Search

We describe a protocol to examine neurophysiological (electroencephalography, EEG), cerebrovascular (ultrasound assessments of middle cerebral artery blood velocity, MCAv) and cardiorespiratory (blood pressure, oxygen saturation, end-tidal gases, respiratory rate) responses inside a hypobaric chamber. This procedure aims to standardize the methodology in experiments conducted within a hypobaric chamber such as comparing normobaric and hypobaric hypoxia. This is important because current understanding of relationships between neurophysiological activity, and cerebrovascular and cardiorespiratory responses under varying environmental conditions remains limited. This procedure combines simultaneous neurophysiological, cardiorespiratory and cerebrovascular evaluations, allowing a comprehensive understanding of electro-neurophysiological activity. Our protocol requires an hour and a half of equipment setup, 1-1.5 hours of participant set-up, and 30 minutes of experimental data collection. Since multiple simultaneous physiological recordings, including EEG in this environment, can be fraught with pitfalls, we also provide practical considerations for experimental design and recording setup. Advanced knowledge of hypobaric chamber operation is required, alongside expertise in EEG and transcranial Doppler ultrasonography. Following our procedure one will acquire simultaneous recordings of neurophysiological, cerebrovascular and cardiorespiratory data., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hutcheon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Study Design: Systematic review and meta-analysis., Objectives: Many individuals with spinal cord injury (SCI) experience autonomic dysfunction, including profound impairments to bowel and cardiovascular function. Neurogenic bowel dysfunction (NBD) is emerging as a potential determinant of quality of life (QoL) after SCI. For individuals with high-level lesions ( > T6), bowel care-related autonomic dysreflexia (B-AD; profound episodic hypertension) further complicates bowel care. We aimed to evaluate the extent of bowel dysfunction after SCI, and the impact of bowel dysfunction on QoL after SCI., Methods: We searched five databases to identify research assessing the influence of NBD or B-AD on QoL after SCI. Metrics of bowel dysfunction (fecal incontinence [FI], constipation, time to complete, and B-AD) and QoL data were extracted and synthesised. Where possible, meta-analyses were performed., Results: Our search identified 2042 titles, of which 39 met our inclusion criteria. Individuals with SCI identified problems with NBD (74.7%), FI (56.9%), and constipation (54.6%), and 49.3% of individuals with SCI > T6 experienced B-AD. Additionally, 40.3% of individuals experienced prolonged defecation ( > 30 min). Moderate/severe deterioration in QoL due to NBD was reported by 55.5% of individuals with SCI, with negative impacts on physical, emotional, and social health-related QoL associated with inflexibility of bowel routines, fear of accidents, and loss of independence., Conclusion: Bowel dysfunction and bowel care challenges are prevalent and disabling for individuals with SCI, with a profoundly negative impact on QoL. Improving bowel management is a key target to improve QoL for those living with SCI., (© 2024. The Author(s).)

Aims: Detraining refers to a loss of training adaptations resulting from reductions in training stimulus due to illness, injury, or active recovery breaks in a training cycle and is associated with a reduction in left ventricular mass (LVM). The purpose of this study was to conduct a systematic review and meta-analysis to determine the influence of detraining on LVM in endurance-trained, healthy individuals., Methods and Results: Using electronic databases (e.g. EMBASE and MEDLINE), a literature search was performed looking for prospective detraining studies in humans. Inclusion criteria were adults, endurance-trained individuals with no known chronic disease, detraining intervention >1 week, and pre- and post-detraining LVM reported. A pooled statistic for random effects was used to assess changes in LVM with detraining. Fifteen investigations (19 analyses) with a total of 196 participants (ages 18-55 years, 15% female) met inclusion criteria, with detraining ranging between 1.4 and 15 weeks. The meta-analysis revealed a significant reduction in LVM with detraining (standardized mean difference = -0.586; 95% confidence interval = -0.817, -0.355; P < 0.001). Independently, length of detraining was not correlated with the change in LVM. However, a meta-regression model revealed length of the detraining, when training status was accounted for, was associated with the reduction of LVM (Q = 15.20, df = 3, P = 0.0017). Highly trained/elite athletes had greater reductions in LVM compared with recreational and newly trained individuals (P < 0.01). Limitations included relatively few female participants and inconsistent reporting of intervention details., Conclusion: In summary, LVM is reduced following detraining of one week or more. Further research may provide a greater understanding of the effects of sex, age, and type of detraining on changes in LVM in endurance-trained individuals., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Vasovagal syncope (VVS), or fainting, is frequently triggered by pain, fear, or emotional distress, especially with blood-injection-injury stimuli. We aimed to examine the impact of intravenous (IV) instrumentation on orthostatic tolerance (OT; fainting susceptibility) in healthy young adults. We hypothesized that pain associated with IV procedures would reduce OT., Methods: In this randomised, double-blind, placebo-controlled, cross-over study, participants (N = 23; 14 women; age 24.2 ± 4.4 years) underwent head-up tilt with combined lower body negative pressure to presyncope on three separate days: (1) IV cannulation with local anaesthetic cream (EMLA) (IV + EMLA); (2) IV cannulation with placebo cream (IV + Placebo); (3) sham IV cannulation with local anaesthetic cream (Sham + EMLA). Participants rated pain associated with IV procedures on a 1-5 scale. Cardiovascular (finger plethysmography and electrocardiogram; Finometer Pro), and forearm vascular resistance (FVR; brachial Doppler) responses were recorded continuously and non-invasively., Results: Compared to Sham + EMLA (27.8 ± 2.4 min), OT was reduced in IV + Placebo (23.0 ± 2.8 min; p = 0.026), but not in IV + EMLA (26.2 ± 2.2 min; p = 0.185). Pain was increased in IV + Placebo (2.8 ± 0.2) compared to IV + EMLA (2.0 ± 2.2; p = 0.002) and Sham + EMLA (1.1 ± 0.1; p < 0.001). Orthostatic heart rate responses were lower in IV + Placebo (84.4 ± 3.1 bpm) than IV + EMLA (87.3 ± 3.1 bpm; p = 0.007) and Sham + EMLA (87.7 ± 3.1 bpm; p = 0.001). Maximal FVR responses were reduced in IV + Placebo (+ 140.7 ± 19.0%) compared to IV + EMLA (+ 221.2 ± 25.9%; p < 0.001) and Sham + EMLA (+ 190.6 ± 17.0%; p = 0.017)., Conclusions: Pain plays a key role in predisposing to VVS following venipuncture, and our data suggest this effect is mediated through reduced capacity to achieve maximal sympathetic activation during orthostatic stress. Topical anaesthetics, such as EMLA, may reduce the frequency and severity of VVS during procedures requiring needles and intravascular instrumentation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Advanced blood pressure monitoring devices contain algorithms that permit estimation of stroke volume (SV). Modelflow (Finapres Medical Systems) is one common method to non-invasively estimate beat-to-beat SV. However, Modelflow accuracy during profound reductions in SV is unclear. We aimed to compare SV estimation by Modelflow and echocardiography, at rest and during orthostatic challenge. We tested 13 individuals (age 24 ± 2 years; 7 female) using combined head-up tilt and graded lower body negative pressure, continued until presyncope. SV was derived by both Modelflow and echocardiography on multiple occasions while supine, during orthostatic stress, and at presyncope. SV index (SVI) was determined by normalising SV for body surface area. Bias and limits of agreement were determined using Bland-Altman analyses. Two one-sided tests (TOST) examined equivalency. Across all timepoints, Modelflow estimates of SV (73.2 ± 1.6 ml) were strongly correlated with echocardiography estimates (66.1 ± 1.3 ml) (r = 0.56, P  < 0.001) with a bias of +7.1 ± 21.1 ml. Bias across all timepoints was further improved when SV was indexed (+3.6 ± 12.0 ml.m -2 ). Likewise, when assessing responses relative to baseline, Modelflow estimates of SV (-23.4 ± 1.4%) were strongly correlated with echocardiography estimates (-19.2 ± 1.3%) (r = 0.76, P  < 0.001), with minimal bias (-4.2 ± 13.1%). TOST testing revealed equivalency to within 15% of the clinical standard for SV and SVI, both expressed as absolute values and relative to baseline. Modelflow can be used to track changes in SV during profound orthostatic stress, with accuracy enhanced with correction relative to baseline values or body size. These data support the use of Modelflow estimates of SV for autonomic function testing., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Normobaric hypoxia (NH) and hypobaric hypoxia (HH) are both used to train aircraft pilots to recognize symptoms of hypoxia. NH (low oxygen concentration) training is often preferred because it is more cost effective, simpler, and safer than HH. It is unclear, however, whether NH is neurophysiologically equivalent to HH (high altitude). Previous studies have shown that neural oscillations, particularly those in the alpha band (8-12 Hz), are impacted by hypoxia. Attention tasks have been shown to reliably modulate alpha oscillations, although the neurophysiological impacts of hypoxia during cognitive processing remains poorly understood. To address this we investigated induced and evoked power alongside physiological data while participants performed an attention task during control (normobaric normoxia or NN), NH (fraction of inspired oxygen = 12.8%, partial pressure of inspired oxygen = 87.2 mmHg), and HH (3962 m, partial pressure of inspired oxygen = 87.2 mmHg) conditions inside a hypobaric chamber. No significant differences between NH and HH were found in oxygen saturation, end tidal gases, breathing rate, middle cerebral artery velocity and blood pressure. Induced alpha power was significantly decreased in NH and HH when compared to NN. Participants in the HH condition showed significantly increased induced lower-beta power and evoked higher-beta power, compared with the NH and NN conditions, indicating that NH and HH differ in their impact on neurophysiological activity supporting cognition. NH and HH were found not to be neurophysiologically equivalent as electroencephalography was able to differentiate NH from HH., (© 2023. Springer Nature Limited.)

