Changes In Autonomic Function Research Articles

HEMODIALYSIS EFFECTS ON AUTONOMIC FUNCTION: RESULTS OF LINEAR AND NON-LINEAR ANALYSIS OF HEART-RATE-VARIABILITY AT REST AND IN RESPONSE TO PHYSICAL AND MENTAL STRESS TESTS

Objective: Cardiac arrhythmias are the most common cause of death in hemodialysis. Autonomic dysfunction plays a central role in this arrhythmogenic background. Previous studies on hemodialysis-related changes in heart-rate-variability(HRV) give contradictory results. This study investigated HRV indices both at rest and in response to physical and mental stimulation maneuvers at multiple time-points around and during the hemodialysis procedure. Design and method: Autonomic function was assessed by linear and non-linear HRV indices at pre-dialysis, during-dialysis(3 equal time-periods), post-dialysis, and on the non-dialysis day in 36 hemodialysis patients. Continuous measurement of beat-by-beat heart-rate was recorded with Finometer-PRO(The Netherlands) at rest and after orthostatic, sit-to-stand, handgrip and mental-arithmetic test. Results: The RMSSD, SD1, and SD2 indices significantly increased during dialysis(early-HD, mid-HD, late-HD periods) compared with the pre-dialysis levels(p<0.05) and returned to baseline post-dialysis(RMSSD: 54.39±83.73 vs 137.98±109.53* vs 119.85±97.34* vs 144.47±88.74* vs 85.82±121.43msec, *p<0.05 vs pre-dialysis and post-dialysis). No differences were detected in the above indices between the pre-dialysis and non-dialysis day. However, post-dialysis, the HRV responses to orthostatic and sit-to-stand tests were more exaggerated than in the pre-dialysis measurements (p<0.05). The HRV responses both at resting and physical tests in the non-dialysis day were similar to the pre-dialysis levels. HRV indices in mental-arithmetic test during hemodialysis were much higher than at the non-dialysis day(RMSSD: 77.05 (180.41) vs 19.75 (105.47)msec; p = 0.031) were detected. Conclusions: Hemodialysis causes marked changes in autonomic function. Resting HRV indices return to baseline post-dialysis, but HRV responses to physical stress remain exaggerated and return to baseline on the non-dialysis day. Detecting patients with significant autonomic dysfunction may help towards reduction of arrhythmia risk through individualized approaches.

Cardiovascular responses to static handgrip exercise and postexercise ischemia in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is characterized by reduced ability to sustain physical activity that may be due partly to disease-related changes in autonomic function that contribute to dysregulated cardiovascular control during muscular contraction. Thus, we used a combination of static handgrip exercise (HG) and postexercise ischemia (PEI) to examine the pressor response to exercise and isolate the skeletal muscle metaboreflex, respectively. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were assessed during 2-min of static HG at 30 and 40% of maximum voluntary contraction (MVC) and subsequent PEI in 16 patients with HFpEF and 17 healthy, similarly aged controls. Changes in MAP were lower in patients with HFpEF compared with controls during both 30%MVC (Δ11 ± 7 vs. Δ15 ± 8 mmHg) and 40%MVC (Δ19 ± 14 vs. Δ30 ± 8 mmHg), and a similar pattern of response was evident during PEI (30%MVC: Δ8 ± 5 vs. Δ12 ± 8 mmHg; 40%MVC: Δ13 ± 10 vs. Δ18 ± 9 mmHg) (group effect: P = 0.078 and P = 0.017 at 30% and 40% MVC, respectively). Changes in HR, CO, and TPR did not differ between groups during HG or PEI (P > 0.05). Taken together, these data suggest a reduced pressor response to static muscle contractions in patients with HFpEF compared with similarly aged controls that may be mediated partly by a blunted muscle metaboreflex. These findings support a disease-related dysregulation in neural cardiovascular control that may reduce an ability to sustain physical activity in HFpEF.NEW & NOTEWORTHY The current investigation has identified a diminution in the exercise-induced rise in arterial blood pressure (BP) that persisted during postexercise ischemia (PEI) in an intensity-dependent manner in patients with heart failure with preserved ejection fraction (HFpEF) compared with older, healthy controls. These findings suggest that the pressor response to exercise is reduced in patients with HFpEF, and this deficit may be mediated, in part, by a blunted muscle metaboreflex, highlighting the consequences of impaired neural cardiovascular control during exercise in this patient group.

Role of Meditation in Ameliorating Examination Stress Induced Changes in Cardiovascular and Autonomic Functions.

