Hemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular regulation. The aim of this study was to explore blood pressure variability and closed-loop baroreflex function at rest and during mild orthostatic stress in adolescents with CFS. We included a consecutive sample of 14 adolescents 12–18 years old with CFS diagnosed according to a thorough and standardized set of investigations and 56 healthy control subjects of equal sex and age distribution. Heart rate and blood pressure were recorded continuously and non-invasively during supine rest and during lower body negative pressure (LBNP) of –20 mmHg to simulate mild orthostatic stress. Indices of blood pressure variability and baroreflex function (α-gain) were computed from monovariate and bivariate spectra in the low-frequency (LF) band (0.04–0.15 Hz) and the high–frequency (HF) band (0.15–0.50 Hz), using an autoregressive algorithm. Variability of systolic blood pressure in the HF range was lower among CFS patients as compared to controls both at rest and during LBNP. During LBNP, compared to controls, α-gain HF decreased more, and α-gain LF and the ratio of α-gain LF/α-gain HF increased more in CFS patients, all suggesting greater shift from parasympathetic to sympathetic baroreflex control. CFS in adolescents is characterized by reduced systolic blood pressure variability and a sympathetic predominance of baroreflex heart rate control during orthostatic stress. These findings may have implications for the pathophysiology of CFS in adolescents.
Blood pressure variability; Baroreflex sensitivity; Chronic fatigue syndrome; Autonomic nervous system; Cardiovascular regulation
Hemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular regulation. The aim of this study was to explore blood pressure variability and closed-loop baroreflex function at rest and during mild orthostatic stress in adolescents with CFS.
We included a consecutive sample of 14 adolescents 12 to 18 years old with CFS diagnosed according to a thorough and standardized set of investigations, and 56 healthy control subjects of equal sex and age distribution. Heart rate and blood pressure were recorded continuously and non-invasively during supine rest and during lower body negative pressure (LBNP) of −20 mm Hg to simulate mild orthostatic stress. Indices of blood pressure variability and baroreflex function (α-gain) were computed from monovariate and bivariate spectra in the low-frequency (LF) band (0.04–0.15 Hz) and the high-frequency (HF) band (0.15–0.50 Hz), using an autoregressive algorithm.
Variability of systolic blood pressure in the HF range was lower among CFS patients as compared to controls both at rest and during LBNP. During LBNP compared to controls, α-gain HF decreased more, and α-gain LF and the ratio of α-gain LF/α-gain HF increased more in CFS patients, all suggesting greater shift from parasympathetic to sympathetic baroreflex control.
CFS in adolescents is characterized by reduced systolic blood pressure variability, and a sympathetic predominance of baroreflex heart rate control during orthostatic stress. These findings may have implications for the pathophysiology of CFS in adolescents.
Blood pressure variability; baroreflex sensitivity; chronic fatigue syndrome; autonomic nervous system; cardiovascular regulation
OBJECTIVES—Patients with chronic fatigue syndrome
complain of physical and mental fatigue that is worsened by exertion.
It was predicted that the cognitive and motor responses to vigorous
exercise in patients with chronic fatigue syndrome would differ from
those in depressed and healthy controls.
METHODS—Ten patients with chronic fatigue
syndrome, 10 with depressive illness, and 10 healthy controls completed
cognitive and muscle strength testing before and after a treadmill
exercise test. Measures of cardiovascular functioning and perceived
effort, fatigue, and mood were taken during each stage of testing.
RESULTS—Depressed patients performed worst on
cognitive tests at baseline. During the treadmill test, patients with
chronic fatigue syndrome had higher ratings of perceived effort and
fatigue than both control groups, whereas patients with depression
reported lower mood. After exertion, patients with chronic fatigue
syndrome showed a greater decrease than healthy controls on everyday
tests of focused (p=0.02) and sustained (p=0.001) attention, as well as
greater deterioration than depressed patients on the focused attention
task (p=0.03). No between group differences were found in
cardiovascular or symptom measures taken during the cognitive testing.
CONCLUSIONS—Patients with chronic fatigue syndrome
show a specific sensitivity to the effects of exertion on effortful
cognitive functioning. This occurs despite subjective and objective
evidence of effort allocation in chronic fatigue syndrome, suggesting
that patients have reduced working memory capacity, or a greater demand
to monitor cognitive processes, or both. Further insight into the
pathophysiology of the core complaints in chronic fatigue syndrome is
likely to be realised by studying the effects of exercise on other
aspects of everyday functioning.
