetic activities with sympathetic dominance in SLD and SLD-ADHD.

Heart rate: control mechanisms, pathophysiology and assessment of the neurocardiac system in health and disease.

The monitoring of physiological function and dysfunction is an important principle in modern medicine. Heart rate is a basic example of this type of observation, particularly assessing the neurocardiac system, which entails the autonomic nervous system and intracardiac processes. The neurocardiac axis is an underappreciated and often overlooked system which, if measured appropriately in the clinical setting, may allow identification of patients at risk of disease progression and even mortality. While heart rate itself is a simplistic tool, more information may be gathered through assessing heart rate variability and heart rate recovery time. Studies have demonstrated an association of slow heart rate recovery and lower heart rate variability as markers of elevated sympathetic and lower parasympathetic tone. These parameters have additionally been shown to relate to development of arrhythmia, heart failure, systemic inflammatory processes, ischaemic heart disease and an increased rate of mortality. The aim of this review is to detail how heart rate is homeostatically controlled by the autonomic nervous system, how heart rate can impact on pathophysiological processes, and how heart rate variability and heart rate recovery time may be used in the clinical setting to allow the neurocardiac system to be assessed.

Re-print: Maintenance (r) Alpha Lipoic Acid Reduces Sudden Cardiac Death in Geriatric Diabetes Mellitus II Patients

Background: Diabetes carries a two-fold risk of Sudden Cardiac Death (SCD). Diabetic Autonomic Neuropathy (DAN), often progressing to Cardiovascular Autonomic Neuropathy (CAN, critically low parasympathetic tone [P]), increases death 3.5-fold over 5 years, half sudden or non- renal. Oxidative stress is a major cause of DAN. Also, increased sympathetic tone (S), High Sympathovagal Balance [SB&gt;2.5] increases SCD risk. Objective: Dysautonomic diabetic II patients were treated with the antioxidant (r) Alpha Lipoic Acid (ALA), autonomic function followed, and Sudden Death (SD) compared to untreated patients. Methods: 133 patients (mean age 66y/o) with DAN or CAN, diagnosed using the ANX 3.0 Autonomic Monitor (Physio PS, Inc., Atlanta, GA) was offered (r)-ALA: 83 agreed (Group 1), and 50 refused (Group 2). P and S were re- measured up to 3 times/yr (mean f/u 6.31 yrs); SCDs were recorded. Results: A 43% Relative Risk Reduction (RRR) in SCD occurred with (r)- ALA (25% SCD Group 1 vs. 44% SCD Group 2, p=0.0076). Initial to final patients with high SB or CAN were 21.7%-12% (p=0.010), 10.8%- 15.7% (p=0.045), Group 1 vs. 24%-22% (p=ns), 6%-12% (p=0.083), Group 2. Only Group 1 survivors increased mean resting P. The progressive increase in P’s decline, increasing CAN risk, in the other patients correlated with mortality (p&lt;0.001) and (r) ALA dose. Initially, Group 1 had insignificantly less high SB (p=0.449) and significantly more CAN (p=0.013) vs. Group 2. Finally, Group 1 had significantly less high SB (p=0.0967) vs. Group 2, also improving to insignificantly more CAN (p=0.261). Conclusion: (r)-ALA was associated with a 43% RRR of SCD and favorable P and S changes.

Maintenance (r) Alpha Lipoic Acid Reduces Sudden Cardiac Death in Geriatric Diabetes Mellitus II Patients