Study Design: Multicentre, cross-sectional study., Objectives: To determine if clinical measures of poor mental health (MH-) and neuropathic pain (NP) are related to increased CVD risk in individuals with chronic spinal cord injury (SCI), and further elucidate the relationships between CVD risk, autonomic function, NP, and MH-., Setting: Eight SCI rehabilitation centres in the Netherlands., Methods: Individuals (n = 257) with a traumatic, chronic (≥10 yrs) SCI, with age at injury between 18-35 years, completed a self-report questionnaire and a one-day visit to a rehabilitation centre for testing. CVD risk was calculated using Framingham risk score. NP was inferred using The Douleur Neuropathique 4 clinical examination, and MH- was assessed using the five-item Mental Health Inventory questionnaire. Cardiovascular autonomic function was determined from peak heart rate during maximal exercise (HR peak )., Results: There was a high prevalence of both NP (39%) and MH- (45%) following SCI. MH- was significantly correlated with an adverse CVD risk profile (r = 0.174; p = 0.01), increased the odds of adverse 30-year CVD risk by 2.2 (CI 0.92-2.81, p = 0.02), and is an important variable in determining CVD risk (importance=0.74, p = 0.05). Females (p = 0.05) and those with a higher HR peak (p = 0.046) tended to be more likely to have NP., Conclusions: Clinical measures of MH-, but not NP, are important factors for increased CVD risk following SCI. NP tended to be more prevalent in those with more preserved cardiovascular autonomic function. The interrelationships between secondary consequences of SCI are complex and need further exploration., (© 2023. The Author(s), under exclusive licence to International Spinal Cord Society.)

High-altitude indoctrination (HAI) trains individuals to recognize symptoms of hypoxia by simulating high-altitude conditions using normobaric (NH) or hypobaric (HH) hypoxia. Previous studies suggest that despite equivalent inspired oxygen levels, physiological differences could exist between these conditions. In particular, differences in neurophysiological responses to these conditions are not clear. Our study aimed to investigate correlations between oxygen saturation (SpO 2 ) and neural responses in NH and HH. We recorded 5-min of resting-state eyes-open electroencephalogram (EEG) and SpO 2 during control, NH, and HH conditions from 13 participants. We applied a multivariate framework to characterize correlations between SpO 2 and EEG measures (spectral power and multiscale entropy [MSE]), within each participant and at the group level. Participants were desaturating during the first 150 s of NH versus steadily desaturated in HH. We considered the entire time interval, first and second half intervals, separately. All the conditions were characterized by statistically significant participant-specific patterns of EEG-SpO 2 correlations. However, at the group level, the desaturation period expressed a robust pattern of these correlations across frequencies and brain locations. Specifically, the first 150 s of NH during desaturation differed significantly from the other conditions with negative absolute alpha power-SpO 2 correlations and positive MSE-SpO 2 correlations. Once steadily desaturated, NH and HH had no significant differences in EEG-SpO 2 correlations. Our findings indicate that the desaturating phase of hypoxia is a critical period in HAI courses, which would require developing strategies for mitigating the hypoxic stimulus in a real-world situation., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Introduction: Healthy individuals with poor cardiovascular control, but who do not experience syncope (fainting), adopt an innate strategy of increased leg movement in the form of postural sway that is thought to counter orthostatic (gravitational) stress on the cardiovascular system. However, the direct effect of sway on cardiovascular hemodynamics and cerebral perfusion is unknown. If sway produces meaningful cardiovascular responses, it could be exploited clinically to prevent an imminent faint., Methods: Twenty healthy adults were instrumented with cardiovascular (finger plethysmography, echocardiography, electrocardiogram) and cerebrovascular (transcranial Doppler) monitoring. Following supine rest, participants performed a baseline stand (BL) on a force platform, followed by three trials of exaggerated sway (anterior-posterior, AP; mediolateral, ML; square, SQ) in a randomized order., Results: All exaggerated postural sway conditions improved systolic arterial pressure (SAP, p = 0.001) responses, while blunting orthostatic reductions in stroke volume (SV, p < 0.01) and cerebral blood flow (CBFv, p < 0.05) compared to BL. Markers of sympathetic activation (power of low-frequency oscillations in SAP, p < 0.001) and maximum transvalvular flow velocity ( p < 0.001) were reduced during exaggerated sway conditions. Responses were dose-dependent, with improvements in SAP ( p < 0.001), SV ( p < 0.001) and CBFv ( p = 0.009) all positively correlated with total sway path length. Coherence between postural movements and SAP ( p < 0.001), SV ( p < 0.001) and CBFv ( p = 0.003) also improved during exaggerated sway., Discussion: Exaggerated sway improves cardiovascular and cerebrovascular control and may supplement cardiovascular reflex responses to orthostatic stress. This movement provides a simple means to boost orthostatic cardiovascular control for individuals with syncope, or those with occupations that require prolonged motionless standing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Williams, Hockin, Heeney, Elabd, Chong, Blaber, Robinovitch, Parsons and Claydon.)