Examination stress is a very well-known model of psychological stress in students. It induces changes in systolic (SBP) and diastolic blood pressure (DBP), along with changes in heart rate variability (HRV) and baroreflex sensitivity (BRS), due to autonomic perturbations. To find out if Raj Yoga meditation (RYM) practice affects autonomic and cardiovascular function in healthy young subjects during periods of examination stress. Our primary objective was to evaluate the effect of one month of supervised RYM practice on ameliorating examination-induced changes in cardiovascular and autonomic function. The secondary objective was to measure the stress levels of medical students before and after RYM. Pre-training measurements of SBP, DBP, HRV, and BRS were done, and the Medical Student Stressor Questionnaire (MSSQ) was administered to 80 participants one month before examinations. They were then trained in RYM. Post-training assessment of the same parameters was done after examinations and also after two months. In our study, RYM training decreased DBP (p = 0.01) but not SBP. BRS showed a trend towards an increase after RYM practice, but it was not statistically significant (p = 0.44). The standard deviation of the NN interval (SDNN) (p = 0.03), low-frequency (LF) nu (0.003), and high-frequency (HF) nu (0.04) showed a statistically significant change. Average RR, median RR, average rate, square root of the mean squared differences of successive NN intervals (RMSSD), pRR, total power, LF (µs2), and LF/HF ratio were not statistically significantly different between the three groups. There was a statistically significant decline in MSSQ scores for MSSQ I (p = 0.04), MSSQ II (p = 0.04), and MSSQ IV (p = 0.03). Short-term practice of supervised RYM during stressful periods is protective for the cardiovascular and autonomic systems and decreases stress in medical students.

Effects of Covid-19 on the autonomic nervous system in elite athletes assessed by heart rate variability

IntroductionCovid-19 is a viral airway and systemic infection which can negatively affect the function of the autonomic nervous system. Cardiovascular autonomic function is essential for peak athletic performance. The aim of this study was to assess the effects of a Covid-19 disease on the autonomic nervous system of German elite athletes using heart rate variability (HRV).Methods60 elite athletes (aged 22.88 ± 4.71 years) were recruited, 30 of whom had undergone a Covid-19 disease. Heart rate (HR), blood pressure (BP) and heart rate variability (HRV) were measured during rest and during an orthostatic challenge.ResultsAt rest and after orthostatic stress blood pressure and the root mean square of successive differences (RMSDD) were significantly lower in Covid-19 athletes (COV) than in control athletes (CON) (p = 0.002 and p = 0.004, respectively); heart rate was significantly higher (p = 0.001). COV showed a significantly greater reduction in blood pressure and elevation of heart rate than CON, but the change in RMSSD did not differ significantly during the orthostatic challenge.ConclusionThese results show a change in cardiac parasympathetic activity and cardiovascular autonomic function in German elite athletes after Covid-19. These findings further the understanding of effects of the Covid-19 disease on the cardiovascular physiology in athletes. Heart rate variability may be a helpful tool in the return-to-play assessment of elite athletes.

Autonomic dysfunction is associated with the development of arterial stiffness: the Whitehall II cohort.

This study aims to examine the association between baseline level and change of autonomic nervous function with subsequent development of arterial stiffness. Autonomic nervous function was assessed in 4901 participants of the Whitehall II occupational cohort by heart rate variability (HRV) indices and resting heart rate (rHR) three times between 1997 and 2009, while arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV) measured twice between 2007 and 2013. First, individual HRV/rHR levels and annual changes were estimated. Then, we modelled the development of PWV by HRV/rHR using linear mixed effect models. First, we adjusted for sex and ethnicity (model 1), and then for socioeconomic and lifestyle factors, various clinical measurements, and medications (model 2). A decrease in HRV and unchanged rHR was associated with subsequent higher levels of PWV, but the effect of a change in HRV was less pronounced at higher ages. A typical individual aged 65years with a SDNN level of 30ms and a 2% annual decrease in SDNN had 1.32 (0.95; 1.69) higher PWV compared to one with the same age and SDNN level but with a 1% annual decrease in SDNN. Further adjustment had no major effect on the results. People who experience a steeper decline in autonomic nervous function have higher levels of arterial stiffness. The association was stronger in younger people.

Circadian regulation of glutamate release pathways shapes synaptic throughput in the brainstem nucleus of the solitary tract (NTS).