Background: Diabetes carries a two-fold risk of Sudden Cardiac Death (SCD). Diabetic Autonomic Neuropathy (DAN), often progressing to Cardiovascular Autonomic Neuropathy (CAN, critically low parasympathetic tone [P]), increases death 3.5-fold over 5 years, half sudden or non-renal. Oxidative stress is a major cause of DAN. Also, increased sympathetic tone (S), High Sympathovagal Balance [SB&gt;2.5] increases SCD risk. Objective: Dysautonomic diabetic II patients were treated with the antioxidant (r) Alpha Lipoic Acid (ALA), autonomic function followed, and Sudden Death (SD) compared to untreated patients. Methods: 133 patients (mean age 66y/o) with DAN or CAN, diagnosed using the ANX 3.0 Autonomic Monitor (Physio PS, Inc., Atlanta, GA) was offered (r)-ALA: 83 agreed (Group 1), and 50 refused (Group 2). P and S were re-measured up to 3 times/yr (mean f/u 6.31 yrs); SCDs were recorded. Results: A 43% Relative Risk Reduction (RRR) in SCD occurred with (r)-ALA (25% SCD Group 1 vs. 44% SCD Group 2, p=0.0076). Initial to final patients with high SB or CAN were 21.7%-12% (p=0.010), 10.8%-15.7% (p=0.045), Group 1 vs. 24%-22% (p=ns), 6%-12% (p=0.083), Group 2. Only Group 1 survivors increased mean resting P. The progressive increase in P’s decline, increasing CAN risk, in the other patients correlated with mortality (p&lt;0.001) and (r) ALA dose. Initially, Group 1 had insignificantly less high SB (p=0.449) and significantly more CAN (p=0.013) vs. Group 2. Finally, Group 1 had significantly less high SB (p=0.0967) vs. Group 2, also improving to insignificantly more CAN (p=0.261). Conclusion: (r)-ALA was associated with a 43% RRR of SCD and favorable P and S changes.

1081 Associations Among REM Density And Parasympathetic Activity, Nightmares, And Hyperarousal In Trauma-exposed Individuals

Abstract Introduction Individuals with posttraumatic stress disorder (PTSD) exhibit autonomic hyperarousal and nightmares. We hypothesized that REM density (REMD) and REM heart rate variability would predict self-reported hyperarousal, nightmares, and PTSD diagnosis in trauma-exposed individuals. Methods Ninety-nine individuals (aged 18-40, 68 females) exposed to a DSM-5 PTSD criterion-A trauma within the past two years (48 meeting PTSD criteria) completed a night of ambulatory polysomnography (PSG) preceded by an acclimation night. REMD in scored sleep recordings were computed using the Matlab program written by Benjamin Yetton. Indices of parasympathetic tone during REM were computed using Kubios software and included Average Root Mean Square of the Successive Differences (RMSSD) and High Frequency power (HFpower). Participants completed two weeks of sleep diaries with nightmare questionnaire and completed the Clinician-Administered PTSD Scale (CAPS-5) and the PTSD Checklist for DSM-5 (PCL-5). Hyperarousal-item scores were computed from the PCL-5 without the sleep item (PCLhyp) and from the CAPS-5 (CAPShyp), and these scores (with their sleep items) were combined into a Composite Hyperarousal Index (CHI). Nightmare rate was the proportion of sleep diaries reporting a nightmare. Simple regressions measured associations among REMD, REM parasympathetic indices, hyperarousal measures, and nightmare rate. Results REMD did not significantly predict PTSD diagnosis or hyperarousal scores but did predict decreased parasympathetic activity for both RMSSD (p= 0.002, R= -0.316) and HFpower (p= 0.016 R= -0.250). REMD predicted increased nightmare rate (p= 0.011 R= 0.262). Parasympathetic tone was negatively correlated with CAPShyp, PCLhyp, and CHI for both RMSSD (p= 0.04, 0.011, &amp;lt;0.000, respectively) and HFpower (p= 0.051, 0.021, 0.010, respectively). Lower parasympathetic tone also predicted PTSD diagnosis with both RMSSD (p=0.012, t=2.559) and HFpower (p=0.010, t=2.627), but did not predict nightmare rate. Conclusion REMD predicted decreased parasympathetic tone and higher nightmare rate. Parasympathetic tone, but not REMD, predicted hyperarousal and PTSD diagnosis. Support R01MH109638

Spectral Analysis of Heart Rate Variability During Mobile Phone Usage in First Year Medical Students

Background: The electromagnetic radiations emitted by cellular telephones may influence the autonomic tone which modifies the functioning of the circulatory system. Aim and Objectives: To estimate the effect of using mobile phones on heart rate variability (HRV) in first year medical students. Method: ECG and HRV parameters are recorded in three periods, - when the subject is at rest without mobile phone (Period-I), with mobile phone kept on the left chest (Period-II) and when responding to a call by keeping the mobile over his right ear (Period-III) on 100 healthy subjects aged between 18 and 21 years of either sex.Results:When the mobile was kept on chest or while attending a call,a decrease in high frequency (HF) in normalized units and increase in low frequency (LF) in normalized units and increase in the ratio of LF to HF (LF/HF) was observed in the frequency domain measures. Decrease in RR intervals, RMSSD and NN50 was observed in the time domain measures . Conclusion: The participants showed a higher sympathetic tone and a lower parasympathetic tone while attending a call. The study proved the intense effects of handset radiofrequency radiations on autonomic balance in healthy subjects.