Physical counter pressure maneuvers (CPM) are movements that are recommended to delay or prevent syncope (fainting) by recruiting the skeletal muscle pump to augment cardiovascular control. However, these recommendations are largely based on theoretical benefit, with limited data evaluating the efficacy of CPM to prevent syncope in the real-world setting. We conducted a semi-systematic literature review and meta-analysis to assess CPM efficacy, identify literature gaps, and highlight future research needs. Articles were identified through a literature search (PubMed, April 2022) of peer-reviewed publications evaluating the use of counter pressure or other lower body maneuvers to prevent syncope. Two team members independently screened records for inclusion and extracted data. From 476 unique records identified by the search, 45 met inclusion criteria. Articles considered various syncopal conditions (vasovagal = 12, orthostatic hypotension = 8, postural orthostatic tachycardia syndrome = 1, familial dysautonomia = 2, spinal cord injury = 1, blood donation = 10, healthy controls = 11). Maneuvers assessed included hand gripping, leg fidgeting, stepping, tiptoeing, marching, calf raises, postural sway, tensing (upper, lower, whole body), leg crossing, squatting, "crash" position, and bending foreword. CPM were assessed in laboratory-based studies ( N = 28), the community setting ( N = 4), both laboratory and community settings ( N = 3), and during blood donation ( N = 10). CPM improved standing systolic blood pressure (+ 14.8 ± 0.6 mmHg, p < 0.001) and heart rate (+ 1.4 ± 0.5 bpm, p = 0.006), however, responses of total peripheral resistance, stroke volume, or cerebral blood flow were not widely documented. Most patients experienced symptom improvement following CPM use (laboratory: 60 ± 4%, community: 72 ± 9%). The most prominent barrier to employing CPM in daily living was the inability to recognize an impending faint. Patterns of postural sway may also recruit the skeletal muscle pump to enhance cardiovascular control, and its potential as a discrete, proactive CPM needs further evaluation. Physical CPM were successful in improving syncopal symptoms and producing cardiovascular responses that may bolster against syncope; however, practical limitations may restrict applicability for use in daily living., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Williams, Khan and Claydon.)

Autonomic dysfunction is a prominent concern following spinal cord injury (SCI). In particular, autonomic dysreflexia (AD; paroxysmal hypertension and concurrent bradycardia in response to sensory stimuli below the level of injury) is common in autonomically-complete injuries at or above T6. AD is currently defined as a >20 mmHg increase in systolic arterial pressure (SAP) from baseline, without heart rate (HR) criteria. Urodynamics testing (UDS) is performed routinely after SCI to monitor urological sequelae, often provoking AD. We, therefore, aimed to assess the cardiovascular and cerebrovascular responses to UDS and their association with autonomic injury in individuals with chronic (>1 year) SCI. Following blood draw (plasma norepinephrine [NE]), continuous SAP, HR, and middle cerebral artery blood flow velocity (MCAv) were recorded at baseline (10-minute supine), during standard clinical UDS, and recovery (10-minute supine) ( n = 22, age 41.1 ± 2 years, 15 male). Low frequency variability in systolic arterial pressure (LF SAP; a marker of sympathetic modulation of blood pressure) and cerebral resistance were determined. High-level injury (≥T6) with blunted/absent LF SAP (<1.0 mmHg 2 ) and/or low plasma NE (<0.56 nmol•L -1 ) indicated autonomically-complete injury. Known electrocardiographic markers of atrial (p-wave duration variability) and ventricular arrhythmia (T-peak-T-end variability) were evaluated at baseline and during UDS. Nine participants were determined as autonomically-complete, yet 20 participants had increased SAP >20 mmHg during UDS. Qualitative autonomic assessment did not discriminate autonomic injury. Maximum SAP was higher in autonomically-complete injuries (207.1 ± 2.3 mmHg) than autonomically-incomplete injuries (165.9 ± 5.3 mmHg) during UDS ( p < 0.001). HR during UDS was reduced compared to baseline ( p = 0.056) and recovery ( p = 0.048) only in autonomically-complete lesions. MCAv was not different between groups or phases (all p > 0.05). Cerebrovascular resistance index was increased during UDS in autonomically-complete injuries compared to baseline ( p < 0.001) and recovery ( p < 0.001) reflecting intact cerebral autoregulation. Risk for both atrial and ventricular arrhythmia increased during UDS compared to baseline ( p < 0.05), particularly in autonomically-complete injuries ( p < 0.05). UDS is recommended yearly in chronic SCI but is associated with profound AD and an increased risk of arrhythmia, highlighting the need for continued monitoring during UDS. Our data also highlight the need for HR criteria in the definition of AD and the need for quantitative consideration of autonomic function after SCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sahota, Lucci, McGrath, Ravensbergen and Claydon.)

Orthostatic hypotension is an unusually large decrease in blood pressure on standing that increases the risk of adverse outcomes even when asymptomatic. Improvements in haemodynamic profiling with continuous blood pressure measurements have uncovered four major subtypes: initial orthostatic hypotension, delayed blood pressure recovery, classic orthostatic hypotension, and delayed orthostatic hypotension. Clinical presentations are varied and range from cognitive slowing with hypotensive unawareness or unexplained falls to classic presyncope and syncope. Establishing whether symptoms are due to orthostatic hypotension requires careful history taking, a thorough physical examination, and supine and upright blood pressure measurements. Management and prognosis vary according to the underlying cause, with the main distinction being whether orthostatic hypotension is neurogenic or non-neurogenic. Neurogenic orthostatic hypotension might be the earliest clinical manifestation of Parkinson's disease or related synucleinopathies, and often coincides with supine hypertension. The emerging variety of clinical presentations advocates a stepwise, individualised, and primarily non-pharmacological approach to the management of orthostatic hypotension. Such an approach could include the cessation of blood pressure lowering drugs, adoption of lifestyle measures (eg, counterpressure manoeuvres), and treatment with pharmacological agents in selected cases., Competing Interests: Declaration of interests HK is supported by grants from the Familial Dysautonomia Foundation, the Michael J Fox Foundation for Parkinson's Research, the Multiple System Atrophy Coalition, the National Institutes of Health (NIH; R01HL103988 and U54NS065736), and the US Food and Drug Administration (FDR3731–01); receives royalties from Up to Date; receives consultancy and speakers’ fees from Med-IQ, Biogen, Biohaven Pharmaceuticals, Lundbeck, Pfizer, and Theravance Biopharma; and serves as the editor-in-chief of Clinical Autonomic Research. VEC is supported by grants from the Canadian Institutes of Health Research, the National Sciences and Engineering Research Council of Canada, the International Collaboration on Repair Discoveries, the Heart and Stroke Foundation of Canada, and the Craig H Neilsen Foundation. SPJ is supported by NIH grants K23HL135273 and R56HL153191. RDT reports consultancy and speakers’ fees from Union Chimique Belge, GlaxoSmithKline, Theravance, Novartis, and Zogenix; and grants from the Dutch National Epilepsy Fund, the Michael J Fox Foundation for Parkinson's Research (MJFF-020200), Christelijke Vereniging voor de Verpleging van Lijders aan Epilepsie, Medtronic, New Life Wearables, and The Netherlands Organisation for Health Research and Development (114025101). All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Improvement to autonomic processes such as bladder, bowel and sexual function are prioritised by individuals with spinal cord injury (SCI). Bowel care is associated with high levels of dissatisfaction and decreased quality of life. Despite dissatisfaction, 71% of individuals have not changed their bowel care routine for at least 5 years, highlighting a disconnect between dissatisfaction with bowel care and changing routines to optimise bowel care., Objective: Using an integrated knowledge translation approach, we aimed to explore the barriers and facilitators to making changes to bowel care in individuals with SCI., Methods: Our approach was guided by the Behaviour Change Wheel and used the Theoretical Domains Framework (TDF). Semi-structured interviews were conducted with individuals with SCI (n = 13, mean age 48.6 ± 13.1 years) and transcribed verbatim (duration 31.9 ± 7.1 min). Barriers and facilitators were extracted, deductively coded using TDF domains and inductively analysed for themes within domains., Results: Changing bowel care after SCI was heavily influenced by four TDF domains: environmental context and resources (workplace flexibility, opportunity or circumstance, and access to resources); beliefs about consequences; social influences (perceived support and peer mentorship); and knowledge (knowledge of physiological processes and bowel care options). All intervention functions and policy categories were considered viable intervention options, with human (61%) and digital (33%) platforms preferred., Conclusions: Modifying bowel care is a multi-factorial behaviour. These findings will support the systematic development and implementation of future interventions to both enable individuals with SCI to change their bowel care and to facilitate the optimisation of bowel care approaches., (© 2022. The Author(s).)