Circadian regulation of autonomic reflex pathways pairs physiological function with the daily light cycle. The brainstem nucleus of the solitary tract (NTS) is a key candidate for rhythmic control of the autonomic nervous system. Here we investigated circadian regulation of NTS neurotransmission and synaptic throughput using patch-clamp electrophysiology in brainstem slices from mice. We found that spontaneous quantal glutamate release onto NTS neurons showed strong circadian rhythmicity, with the highest rate of release during the light phase and the lowest in the dark, that were sufficient to drive day/night differences in constitutive postsynaptic action potential firing. In contrast, afferent evoked action potential throughput was enhanced during the dark and diminished in the light. Afferent-driven synchronous release pathways showed a similar decrease in release probability that did not explain the enhanced synaptic throughput during the night. However, analysis of postsynaptic membrane properties revealed diurnal changes in conductance, which, when coupled with the circadian changes in glutamate release pathways, tuned synaptic throughput between the light and dark phases. These coordinated pre-/postsynaptic changes encode nuanced control over synaptic performance and pair NTS action potential firing and vagal throughput with time of day. KEY POINTS: Vagal afferent neurons relay information from peripheral organs to the brainstem nucleus of the solitary tract (NTS) to initiate autonomic reflex pathways as well as providing important controls of food intake, digestive function and energy balance. Vagally mediated reflexes and behaviours are under strong circadian regulation. Diurnal fluctuations in presynaptic vesicle release pathways and postsynaptic membrane conductances provide nuanced control over NTS action potential firing and vagal synaptic throughput. Coordinated pre-/postsynaptic changes represent a fundamental mechanism mediating daily changes in vagal afferent signalling and autonomic function.

PHYSIOLOGICAL METRICS COLLECTED FROM WEARABLE DEVICES IDENTIFY INFLAMMATORY AND CLINICAL INFLAMMATORY BOWEL DISEASE FLARES

Inflammatory bowel disease (IBD) flares are common and unpredictable. Disease monitoring relies on symptom reporting or single timepoint assessments of stool, blood, imaging, or endoscopy—these are inconvenient and invasive and do not always reflect the patient perspective. Advances in wearable technology allow for passive, continuous and non-invasive assessment of physiological metrics including heart rate variability (HRV), the measure of small time differences between each heartbeat, a marker of autonomic nervous system function. Our group has previously demonstrated that changes in autonomic function precedes an IBD flare, can predict psychological state transitions and even identify inflammatory events including SARS-CoV-2 infection. To develop algorithms that can predict IBD flares using wearable device signatures, we launched a national wearable device study called The IBD Forecast study. To assess data quality and feasibility, the first 125 Apple Watch users to enroll were evaluated.

PHYSIOLOGICAL METRICS COLLECTED FROM WEARABLE DEVICES IDENTIFY INFLAMMATORY AND CLINICAL INFLAMMATORY BOWEL DISEASE FLARES

Abstract BACKGROUND Inflammatory bowel disease (IBD) flares are common and unpredictable. Disease monitoring relies on symptom reporting or single timepoint assessments of stool, blood, imaging, or endoscopy—these are inconvenient and invasive and do not always reflect the patient perspective. Advances in wearable technology allow for passive, continuous and non-invasive assessment of physiological metrics including heart rate variability (HRV), the measure of small time differences between each heartbeat, a marker of autonomic nervous system function. Our group has previously demonstrated that changes in autonomic function precedes an IBD flare, can predict psychological state transitions and even identify inflammatory events including SARS-CoV-2 infection. To develop algorithms that can predict IBD flares using wearable device signatures, we launched a national wearable device study called The IBD Forecast study. To assess data quality and feasibility, the first 125 Apple Watch users to enroll were evaluated. METHODS The IBD Forecast study is a prospective cohort study enrolling anyone ≥18 years of age in the United States (US) with IBD who is willing to (1) use a commercially available wearable device, (2) download our custom eHive app and (3) answer daily survey questions. HRV metrics (mean of the standard deviations of all the NN intervals [SDNN]) were analyzed using a mixed-effect cosigner model that incorporated body mass index, age, and sex. SDNN is a time domain HRV index that reflects both sympathetic and parasympathetic nervous system activity and is calculated from the variance of intervals between adjacent QRS complexes (the normal-to-normal [NN] intervals). Clinical flare was assessed with daily Patient Reported Outcome (PRO)-2 surveys (flare; PRO-2 Crohn’s disease >7, PRO-2 ulcerative colitis >2). Inflammatory flare was assessed via patient reported C-reactive protein (CRP), with inflammatory flare defined as >5 mg/L. RESULTS The first 125 study participants were enrolled across 29 states in the US (Table 1). Circadian features of changes of HRV were modelled (Figure 1). The mesor, or midline of the circadian pattern of the SDNN was higher in those with clinical flare (mean 44.43; 95% CI 41.25-47.75) compared to those in clinical remission (mean 43.03; 95% CI 39.94-46.22) (p<0.004). The mesor of the circadian pattern of the SDNN was lower in those with an inflammatory flare (mean 38.16; 95% CI 30.86-45.72) compared to those with normal inflammatory markers (mean 49.51; 95% CI 43.12-56.26) (p<0.001). CONCLUSIONS Longitudinally collected HRV metrics from a commonly worn commercial wearable device can identify symptomatic and inflammatory flares. This preliminary analysis of a small proportion of the IBD Forecast Study cohort demonstrates the feasibility of using wearable devices to identify, and may potentially predict, IBD flares.