Higher nicotinic receptor availability in the cingulo-insular network is associated with lower cardiac parasympathetic tone.

The dorsal anterior cingulate cortex (dACC) and the anterior insula (AI) constitute the salience network and form as well the major cortical components of the central autonomic nervous system. These two cortical regions have the highest density in α4β2 nicotinic acetylcholine receptors (nAChRs) within the whole cortex.The aim of the study was to test the association between nAChRs density/availability in the salience network and the heart rate variability in humans. We selected subjects from a previous positron emission tomography (PET) imaging study in epilepsy with 18F-FA-85380, a specific marker for α4β2 nAChRs, including 10 healthy controls, 10 patients with nonlesional focal epilepsy and 8 patients with idiopathic generalized epilepsy. Participants underwent a 10 min-resting electrocardiogram as they were lying still in a semi-supine position while watching an emotionally neutral video. We tested the association between parasympathetic tone and the regional brain nAChR availability, as measured by 18F-F-A-85380 binding potential (BP), using linear regression. We observed an association between higher nAChRs availability in the bilateral dACC and the right dorsal AI/frontal operculum and a lower parasympathetic tone, without significant effect of the clinical group on this relation. Our study is the first one to show a neurochemical correlate to the parasympathetic role of the anterior cingulate cortex and the AI. The nicotinic system, which plays a major role in the peripheral autonomic nervous system intervening both in the parasympathetic and sympathetic chains, seems also to play a role in the central autonomic nervous system.

Autonomic Neuromodulation for Preventing and Treating Ventricular Arrhythmias.

The cardiac autonomic nervous system (CANS) is associated with modulation of cardiac electrophysiology and arrhythmogenesis. In this mini review, we will briefly introduce cardiac autonomic anatomy and autonomic activity in ventricular arrhythmias (VAs) and discuss novel approaches of CANS modulation for treating VAs. Studies over the decades have provided a better understanding of cardiac autonomic innervation and revealed overwhelming evidence of the relationship between autonomic tone and VAs. A high sympathetic tone and low parasympathetic (vagal) tone are considered as the major triggers of VAs in patients with myocardial ischemia, which can cause sudden cardiac death. In recent years, novel methods of autonomic neuromodulation have been investigated to prevent VAs, and they have been verified as being beneficial for malignant VAs in animal models and humans. The clinical outcome of autonomic neuromodulation depends on the level of cardiac neuraxis, stimulation parameters, and patient’s pathological status. Since autonomic modulation for VA treatment is still in the early stage of clinical application, more basic and clinical studies should be performed to clarify these mechanisms and optimize autonomic neuromodulation therapies for patients with VAs in the future.

Using acoustic features of mothers’ infant-directed speech to predict changes in infant biobehavioral state

Infant directed speech is marked by exaggerated frequency modulation and strong high frequency power, features that may provide physiological cues for mobilization or calming (Porges and Lewis, 2010; Kolacz et al., 2018). We examined whether these features predicted changes in infant biobehavioral state during the Still Face Paradigm, a stressor in which the mother withdraws and reinstates social cues. 98 mother-infant dyads participated when infants were 4-8 months old. Infant heart rate and respiratory sinus arrhythmia (a measure of cardiac parasympathetic control) were derived from an electrocardiogram (ECG). Infant behavioral distress was measured by vocal, facial, and body movement distress. Mothers’ vocalizations were measured using spectral analysis within designated frequency bands and modulation using a 2-dimensional fast Fourier transform of the audio spectrogram. Maternal frequency modulation predicted decreases in infant heart rate (p = .030), mid-frequency acoustic power (500–5000 Hz) predicted increases in cardiac parasympathetic regulation in infants with low parasympathetic tone (p = .024), and high frequency power predicted increases in infant behavioral distress in infants who were not initially distressed (p = .011). These results suggest that mothers’ vocal frequency band power and modulation may be aspects of infant-directed speech that are relevant for regulating infant biobehavioral state.