Background: Orthostatic syncope (transient loss of conscious when standing-fainting) is common and negatively impacts quality of life. Many patients with syncope report experiencing fatigue, sometimes with "brain fog", which may further impact their quality of life, but the incidence and severity of fatigue in patients with syncope remain unclear. In this systematic review, we report evidence on the associations between fatigue and conditions of orthostatic syncope., Methods: We performed a comprehensive literature search of four academic databases to identify articles that evaluated the association between orthostatic syncope [postural orthostatic tachycardia syndrome (POTS), vasovagal syncope (VVS), orthostatic hypotension (OH)] and fatigue. Studies were independently screened using a multi-stage approach by two researchers to maintain consistency and limit bias., Results: Our initial search identified 2797 articles, of which 13 met our inclusion criteria (POTS n = 10; VVS n = 1; OH n = 1; VVS and POTS n = 1). Fatigue scores were significantly higher in patients with orthostatic syncope than healthy controls, and were particularly severe in those with POTS. Fatigue associated with orthostatic syncope disorders spanned multiple domains, with each dimension contributing equally to increased fatigue. "Brain fog" was an important symptom of POTS, negatively affecting productivity and cognition. Finally, fatigue was negatively associated with mental health in patients with POTS., Conclusion: In conditions of orthostatic syncope, fatigue is prevalent and debilitating, especially in patients with POTS. The consideration of fatigue in patients with orthostatic disorders is essential to improve diagnosis and management of symptoms, thus improving quality of life for affected individuals., (© 2022. The Author(s).)

Purpose: Bolus water drinking, at room temperature, has been shown to improve orthostatic tolerance (OT), probably via sympathetic activation; however, it is not clear whether the temperature of the water bolus modifies the effect on OT or the cardiovascular responses to orthostatic stress. The aim of this study was to assess whether differing water temperature of the water bolus would alter time to presyncope and/or cardiovascular parameters during incremental orthostatic stress., Methods: Fourteen participants underwent three head-up tilt (HUT) tests with graded lower body negative pressure (LBNP) continued until presyncope. Fifteen minutes prior to each HUT, participants drank a 500 mL bolus of water which was randomised, in single-blind crossover fashion, to either room temperature water (20 °C) (ROOM), ice-cold water (0-3 °C) (COLD) or warm water (45 °C) (WARM). Cardiovascular parameters were monitored continuously., Results: There was no significant difference in OT in the COLD (33 ± 3 min; p = 0.3321) and WARM (32 ± 3 min; p = 0.6764) conditions in comparison to the ROOM condition (31 ± 3 min). During the HUT tests, heart rate and cardiac output were significantly reduced (p < 0.0073), with significantly increased systolic blood pressure, stroke volume, cerebral blood flow velocity and total peripheral resistance (p < 0.0054), in the COLD compared to ROOM conditions., Conclusions: In healthy controls, bolus cold water drinking results in favourable orthostatic cardiovascular responses during HUT/LBNP without significantly altering OT. Using a cold water bolus may result in additional benefits in patients with orthostatic intolerance above those conferred by bolus water at room temperature (by ameliorating orthostatic tachycardia and enhancing vascular resistance responses). Further research in patients with orthostatic intolerance is warranted., (© 2022. Crown.)

Salt supplementation is a common non-pharmacological approach to the management of recurrent orthostatic syncope or presyncope, particularly for patients with vasovagal syncope (VVS) or postural orthostatic tachycardia syndrome (POTS), although there is limited consensus on the optimal dosage, formulation and duration of treatment. Accordingly, we reviewed the evidence for the use of salt supplementation to reduce susceptibility to syncope or presyncope in patients with VVS and POTS. We found that short-term (~3 months) salt supplementation improves susceptibility to VVS and associated symptoms, with little effect on supine blood pressure. In patients with VVS, salt supplementation is associated with increases in plasma volume, and an increase in the time taken to provoke a syncopal event during orthostatic tolerance testing, with smaller orthostatic heart rate increases, enhanced peripheral vascular responses to orthostatic stress, and improved cerebral autoregulation. Responses were most pronounced in those with a baseline sodium excretion <170 mmol/day. Salt supplementation also improved symptoms, plasma volume, and orthostatic responses in patients with POTS. Salt supplementation should be considered for individuals with recurrent and troublesome episodes of VVS or POTS without cardiovascular comorbidities, particularly if their typical urinary sodium excretion is low, and their supine blood pressure is not elevated. The efficacy of the response, in terms of the improvement in subjective and objective markers of orthostatic intolerance, and any potential deleterious effect on supine blood pressure, should be routinely monitored in individuals on high salt regimes., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Abnormalities in orthostatic blood pressure changes upon active standing are associated with morbidity, mortality, and reduced quality of life. However, over the last decade, several population-based cohort studies have reported a remarkably high prevalence (between 25 and 70%) of initial orthostatic hypotension (IOH) among elderly individuals. This has raised the question as to whether the orthostatic blood pressure patterns in these community-dwelling elderly should truly be considered as pathological. If not, redefining of the systolic cutoff values for IOH (i.e., a value ≥ 40 mmHg in systolic blood pressure in the first 15 s after standing up) might be necessary to differ between normal aging and true pathology. Therefore, in this narrative review, we provide a critical analysis of the current reference values for the changes in systolic BP in the first 60 s after standing up and discuss how these values should be applied to large population studies. We will address factors that influence the magnitude of the systolic blood pressure changes following active standing and the importance of standardization of the stand-up test, which is a prerequisite for quantitative, between-subject comparisons of the postural hemodynamic response., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Effective end-organ peripheral vascular resistance responses are critical to blood pressure control while upright, and prevention of syncope (fainting). The Valsalva maneuver (VM) induces blood pressure decreases that evoke baroreflex-mediated vasoconstriction. We characterized beat-to-beat forearm vascular resistance (FVR) responses to the VM in healthy adults, evaluated the impact of age and sex on these responses, and investigated their association with orthostatic tolerance (OT; susceptibility to syncope). We hypothesized that individuals with smaller FVR responses would be more susceptible to syncope., Methods: Healthy young (N = 36; 19 women; age 25.4 ± 4.6 years) and older (N = 21; 12 women; age 62.4 ± 9.6 years) adults performed a supine 40 mmHg, 20 s VM. Graded 60° head-up-tilt with combined lower body negative pressure continued to presyncope was used to determine OT. Non-invasive beat-to-beat blood pressure and heart rate (finger plethysmography) were recorded continuously. FVR was calculated as mean arterial pressure (MAP) divided by brachial blood flow velocity (Doppler ultrasound) relative to baseline., Results: The VM produces a distinctive FVR pattern that peaks (+137.1 ± 11.6%) in phase 2B (17.5 ± 0.3 s) as the baroreflex responds to low-pressure perturbations. This response increased with age overall (p < 0.001) and within male (p = 0.030) and female subgroups (p < 0.001). Maximum FVR during the VM was significantly correlated with maximal tilt FVR (r = 0.364; p = 0.0153) and with OT when expressed relative to the MAP decrease in phase 2A (Max FVR (%)/MAP 2A-1 ; r = 0.337; p = 0.0206)., Conclusion: This is the first characterization of FVR responses to the VM. The VM elicits large baroreflex-mediated increases in FVR; small FVR responses to the VM may indicate susceptibility to syncope., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Effective baroreflex-mediated cardiac and vascular resistance responses are crucial for homeostatic blood pressure control. We investigated the impacts of age and sex on arterial blood pressure regulation during a standard supine Valsalva maneuver (40 mmHg, 20s) in 46 healthy young and 25 healthy older adults. Noninvasive, continuous cardiovascular parameters were recorded. In older adults, cardiac output (older: -58.4 ± 2.4%; young: -40.8 ± 1.4%; p < 0.001) and stroke volume (older: -63.6 ± 2.6%; young: -48.7 ± 1.9%; p < 0.001) fell more than in young adults and was compensated by augmented vascular resistance responses (older: +189.8 ± 17.6%; young: +105.8 ± 6.7; p < 0.001); heart rate responses were attenuated in older adults. Male and female responses were comparable in their respective age groups., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Injury to descending autonomic (sympathetic) pathways is common after high-level spinal cord injury (SCI) and associated with abnormal blood pressure and heart rate regulation. In individuals with high-level SCI, abnormal sympathovagal balance (such as during autonomic dysreflexia; paroxysmal hypertension provoked by sensory stimuli below the injury) is proarrhythmogenic. Exercise training is a key component of SCI rehabilitation and management of cardiovascular disease risk, but it is unclear whether exercise training influences susceptibility to cardiac arrhythmia. We aimed to evaluate: (i) whether susceptibility to arrhythmia increases in a rodent-model of SCI; (ii) the impact of the sympathomimetic drug dobutamine (DOB) on arrhythmia risk; (iii) whether exercise training ameliorates arrhythmia risk. Twenty-one Wistar rats were divided into 3 subgroups: T2-contusive SCI (T2, n = 7), T2-contusive SCI completing passive hindlimb cycling training (PHLC, n = 7), and T10-contusive SCI (T10, n = 7). Known electrocardiographic arrhythmia markers and heart rate variability parameters were evaluated before (PRE), 1-week (POST) and 5-weeks post-SCI (TERM) at baseline and during DOB infusion (30 μg/kg/min). Baseline markers of arrhythmia risk were increased in both T2 and T10 animals. DOB decreased R-R interval (p < 0.001), and increased markers of risk for ventricular arrhythmia, particularly in high-level (T2) animals (p < 0.05). Exercise training blunted the exacerbation of markers of arrhythmia risk in the presence of DOB. Markers of risk for cardiac arrhythmia are increased in experimental SCI, and DOB further increases arrhythmia risk in high-level SCI. Exercise training did not improve markers of arrhythmia risk at rest, but did ameliorate markers of arrhythmia risk during sympathetic stimulation., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Study Design: Multicentre, cross-sectional study., Objectives: To identify which markers of obesity, injury characteristics and autonomic function variables are related to cardiovascular disease (CVD) risk after spinal cord injury (SCI), and establish cut-points for detection and risk management., Setting: Eight SCI rehabilitation centres in the Netherlands., Methods: Individuals (n = 257) with a traumatic, chronic (≥10 years) SCI, with age at injury between 18 and 35 years, completed a self-report questionnaire and a one-day visit to a rehabilitation centre for testing. Three anthropometric measures were tested: body mass index (BMI); waist circumference (WC); and waist-to-height ratio (WHtR). Injury characteristics included: American Spinal Injury Association impairment scale (AIS); duration of injury (DOI); and neurological level of injury (LOI). Cardiovascular autonomic function was assessed from peak heart rate during maximal exercise (HR peak ). Systolic arterial pressure (SAP) and aerobic capacity (VO 2peak ) were also determined. CVD risk was calculated using the Framingham risk score (FRS)., Results: All anthropometric variables were associated with FRS, with WC showing the strongest correlation (r = 0.41, p < 0.001) and greatest area under the curve (0.73) for 10-year CVD risk (%). WC, DOI, SAP, HR peak , LOI, and VO 2peak (variable importance: 0.81, 1.0, 0.98, 0.98, 0.66, 0.68, respectively) were important predictive variables for 10-year CVD risk in individuals with SCI., Conclusions: We confirm that WC is a simple, practical measure of CVD risk, and along with DOI and markers of cardiovascular autonomic function, plays a role in the increased CVD risk following SCI.