Changes in Autonomic Nervous System Function in Patients >60 Years of Age with Coronary Heart Disease, and Normotension or Hypertension: An Observational Study

Aim: The aim of this observational study was to perform in-depth analysis of autonomic nervous system function in patients older than 60 years of age with coronary artery disease, and normotension or hypertension. Method: A total of 104 patients older than 60 years with coronary heart disease (CHD) were divided into a normotension group and hypertension (HT) group, and 24-hour Holter monitoring was performed to assess autonomic function. Result: Among the 104 patients with CHD analyzed, 52 had normotension, and 52 had hypertension. The 24-hour Holter results based on time-domain methods indicated that the values of the time-domain parameters of heart rate variability were significantly lower in the CHD+HT group than the CHD group. Furthermore, during both the daytime and nighttime, the time-domain parameters were significantly lower in the CHD+HT group than the CHD group. No difference was observed in autonomic function during the daytime and nighttime in each group. Values of frequency-domain parameters of heart rate variability were also significantly lower in the CHD+HT group than the CHD group. More patients in the CHD+HT group than the CHD group received percutaneous coronary intervention (57.69% vs. 50% χ2=0.619, P=0.55). In 12 months of follow-up, we found no significant differences in rehospitalization for unstable angina and target lesion revascularization between patients with CHD with normotension versus hypertension. Conclusion: The heart autonomic nervous system dysfunction in patients older than 60 years with CHD with hypertension was more severe than that in patients with CHD with normotension, and therefore, should receive greater clinical attention.

Effect of slow breathing exercise on heart rate variability in tension-type headache female patients: A time domain analysis

Background: Tension-type headache (TTH), the most frequently occurring primary headache is associated with autonomic dysfunction. Time domain analysis of heart rate variability (HRV) is a popular tool to detect changes in cardiac autonomic nerve function (CANF) in TTH patients. Slow breathing exercise (SBE) can significantly improve HRV in patients with cardiovascular disorders. Objective: To observe the effect of SBE on HRV by time domain analysis in TTH female patients. Methods: This quasi-experimental study was conducted from March 2021 to February 2022 in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka on 60 female TTH patients aged 20-45 years. Thirty patients performed SBE every morning and evening for 30 minutes in addition to receiving conventional treatment and 30 patients continued only conventional treatment without any exercise for 90 days. Thirty age, sex and BMI matched apparently healthy control were enrolled who did not perform SBE or any other exercise. All subjects were assessed at baseline and also after 90 days. Time domain HRV parameters were recorded by Power Lab 8/35 AD Instruments, Australia. One way ANOVA followed by post-hoc test and Paired sample t-test were performed for statistical analysis and p<0.05 was considered as statistical significance. Results: Mean heart rate (HR) was significantly higher (p<0.001) and SDRR (Standard deviation of all RR interval); CVRR (Coefficient variation of RR interval); SDSD (Standard deviation of successive RR interval differences between adjacent RR intervals); RMSSD (Square root of mean of squared differences of successive RR interval) and pRR50% (Proportion of RR interval with duration > 50ms) were significantly lower (p<0.001) in TTH female patients compared to control at baseline. Significant decrement of mean HR (p<0.001) and increment of all other time domain parameters (p<0.001) was observed after 90 days of SBE. Again, significantly decreased SDRR, CVRR, SDSD, RMSSD and pRR50% (p<0.001, p<0.01) was observed in the patients who did not perform SBE. Conclusion: SBE may effectively improve cardiac autonomic dysfunction in TTH female patients. J Bangladesh Soc Physiol. 2022, June; 17(1): 56-63

Effect of physical exercise on non-linear parameters of heart rate variability in Chronic Obstructive Pulmonary Disease

Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with autonomic nerve dysfunction. Nonlinear methods of heart rate variability (HRV) analysis have been gaining interest as a method of detecting changes in cardiac autonomic nerve function. Regular practice of physical exercise may cause improvement of this impaired autonomic nerve function. Objectives: To assess the effect of physical exercise on nonlinear measures of HRV analysis in male patients with COPD. Methods: This prospective interventional study was carried out in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka in 2018 on 60 diagnosed male COPD patients aged 40-75 years with disease duration of at least 5 years selected from the Department of Respiratory Medicine, BSMMU, Dhaka. Thirty patients underwent physical exercise (walking for 30 minute and pursed lip and diaphragmatic breathing 10 minuts)for 3 months in addition to standard treatment. Thirty (30) patients received only standard treatment for 3 months. For comparison, 30 age matched apparently healthy males were also enrolled. HRV data of all patients were recorded before and after 3 months of follow up. HRV data of healthy controls were recorded once at baseline. For assessing autonomic dysfunction, nonlinear parameters of HRV were recorded by Power Lab 8/35. For statistical analysis, paired sample t-test and independent sample t-test were done as applicable. Results: SD1, SD2 and SD1/ SD2 were found significantly lower in COPD patients compared to healthy controls at baseline. After 3 months of physical exercise, significant increment of these parameters occurred with a trend of improvement in cardiac autonomic nerve function in these patients. Conclusion: This study concluded that physical exercise can improve cardiac autonomic nerve dysfunction function in COPD patients. J Bangladesh Soc Physiol. 2022, June; 17(1): 6-13

Abstract 15665: Pod-Based Electronic Cigarette Use Alters Measures of Heart Rate Variability

Background: Previous studies demonstrate changes in autonomic function with combustible and earlier generation electronic cigarette (ecig) use. We sought to explore the effects of nicotine salt containing pod-based ecigs on autonomic regulation in young adult regular users by analyzing indices of heart rate variability (HRV). Methods: We enrolled healthy adults (18-45 yo) who were self-reported tobacco nonusers, pod-based ecig users, or combustible cigarette users. Participants were asked to refrain from tobacco product use at least 6 h before the study visit. Indices of HRV: standard deviation of the NN intervals (SDNN) and the root mean square differences of successive NN intervals (RMSSD, measure of parasympathetic function) were measured by Sphygmacor before and 10 minutes after structured use of participants’ own product. Measurements of urinary levels of cotinine, a nicotine metabolite, and 3HPMA, an acrolein metabolite, were made 1 h after product use. Results: In 133 subjects (age 26±5, 49% women), baseline HRV measures were comparable among tobacco non-users (N=39), pod-based ecig users (N=64), and combustible cigarette users (N=30). Analyses adjusted for age and sex demonstrated that acute pod-based ecig use reduced SDNN compared with non-use (-5.9±2.6ms vs 6.5±3.2ms, P=0.004) and similar to the effect of combustible cigarette use (-10.2±3.8ms, P=0.37). Moreover, acute pod-based ecig use reduced RMSSD compared with non-use (-5.6±3.3ms vs 5.4±4.1ms, P=0.04) and similar to the effect of combustible cigarette use (-10.9±4.9ms, P=0.38). Urinary cotinine, reflective of nicotine exposure, was associated with decreases in SDNN and RMSSD (r=-0.33, P=0.001; r=-0.29,P=0.003, respectively) whereas 3HPMA associated with SDNN and showed a trend toward association with RMSSD (r=-0.27, P=0.006; r=-0.18, P=0.06, respectively). Conclusion: Our data demonstrate an association between acute use of pod-based ecigs and altered cardiac autonomic function in association with the level of nicotine and acrolein exposure.

Impact of COVID-19 on cardiac autonomic function in healthy young adults: potential role of symptomatology and time since diagnosis.