Sodium intake and compliance with dietary sodium modification are typically assessed using a 24-h urine collection analyzed using flame photometry, but this is inconvenient. Spot urine samples have been investigated as alternatives to 24-h collections, but their accuracy is poor. Since sodium and chloride are present in equal concentrations in dietary salt, chloride test strips may provide a suitable proxy for at-home measurement of urine sodium concentrations. We aimed to determine whether (i) chloride test strips provide a reliable measure of urinary sodium compared to the gold standard flame photometry and (ii) multiple spot samples accurately reflect 24-h urine sodium. We recruited 43 participants (19 males) aged 23.6 ± 0.6 years to complete multiple consecutive spot samples (morning and evening) along with a 24-h urine sodium collection. Urine 24-h sodium estimates using chloride test strips (114.6 ± 7.5 mmol/day) were highly correlated (r = 0.900, p < 0.0001) with flame photometry (121.1 ± 7.7 mmol/day) with a bias of -6.53 ± 22.2 mmol/day. Use of a three-spot sample average (both morning and evening spot samples) with a correction factor applied (122.9 ± 4.1 mmol/day) provided a good approximation of 24-h sodium measured by flame photometry (125.6 ± 9.0 mmol/day), with a bias of -2.55 ± 43.9 mmol/day. Chloride test strips applied to a 24-h urine collection provide a highly accurate measure of urinary sodium excretion, permitting convenient at-home sample collection and analysis. Their application to multiple spot samples provides a reasonable approximation of sodium excretion that can be used to conveniently monitor attempts at dietary sodium manipulation, without the inconvenience of completing a 24-h urine sample., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.

High-level spinal cord injury (SCI) can disrupt cardiovascular autonomic function. However, the evolution of cardiovascular autonomic function in the acute phase following injury is unknown. We evaluated the timing, severity, progression, and implications of cardiovascular autonomic injury following acute SCI. We tested 63 individuals with acute traumatic SCI (aged 48 ± 2 years) at five time-points: <2 weeks, and 1, 3, 6-12, and >12 months post-injury. Supine beat-to-beat systolic arterial pressure (SAP) and R-R interval (RRI) were recorded and low-frequency variability (LF SAP and LF RRI) determined. Cross-spectral analyses were used to determine baroreflex function (low frequency) and cardiorespiratory interactions (high frequency). Known electrocardiographic (ECG) markers for arrhythmia and self-reported symptoms of cardiovascular dysfunction were determined. Comparisons were made with historical data from individuals with chronic SCI and able-bodied controls. Most individuals had high-level (74%) motor/sensory incomplete (63%) lesions. All participants had decreased LF SAP at <2 weeks (2.22 ± 0.65 mm Hg 2 ). Autonomic injury was defined as high-level SCI with LF SAP <2 mm Hg 2 . Two distinct groups emerged by 1 month: autonomically complete SCI with sustained low LF SAP (0.76 ± 0.17 mm Hg 2 ) and autonomically incomplete SCI with increased LF SAP (5.46 ± 1.0 mm Hg 2 , p  < 0.05). Autonomically complete injuries did not recover over time. Cardiovascular symptoms were prevalent and worsened with time, especially in those with autonomically complete lesions, and chronic SCI. Baroreflex function and cardiorespiratory interactions were impaired after SCI. Risk of arrhythmia increased immediately after SCI, and remained elevated throughout the acute phase. Acute SCI is associated with severe cardiovascular dysfunction. LF SAP provides a simple, non-invasive, translatable, quantitative assessment of autonomic function, and is most informative 1 month after injury.

COVID-19 is a global pandemic that is wreaking havoc with the health and economy of much of human civilization. In this document from the American Autonomic Society, we identify the potential risks of exposure to patients, physicians, and allied healthcare staff. We provide guidance for conducting autonomic function testing safely in this environment.

Human ether-à-go-go related gene (hERG) K + channels are important in cardiac repolarization, and their dysfunction causes prolongation of the ventricular action potential, long QT syndrome, and arrhythmia. As such, approaches to augment hERG channel function, such as activator compounds, have been of significant interest due to their marked therapeutic potential. Activator compounds that hinder channel inactivation abbreviate action potential duration (APD) but carry risk of overcorrection leading to short QT syndrome. Enhanced risk by overcorrection of the APD may be tempered by activator-induced increased refractoriness; however, investigation of the cumulative effect of hERG activator compounds on the balance of these effects in whole organ systems is lacking. Here, we have investigated the antiarrhythmic capability of a hERG activator, RPR260243, which primarily augments channel function by slowing deactivation kinetics in ex vivo zebrafish whole hearts. We show that RPR260243 abbreviates the ventricular APD, reduces triangulation, and steepens the slope of the electrical restitution curve. In addition, RPR260243 increases the post-repolarization refractory period. We provide evidence that this latter effect arises from RPR260243-induced enhancement of hERG channel-protective currents flowing early in the refractory period. Finally, the cumulative effect of RPR260243 on arrhythmogenicity in whole organ zebrafish hearts is demonstrated by the restoration of normal rhythm in hearts presenting dofetilide-induced arrhythmia. These findings in a whole organ model demonstrate the antiarrhythmic benefit of hERG activator compounds that modify both APD and refractoriness. Furthermore, our results demonstrate that targeted slowing of hERG channel deactivation and enhancement of protective currents may provide an effective antiarrhythmic approach. NEW & NOTEWORTHY hERG channel dysfunction causes long QT syndrome and arrhythmia. Activator compounds have been of significant interest due to their therapeutic potential. We used the whole organ zebrafish heart model to demonstrate the antiarrhythmic benefit of the hERG activator, RPR260243. The activator abbreviated APD and increased refractoriness, the combined effect of which rescued induced ventricular arrhythmia. Our findings show that the targeted slowing of hERG channel deactivation and enhancement of protective currents caused by the RPR260243 activator may provide an effective antiarrhythmic approach.

Study Design: Clinical trial., Objective: Spinal cord injury (SCI) impacts autonomic function and bowel management. Bowel care is a potential trigger for autonomic dysreflexia (AD; paroxysmal hypertension elicited by sensory stimuli below the level of lesion). AD can be life threatening so strategies to minimise AD are prioritised after SCI. Lidocaine lubricant is recommended during bowel care with the rationale to minimise the sensory stimulus, reducing AD. The objective of this study was to assess whether lidocaine lubricant (Xylocaine 2%) ameliorates AD during at-home bowel care compared with standard lubricant (placebo)., Setting: Community., Method: Participants (n = 13; age 44.0 ± 3.3 years) with high-level SCI (C3-T4) performed their normal at-home bowel care on two days, each time using a different lubricant, with continuous non-invasive cardiovascular monitoring. Injury to spinal autonomic (sympathetic) nerves was determined from low-frequency systolic arterial pressure (LF SAP) variability., Results: Participants displayed reduced autonomic function (LF SAP 3.02 ± 0.84 mmHg 2 ), suggesting impaired autonomic control. Bowel care duration was increased with lidocaine (79.1 ± 10.0 min) compared to placebo (57.7 ± 6.3 min; p = 0.018). All participants experienced AD on both days, but maximum SAP was higher with lidocaine (214.3 ± 10.5 mmHg) than placebo (196.7 ± 10.0 mmHg; p = 0.046). Overall, SAP was higher for longer with lidocaine (6.5 × 10 5  ± 0.9 × 10 5  mmHg • beat) than placebo (4.4 × 10 5  ± 0.6 × 10 5  mmHg • beat; p = 0.018) indicating a higher burden of AD. Heart rate and rhythm disturbances were increased during AD, particularly with lidocaine use., Conclusions: At-home bowel care was a potent trigger for AD. Our findings contradict recommendations for lidocaine use during bowel care, suggesting that anaesthetic lubricants impair reflex bowel emptying, resulting in longer care routines with an increased burden of AD.

Introduction: Human papillomavirus (HPV) vaccination has been anecdotally connected to the development of dysautonomia, chronic fatigue, complex regional pain syndrome and postural tachycardia syndrome., Objectives: To critically evaluate a potential connection between HPV vaccination and the above-noted conditions., Methods: We reviewed the literature containing the biology of the virus, pathophysiology of infection, epidemiology of associated cancers, indications of HPV vaccination, safety surveillance data and published reports linking HPV vaccination to autonomic disorders., Results: At this time, the American Autonomic Society finds that there are no data to support a causal relationship between HPV vaccination and CRPS, chronic fatigue, and postural tachycardia syndrome to other forms of dysautonomia., Conclusion: Certain conditions are prevalent in the same populations that are vaccinated with the HPV vaccine (peri-pubertal males and females). This association, however, is an insufficient proof of causality.

Orthostatic fluid shifts reduce the effective circulating volume and thus contribute to syncope susceptibility. Recurrent syncope has a devastating impact on quality of life and is challenging to manage effectively. To blunt orthostatic fluid shifts, static calf compression garments are often prescribed to patients with syncope, but have questionable efficacy. Intermittent calf compression, which mimics the skeletal muscle pump to minimize pooling and filtration, holds promise for the management of syncope. We aimed to evaluate the effectiveness of intermittent calf compression for increasing orthostatic tolerance (OT; time to presyncope). We conducted a randomized single-blind crossover study, in which participants ( n = 21) underwent three graded 60° head-up-tilt tests to presyncope with combined lower body negative pressure on separate days. Low frequency intermittent calf compression (ICLF; 4 s on and 11 s off) at 0-30 and 0-60 mmHg was applied during two tests and compared to a placebo condition where the garment was fitted, but no compression applied. We measured continuous leg circumference changes (strain gauge plethysmography), cardiovascular responses (finger plethysmography; Finometer Pro), end tidal gases (nasal cannula), and cerebral blood flow velocity (CBFv, transcranial Doppler). The 0-60 mmHg ICLF increased OT (33 ± 2.2 min) compared to both placebo (26 ± 2.4 min; p < 0.001) and 0-30 mmHg ICLF (25 ± 2.7 min; p < 0.001). Throughout testing 0-60 mmHg ICLF reduced orthostatic fluid shifts compared to both placebo and 0-30 mmHg ICLF ( p < 0.001), with an associated improvement in stroke volume ( p < 0.001), allowing blood pressure to be maintained at a reduced heart rate ( p < 0.001). In addition, CBFv was higher with 0-60 mmHg ICLF than 0-30 mmHg ICLF and placebo ( p < 0.001). Intermittent calf compression is a promising novel intervention for the management of orthostatic intolerance, which may provide affected individuals renewed independence and improved quality of life., (Copyright © 2020 Hockin and Claydon.)

Background: The upright posture imposes a significant challenge to blood pressure regulation that is compensated through baroreflex-mediated increases in heart rate and vascular resistance. Orthostatic cardiac responses are easily inferred from heart rate, but vascular resistance responses are harder to elucidate. One approach is to determine vascular resistance as arterial pressure/blood flow, where blood flow is inferred from ultrasound-based measurements of brachial blood velocity. This relies on the as yet unvalidated assumption that brachial artery diameter does not change during orthostatic stress, and so velocity is proportional to flow. It is also unknown whether the orthostatic vascular resistance response is related to initial blood vessel diameter., Methods: We determined beat-to-beat heart rate (ECG), blood pressure (Portapres) and vascular resistance (Doppler ultrasound) during a combined orthostatic stress test (head-upright tilting and lower body negative pressure) continued until presyncope. Participants were 16 men (aged 38.4±2.3 years) who lived permanently at high altitude (4450m)., Results: The supine brachial diameter ranged from 2.9-5.6mm. Brachial diameter did not change during orthostatic stress (supine: 4.19±0.2mm; tilt: 4.20±0.2mm; -20mmHg lower body negative pressure: 4.19±0.2mm, p = 0.811). There was no significant correlation between supine brachial artery diameter and the maximum vascular resistance response (r = 0.323; p = 0.29). Forearm vascular resistance responses evaluated using brachial arterial flow and velocity were strongly correlated (r = 0.989, p<0.00001) and demonstrated high equivalency with minimal bias (-6.34±24.4%)., Discussion: During severe orthostatic stress the diameter of the brachial artery remains constant, supporting use of brachial velocity for accurate continuous non-invasive orthostatic vascular resistance responses. The magnitude of the orthostatic forearm vascular resistance response was unrelated to the baseline brachial arterial diameter, suggesting that upstream vessel size does not matter in the ability to mount a vasoconstrictor response to orthostasis., Competing Interests: The authors have declared that no competing interests exist.