Emerging evidence suggests that COVID-19 may affect cardiac autonomic function; however, the limited findings in young adults with COVID-19 have been equivocal. Notably, symptomology and time since diagnosis appear to influence vascular health following COVID-19, but this has not been explored in the context of cardiac autonomic regulation. Therefore, we hypothesized that young adults who had persistent symptoms following COVID-19 would have lower heart rate variability (HRV) and cardiac baroreflex sensitivity (BRS) compared with those who had COVID-19 but were asymptomatic at testing and controls who never had COVID-19. Furthermore, we hypothesized that there would be relationships between cardiac autonomic function measures and time since diagnosis. We studied 27 adults who had COVID-19 and were either asymptomatic (ASYM; n = 15, 6 females); 21 ± 4 yr; 8.4 ± 4.0 wk from diagnosis) or symptomatic (SYM; n = 12, 9 females); 24 ± 3 yr; 12.3 ± 6.2 wk from diagnosis) at testing, and 20 adults who reported never having COVID-19 (24 ± 4 yr, 11 females). Heart rate and beat-to-beat blood pressure were continuously recorded during 5 min of rest to assess HRV and cardiac BRS. HRV [root mean square of successive differences between normal heartbeats (RMSSD); control, 73 ± 50 ms; ASYM, 71 ± 47 ms; and SYM, 84 ± 45 ms; P = 0.774] and cardiac BRS (overall gain; control, 22.3 ± 10.1 ms/mmHg; ASYM, 22.7 ± 12.2 ms/mmHg; and SYM, 24.3 ± 10.8 ms/mmHg; P = 0.871) were not different between groups. However, we found correlations with time since diagnosis for HRV (e.g., RMSSD, r = 0.460, P = 0.016) and cardiac BRS (overall gain, r = 0.470, P = 0.014). These data suggest a transient impact of COVID-19 on cardiac autonomic function that appears mild and unrelated to persistent symptoms in young adults.NEW & NOTEWORTHY The potential role of persistent COVID-19 symptoms on cardiac autonomic function in young adults was investigated. We observed no differences in heart rate variability or cardiac baroreflex sensitivity between controls who never had COVID-19 and those who had COVID-19, regardless of symptomology. However, there were significant relationships between measures of cardiac autonomic function and time since diagnosis, suggesting that COVID-19-related changes in cardiac autonomic function are transient in young, otherwise healthy adults.

Higher pre-treatment skin sympathetic nerve activity and elevated resting heart rate after chemoradiotherapy predict worse esophageal cancer outcomes

BackgroundChemoradiotherapy (CRT), which might affect the autonomic system, is the mainstay therapy for advanced esophageal squamous cell carcinoma (ESCC). Autonomic dysfunction has been found to possibly lead to cancer mortality in those with elevated resting heart rates (RHR). Skin sympathetic nerve activity (SKNA) is a new method of stimulating electrical signals in skin to evaluate autonomic function from sympathetic tone. In this study, we investigated the association between changes in RHR and autonomic function and ESCC mortality.MethodsThirty-nine stage II-IV ESCC patients receiving CRT between March 2019 and November 2020 were prospectively enrolled and carefully selected, followed up and received the same meticulous supportive care. Serial RHR was recorded every two weeks from before CRT to eight weeks after CRT and average SKNA were recorded before and four weeks after CRT. All-cause mortality was defined as primary outcome.ResultsWe found the RHR of ESCC patients to be significantly elevated and peaking at four weeks after CRT (p < 0.001) and then to gradually decrease. Those with an elevated RHR above the cutoff level (18 beat-per-minute) at eight weeks after CRT had worse overall survival. In addition, those with higher baseline sympathetic tone (average SKNA ≥ 0.86 μV) also had poor outcome.ConclusionsIncreased pre-treatment sympathetic tone and elevated RHR after CRT are alarm signs of poor ESCC outcome. Further exploration of the mechanisms underlying these associations could potentially lead to intervention strategies for reducing mortality.Trial registrationThis study is registered with ClinicalTrials.gov, identifier: NCT03243448.

Impaired left ventricular deformation and ventricular-arterial coupling in post-COVID-19: association with autonomic dysregulation.

Coronavirus disease-19 (COVID-19) has extended implications namely the long COVID-19 syndrome. We assessed over-time changes in left ventricular (LV) function, aortic stiffness, autonomic function, and ventricular-arterial coupling (VAC) in post-COVID-19 patients. We followed 34 post-COVID-19 subjects, up to 6 months post-hospital discharge. Subjects without COVID-19 served as control. We evaluated LV global longitudinal strain (LV-GLS), arterial stiffness [carotid-femoral pulse wave velocity (cf-PWV)], and heart rate variability -standard deviation of normal RR intervals (SDNN). VAC was estimated as the ratio of cf-PWV to LV-GLS. Post-COVID-19 individuals (1-month post-hospital discharge) presented with impaired LV-GLS [−18.4%(3.1) vs. −22.0%(2.7), P < 0.001], cf-PWV [12.1 m/s (3.2) vs. 9.6 m/s (1.9), P < 0.001], SDNN [111.3 ms (22.6) vs. 147.2 ms (14.0), P < 0.001], and VAC [−0.68 (0.22) vs. −0.44 (0.10), P < 0.001] compared to control. LV-GLS, SDNN, and VAC improved at the 6-month follow-up however they did not reach control levels. In post-COVID-19 subjects, SDNN and VAC were correlated at the 1-month (R = 0.499, P = 0.003) and 6-month (R = 0.372, P = 0.04) follow-up. Long COVID-19 syndrome was associated with impaired LV-GLS, SDNN, and VAC. Post-COVID-19 subjects presented with autonomic dysregulation associated with aortic stiffness, ventricular-arterial impairment, and LV dysfunction, even 6-months post-hospital discharge. These abnormalities may be related to the presence of long COVID-19 syndrome.Graphical abstract