Puberty is initiated by hormonal changes in the adolescent body that trigger physical and behavioral changes to reach adult maturation. As these changes occur, some adolescents experience concerning pubertal symptoms that are associated with dysfunction of the autonomic nervous system (ANS). Vasovagal syncope (VVS) and Postural Orthostatic Tachycardia Syndrome (POTS) are common disorders of the ANS associated with puberty that are related to orthostatic intolerance and share similar symptoms. Compared to young males, young females have decreased orthostatic tolerance and a higher incidence of VVS and POTS. As puberty is linked to changes in specific sex and non-sex hormones, and hormonal therapy sometimes improves orthostatic symptoms in female VVS patients, it is possible that pubertal hormones play a role in the increased susceptibility of young females to autonomic dysfunction. The purpose of this paper is to review the key hormonal changes associated with female puberty, their effects on the ANS, and their potential role in predisposing some adolescent females to cardiovascular autonomic dysfunctions such as VVS and POTS. Increases in pubertal hormones such as estrogen, thyroid hormones, growth hormone, insulin, and insulin-like growth factor-1 promote vasodilatation and decrease blood volume. This may be exacerbated by higher levels of progesterone, which suppresses catecholamine secretion and sympathetic outflow. Abnormal heart rate increases in POTS patients may be exacerbated by pubertal increases in leptin, insulin, and thyroid hormones acting to increase sympathetic nervous system activity and/or catecholamine levels. Given the coincidental timing of female pubertal hormone surges and adolescent onset of VVS and POTS in young women, coupled with the known roles of these hormones in modulating cardiovascular homeostasis, it is likely that female pubertal hormones play a role in predisposing females to VVS and POTS during puberty. Further research is necessary to confirm the effects of female pubertal hormones on autonomic function, and their role in pubertal autonomic disorders such as VVS and POTS, in order to inform the treatment and management of these debilitating disorders., (Copyright © 2019 Coupal, Heeney, Hockin, Ronsley, Armstrong, Sanatani and Claydon.)

Background and Purpose- Traditional risk factors for ischemic stroke are body stressors that are related to autonomic autonomic system (ANS) dysfunction. The value of ABCD2 score (age, blood pressure, clinical features, duration of symptoms, diabetes) to predict ischemic stroke after transient ischemic attack is compromised by the inclusion of a limited number of stressors. We aimed to assess whether markers of ANS function and stress could predict the occurrence of secondary ischemic events after transient ischemic attack or minor stroke. Methods- This is a prospective cohort study in which 201 patients were recruited within 48 hours after initial transient ischemic attack or minor stroke and followed for 90 days to assess the development of secondary ischemic events. ABCD2 score, heart rate variability (HRV) parameters as markers of ANS function, and psychological stress were assessed. Logistic regression and area under the curve (AUC) were used to assess the models' predictive ability. Results- Morning high frequency (HF) HRV power and changes in HF HRV from morning to afternoon (daytime HF changes) were the most useful HRV predictors for both ischemic events (AUC=0.61 and 0.70) and ischemic stroke (AUC=0.62 and 0.72). Compared with ABCD2 score, 2 HRV-based stress models showed higher predictive ability for ischemic events (AUC=0.82 versus 0.63, 0.76 versus 0.63; P<0.05) and ischemic stroke (AUC=0.87 versus 0.64, 0.82 versus 0.64; P<0.05). Conclusions- Assessing the effects of stress on the ANS may be an innovative way to stratify the risk of ischemic events after transient ischemic attack or minor stroke. New risk stratification by assessing the dynamic features of ANS dysfunction and stress may help identify high-risk sub-populations that may benefit from added management.

Background: Continuous beat-to-beat blood pressure monitoring permits the rapid detection of blood pressure fluctuations for cardiovascular reflex testing and clinical haemodynamic monitoring. In adults, this can be achieved noninvasively with high accuracy, using finger blood pressure monitoring with volume clamp photoplethysmography. However, data are lacking on the validity of finger blood pressure monitoring in children compared to the gold standard - invasive intra-arterial blood pressure monitoring., Aim: We aimed to evaluate the accuracy of novel noninvasive index and middle finger arterial pressure (FinAP) measurements in children., Methods: Using prototype paediatric finger cuffs, we compared: mean differences, bias and limits of agreement (Bland-Altman analyses); cumulative percentage differences [clinical grade A-D (based on the percentage of heartbeats in agreement with the standard)]; and waveform morphology (regression analysis and smoothing) between both raw FinAP (Finapres NOVA) and reconstructed finger-brachial arterial pressure (reBAP) compared to intra-arterial blood pressure measurements., Results: Eighteen children were tested (aged 3-13 years; 12 male), with data from 13 included in the analysis. The bias for reBAP for the middle finger was 1.8±6.9, 0.3±6.1 and 0.4±5.3 mmHg for systolic, diastolic and mean arterial pressure, with clinical grades of C, B and A, respectively. reBAP improved numerical accuracy, but reduced waveform morphological agreement., Conclusion: Middle finger arterial measurements with waveform reconstruction provide an acceptable surrogate for invasive intra-arterial recording in children. Finger blood pressure monitoring is a novel comfortable, convenient and accurate alternative approach for noninvasive beat-to-beat blood pressure monitoring in children.

Background: Orthostatic hypotension (OH; profound falls in blood pressure when upright) is a common deficit that increases in incidence with age, and may be associated with falling risk. Deficit accumulation results in frailty, regarded as enhanced vulnerability to adverse outcomes. We aimed to evaluate the relationships between OH, frailty, falling and mortality in elderly care home residents., Methods: From the Minimum Data Set (MDS) document, a frailty index (FI-MDS) was generated from a list of 58 deficits, ranging from 0 (no deficits) to 1.0 (58 deficits). OH was evaluated from beat-to-beat blood pressure and heart rate (finger plethysmography) collected during a 15-min supine-seated orthostatic stress test. Retrospective and prospective falling rates (falls/year) were extracted from facility falls incident reports. All-cause 3-year mortality was determined. Data are reported as mean ± standard error., Results: Data were obtained from 116 older adults (aged 84.2 ± 0.9 years; 44% males) living in two long term care facilities. The mean FI-MDS was 0.36 ± 0.01; FI-MDS was correlated with age (r = 0.277; p = 0.003). Those who were frail (FI ≥ 0.27) had larger Initial (- 17.8 ± 4.2 vs - 6.1 ± 3.3 mmHg, p = 0.03) and Consensus (- 22.7 ± 4.3 vs - 11.5 ± 3.3 mmHg, p = 0.04) orthostatic reductions in systolic arterial pressure. Frail individuals had higher prospective and retrospective falling rates and higher 3-year mortality. Receiver operating characteristic curves evaluated the ability of FI-MDS alone to predict prospective falls (sensitivity 72%, specificity 36%), Consensus OH (sensitivity 68%, specificity 60%) and 3-year mortality (sensitivity 77%, specificity 49%). Kaplan Meier survival analyses showed significantly higher 3-year mortality in those who were frail compared to the non-frail (p = 0.005)., Conclusions: Frailty can be captured using a frailty index based on MDS data in elderly individuals living in long term care, and is related to susceptibility to orthostatic hypotension, falling risk and 3-year mortality. Use of the MDS to generate a frailty index may represent a simple and convenient risk assessment tool for older adults living in long term care. Older adults who are both frail and have impaired orthostatic blood pressure control have a particularly high risk of falling and should receive tailored management to mitigate this risk.