The Use of Orthostatic Device for 90 Minutes Does Not Change Cardiovascular and Biomechanical Parameters of Patients with Spinal Cord Injury.

Background Changes in autonomic function are often caused by spinal cord injuries, which lead to limited orthostatic positioning in these patients. Objective To investigate the cardiovascular and biomechanical parameters during 90 min of postural elevation equipment usage comparing spinal cord injury and healthy subjects. Methods A device was used that allowed patients with spinal cord injuries to remain in an orthostatic posture for 90 min. During this period, the physiological parameters were measured every 15 min. Cardiovascular parameters (heart rate, oxygen saturation, blood pressure, and autonomic nervous system) and biomechanical parameters of the plantar pressure distribution were evaluated. For blood pressure, heart rate, oxygen saturation, and autonomic nervous system, a two-way analysis of variance was applied. The mixed-effect model was applied to plantar pressure. The significance level was set at p < 0.05 for all statistical analyses. Results No differences were observed between the groups in systolic blood pressure (F = 0.07), diastolic blood pressure (F = 0.14), heart rate (F = 0.56), and oxygen saturation (F = 0.23) at any of the time intervals throughout the experiment (p > 0.05). No statistical difference was observed in the mean plantar pressure values between the groups (p = 0.35) during the period in which they remained in the orthostatic position. Conclusion The present study showed the absence of differences between spinal cord injury patients and control participants using the orthostatic device in terms of cardiovascular and biomechanical parameters over 90 min.

Autonomic changes in Huntington's disease correlate with altered central autonomic network connectivity.

Autonomic dysfunction has been described in patients with Huntington's disease, but it is unclear if these changes in autonomic tone are related to the central autonomic network. We performed a pilot study to investigate the relationship between the integrity of the central autonomic network and peripheral manifestiations of autonomic dysfunction in premanifest Huntington's disease. We recruited male participants with pre-motor-manifest Huntington's disease and a comparison group consisting of healthy, male participants of approximately the same age. As this was a pilot study, only males were included to reduce confounding. Participants underwent a resting-state functional magnetic resonance imaging study to quantify functional connectivity within the central autonomic network, as well as a resting 3-lead ECG to measure heart rate variability with a particular focus on the parasympathetic time-domain measures of root mean square of successive differences between normal heartbeats. The pre-motor-manifest Huntington's disease participants had significantly decreased root mean square of successive differences between normal heartbeats values compared with the healthy comparison group. The pre-motor-manifest Huntington's disease group had significantly lower functional connectivity within the central autonomic network, which was positively correlated with root mean square of successive differences between normal heartbeats. Patients with pre-motor-manifest Huntington's disease have reduced functional connectivity within the central autonomic network, which is significantly associated with observed changes in autonomic function.

Modulation of the autonomic nervous system by one session of spinal low-level laser therapy in patients with chronic colonic motility dysfunction.

Patients with a defecation disorder may not evoke a normal defecation reflex, or the reflex may be excessive, as a dysfunction of the spinal autonomic nervous system. Treatment with various forms of lumbar and sacral neuromodulation have shown symptom improvement, but potential changes in autonomic functioning are rarely studied. Here we evaluate the effects on autonomic function of a single session of low-level laser therapy (LLLT) on the lumbar and sacral spine in 41 patients with chronic gastrointestinal motor dysfunction. The LLLT protocol used red LED light at a wavelength of 660 nm for 10 min and infrared LED light at a wavelength of 840 nm for 10 min, followed by infrared laser light at a wavelength of 825 nm for 10 min. Effects on the autonomic nervous system were assessed by measuring heart rate variability (HRV) changes. Respiratory Sinus Arrhythmia (RSA) and Root Mean Square of Successive Differences (RMSSD) were used to quantify parasympathetic reactivity; the Baevsky’s Stress Index (SI) reflected sympathetic activity while the ratios SI/RSA and SI/RMSSD were used to show shifts in autonomic dominance. The results indicate that lumbar and sacral neuromodulation using light arrays reduced, whereas stimulation by the laser probes significantly increased parasympathetic activity. The light arrays increased whereas the laser probes significantly decreased sympathetic activity (SI). The entire protocol shifted the autonomic balance toward parasympathetic activity. The comparison of actual vs. sham neuromodulation proved that the change in HRV parameters was due to actual light stimulation and not due to the arrays and probe touching the skin. In conclusion, a single session of LLLT markedly affects autonomic nervous system activity reflected in changes in HRV which is only possible by generating activity in the spinal autonomic nerves. These results warrant a study into the effects of LLLT on restoring autonomic dysfunction in chronic refractory colonic motility disorders.

Training-related Changes In Cardiac Autonomic Function Assessed Before And After Graded Exercise Testing

Aerobic training improves cardiac autonomic function, leading to increased heart rate variability (HRV) and decreased heart rate (HR) at rest. Intense exercise such as graded exercise testing (GXT) acutely increases HR and decreases HRV, which eventually return to resting levels post-exercise. Autonomic recovery after exercise may improve with training. PURPOSE: To examine the relationship between HRV and HR before and after GXT, and to assess changes resulting from 18 weeks of aerobic training. METHODS: Healthy young adults (n = 12, 7f; age 20.9 ± 0.6) completed physiological testing prior to enrollment in a marathon training course, and again after training. Testing included a 10-minute seated monitoring of HR/HRV (REST) with a Polar RS800cx watch and chest-strap, followed by GXT, and a 20-minute seated recovery period with HR/HRV monitoring. Recovery data were divided into two 10-minute segments (REC1 and REC2) for analysis. Mean HR and the following HRV measures were assessed using Kubios HRV Version 3.3: Standard deviation (SDNN), root mean square of the successive differences (RMSSD), high frequency power (HF), low frequency power (LF), low frequency to high frequency ratio (LF/HF), sample entropy (SE), and detrended fluctuation analysis α1 (DFAα1) and α2 (DFAα2). Repeated measures ANOVA was used to compare 10-minute segments (REST, REC1, and REC2) and to assess changes with training. RESULTS: All HRV measures and HR were different between segments (p ≤ 0.05), with HR lowest during REST and highest during REC1. Similarly, HRV measures reflected greatest variability during REST and lowest during REC1. Several measures of HRV, as well as HR changed with training. Heart rate decreased (p = 0.023) at REST (75.0 ± 17.3, 70.1 ± 14.2 bpm), during REC1 (106.3 ± 13.7, 100.1 ± 10.7) and REC2 (102.8 ± 11.9, 95.6 ± 10.3). With training, RMSSD increased (REST: 56.5 ± 29.3, 64.7 ± 32.4 ms; REC1: 6.8 ± 3.4, 8.5 ± 4.5; REC2: 9.4 ± 4.5, 11.1 ± 4.1; p = 0.048). Similarly, HF (p = 0.031) and DFAα1 (p = 0.017) exhibited greater variability across the three segments after training. CONCLUSIONS: Differences in cardiac autonomic function between timepoints before and after GXT were observed. Aerobic training reduced HR and increased selected HRV variables.

Diagnosis of colonic dysmotility associated with autonomic dysfunction in patients with chronic refractory constipation

We report the first study assessing human colon manometric features and their correlations with changes in autonomic functioning in patients with refractory chronic constipation prior to consideration of surgical intervention. High-resolution colonic manometry (HRCM) with simultaneous heart rate variability (HRV) was performed in 14 patients, and the resulting features were compared to healthy subjects. Patients were categorized into three groups that had normal, weak, or no high amplitude propagating pressure waves (HAPWs) to any intervention. We found mild vagal pathway impairment presented as lower HAPW amplitude in the proximal colon in response to proximal colon balloon distention. Left colon dysmotility was observed in 71% of patients, with features of (1) less left colon HAPWs, (2) lower left colon HAPW amplitudes (69.8 vs 102.3 mmHg), (3) impaired coloanal coordination, (4) left colon hypertonicity in patients with coccyx injury. Patients showed the following autonomic dysfunction: (1) high sympathetic tone at baseline, (2) high sympathetic reactivity to active standing and meal, (3) correlation of low parasympathetic reactivity to the meal with absence of the coloanal reflex, (4) lower parasympathetic and higher sympathetic activity during occurrence of HAPWs. In conclusion, left colon dysmotility and high sympathetic tone and reactivity, more so than vagal pathway impairment, play important roles in refractory chronic constipation and suggests sacral neuromodulation as a possible treatment.