When upright, venous pooling and capillary filtration reduce the effective circulating volume and are key contributors to susceptibility to syncope (fainting). Recurrent syncope has a devastating impact on quality of life. Static calf compression garments are frequently prescribed for patients with syncope, but have questionable efficacy. Intermittent calf compression, which mimics the skeletal muscle pump to minimize pooling and filtration, is a potential alternative that holds promise for the management of syncope. We aimed to evaluate use of intermittent calf compression compared to commonly prescribed compression stockings, and determine the optimal intermittent calf compression paradigm, for improvement of orthostatic fluid shifts and cardiovascular control. We evaluated heart rate, blood pressure, stroke volume, cardiac output and peripheral resistance (finger plethysmography with Modelflow™) and calf pooling and filtration (calf circumference; strain gauge plethysmography) during a series of 10-min head-upright tilts. We first compared (protocol one) low (ICLF; 4 s on, 11 s off) and high (ICHF; 4 s on, 6 s off) frequency 0-100 mm Hg intermittent calf compression with static elastic and inelastic compression stockings and a placebo condition (n = 19, 5 males, aged 23.5 ± 0.1 years). We then compared (protocol two) ICLF applied at 0-40 mm Hg, 0-60 mm Hg, 0-80 mm Hg and 0-100 mm Hg as well as a placebo condition (n = 15, 5 males, aged 22.7 ± 0.5 years). The intervention order was randomized. In protocol one, all compression conditions significantly reduced calf circumference (p < 0.001) compared to placebo after 10-min upright; however, this reduction was greater in ICLF (-0.88 ± 0.18%) and ICHF (-1.14 ± 0.21%) conditions than both elastic (+0.49 ± 0.17%) and inelastic (-0.01 ± 0.19%) compression (p < 0.001). ICLF and ICHF, but not elastic or inelastic compression, were associated with improved stroke volume (p ≤ 0.001), allowing cardiac output to be maintained at a reduced heart rate (p < 0.001) without increases in vascular resistance responses, increasing hemodynamic reserve. ICHF showed no significant benefit over ICLF, evidenced by the lack of significant difference between ICLF and ICHF in any parameter measured. In protocol two, 0-60 mm Hg ICLF was considered the optimal intermittent compression because it was the lowest pressure that abolished the increase in calf circumference during orthostasis, while improving SV (p = 0.002), and reducing HR (p < 0.001) throughout tilt. Intermittent calf compression from 0 to 60 mm Hg ICLF is the optimal intermittent compression paradigm to ameliorate orthostatic fluid shifts and improve hemodynamic control. Commonly prescribed static calf compression garments do not improve orthostatic cardiovascular responses., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cardiovascular autonomic dysfunction is an early marker for cardiovascular disease. Anthracycline chemotherapy and left-sided radiation for breast cancer are associated with negative autonomic function changes. This study's objectives were to characterize changes in, and the association of exercise training with, clinical indices of cardiovascular autonomic function across the trajectory of breast cancer therapy., Subjects, Materials, and Methods: Seventy-three patients receiving adjuvant chemotherapy participated to varying degrees in supervised aerobic and resistance exercise during chemotherapy ± radiation and for 20 weeks after. Resting heart rate (HR rest ) and blood pressure were measured weekly during chemotherapy. HR rest , exercise heart rate recovery (HR recovery ), and aerobic fitness were measured at enrollment, end of chemotherapy ± radiation, and 10 and 20 weeks after treatment., Results: During chemotherapy, HR rest increased in a parabolic manner within a single treatment and with increasing treatment dose, whereas systolic and diastolic blood pressure decreased linearly across treatments. Tachycardia and hypotension were present in 32%-51% of participants. Factors associated with weekly changes during chemotherapy included receiving anthracyclines or trastuzumab, days since last treatment, hematocrit, and exercise attendance. Receipt of anthracyclines, trastuzumab, and left-sided radiation individually predicted impairments of HR rest and HR recovery during chemotherapy ± radiation; however, aerobic fitness change and at least twice-weekly exercise attendance predicted improvement. By 10 weeks after treatment, HR rest and blood pressure were not different from prechemotherapy., Conclusion: In this study, chemotherapy resulted in increased HR rest and tachycardia, as well as decreased blood pressure and hypotension. Anthracyclines, trastuzumab, and left-sided radiation were associated with HR rest elevations and impairments of HR recovery , but exercise training at least twice a week appeared to mitigate these changes., Implications for Practice: This study characterized changes in clinically accessible measures with well-established prognostic value for cardiovascular disease, and investigated associations with cardiotoxic treatments and the positive influence of exercise. The chemotherapy-related incremental increase in resting heart rate, with tachycardia occurring in one third of patients, and decrease in blood pressure, with hypotension occurring in one half of the patients, is relevant to oncology practitioners for clinical examination or patient report of related symptoms (i.e., dizziness). The weekly dose of two 60-minute sessions of moderate-intensity aerobic and resistance exercise that was identified as protective of cardiovascular autonomic impairments can easily be prescribed to patients by oncologists., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Autonomic dysfunction is common in individuals with spinal cord injury (SCI) and leads to numerous abnormalities, including profound cardiovascular and bowel dysfunction. In those with high-level lesions, bowel management is a common trigger for autonomic dysreflexia (AD; hypertension provoked by sensory stimuli below the injury level). Improving bowel care is integral for enhancing quality of life (QoL). We aimed to describe the relationships between bowel care, AD, and QoL in individuals with SCI. We performed an online community survey of individuals with SCI. Those with injury at or above T7 were considered at risk for AD. Responses were received from 287 individuals with SCI (injury levels C1-sacral and average duration of injury 17.1 ± 12.9 [standard deviation] years). Survey completion rate was 73% (n = 210). Bowel management was a problem for 78%: it interfered with personal relationships (60%) and prevented staying (62%) and working (41%) away from home. The normal bowel care duration was >60 min in 24% and most used digital rectal stimulation (59%); 33% reported bowel incontinence at least monthly. Of those at risk for AD (n = 163), 74% had AD symptoms during bowel care; 32% described palpitations. AD interfered with activities of daily living in 51%. Longer durations of bowel care (p < 0.001) and more severe AD (p = 0.04) were associated with lower QoL. Bowel management is a key concern for individuals with SCI and is commonly associated with symptoms of AD. Further studies should explore ways to manage bowel dysfunction, increase self-efficacy, and ameliorate the impact of AD to improve QoL.

Transient ischemic attack (TIA) and minor stroke have high risks of recurrence and deterioration into severe ischemic strokes. Risk stratification of TIA and minor stroke is essential for early effective treatment. Traditional tools have only moderate predictive value, likely due to their inclusion of the limited number of stroke risk factors. Our review follows Hans Selye's fundamental work on stress theory and the progressive shift of the autonomic nervous system (ANS) from adaptation to disease when stress becomes chronic. We will first show that traditional risk factors and acute triggers of ischemic stroke are chronic and acute stress factors or "stressors," respectively. Our first review shows solid evidence of the relationship between chronic stress and stroke occurrence. The stress response is tightly regulated by the ANS whose function can be assessed with heart rate variability (HRV). Our second review demonstrates that stress-related risk factors of ischemic stroke are correlated with ANS dysfunction and impaired HRV. Our conclusions support the idea that HRV parameters may represent the combined effects of all body stressors that are risk factors for ischemic stroke and, thus, may be of important predictive value for the risk of subsequent ischemic events after TIA or minor stroke.