BACKGROUND: In chronic autonomic failure of varying aetiologies, there are differences in the cardiovascular responses to supine leg exercise and to standing after exercise. Whether this occurs between the different subgroups with Shy-Drager syndrome (SDS) is unknown. METHODS: Fourteen patients with the cerebellar form (SDS-C) and 11 patients with parkinsonian features (SDS-P) were studied. RESULTS: Both groups had a similar degree of autonomic failure and postural hypotension. Their responses were compared with nine patients with idiopathic Parkinson's disease (IPD) and 15 normal subjects (controls), all with normal autonomic function. With supine exercise, blood pressure and heart rate rose similarly in controls and patients with IPD and there was no fall in blood pressure on standing after exercise. In both SDS groups there were abnormal responses to exercise: blood pressure fell in SDS-C, but did not fall or rise in SDS-P. Heart rate increased similarly in both SDS groups, calculated systemic vascular resistance fell similarly, but cardiac index rose more in SDS-P than SDS-C. Resting plasma noradrenaline concentrations were subnormal in both forms of SDS, and did not increase with exercise. Postural hypotension was enhanced after exercise to the same extent in SDS-C and SDS-P. CONCLUSIONS: The greater cardiovascular abnormalities in response to exercise in SDS-C suggests that cerebellar or brain stem autonomic pathways are impaired to a greater extent in SDS-C than in SDS-P. Pooling SDS subgroups, therefore, may obscure pathophysiological differences to certain stimuli. Clinically when postural hypotension is being assessed, separation of the subgroups may not be essential, as they responded similarly.
There is an increasing interest in developing school programs that improve the ability of children to cope with psychosocial stress. Yoga may be an appropriate intervention as it has demonstrated improvements in the ability of children to manage psychosocial stress. Yoga is thought to improve the control of reactivity to stress via the regulation of the autonomic nervous system. The current study examined the effects of yoga compared to a physical education class on physiological response (blood pressure (BP) and heart rate (HR)) to behavioral stressor tasks (mental arithmetic and mirror tracing tasks). Data analysis of BP and HR was performed using a 2 × 2 × 4 repeated measures ANOVA (time × group × stressor time points). 30 (17 male) 6th graders participated in the study. Yoga did not provide significant differences in stress reactivity compared to a physical education class (group × time: systolic (F(1,28) = .538, P = .470); diastolic (F(1,28) = .1.061, P = .312); HR (F(1,28) = .401, P = .532)). The lack of significant differences may be due to the yoga intervention failing to focus on stress management and/or the stressor tasks not adequately capturing attenuation of stressor response.
OBJECTIVE: To investigate the role of the autonomic nervous system in determining QT interval and dispersion. PATIENTS AND METHODS: 32 patients with chronic primary (idiopathic) autonomic failure (19 men, mean age 60 years) and 21 normal controls (11 men, mean age 59) without symptoms of ischaemic heart disease were studied retrospectively. Autonomic failure was diagnosed by a combination of symptomatic postural hypotension, subnormal plasma noradrenaline response to head-up tilt, and abnormal cardiovascular responses to standing, Valsalva manoeuvre, mental stress, cutaneous cold, isometric exercise, and deep breathing. QT intervals were measured from surface electrocardiograms and QT dispersion was defined as maximum QT--minimum QT occurring in any of the 12 leads. RESULTS: Mean heart rate (RR intervals) was similar in patients with autonomic failure and controls (S2 lead: 865 (132) v 857 (108) ms, P = NS; V2 lead: 865 (130) v 868 (113) ms, P = NS). QT intervals measured from electrocardiogram leads S2 and V2 were significantly longer in patients than in controls (401 (40) v 376 (16) ms, P < 0.01; and 403 (41) v 381 (20) ms, P < 0.05 respectively). The mean maximum QT interval in any lead, which is the best estimate of the maximum duration of electrical systole, was significantly longer in the patients than in controls (417 (48) v 388 (23) ms, P < 0.005). Linear regression analysis of QT and RR intervals for both groups showed a significant difference between the slopes of the two regression lines (F = 8.4, P < 0.001). However, QT dispersions were similar between patients and controls. CONCLUSIONS: Patients with primary autonomic failure have prolongation of QT intervals, indicating that the autonomic nervous system is an important determinant of QT interval. However, QT dispersion does not seem to be affected by chronic primary autonomic denervation.
Acute mental stress may contribute to the cardiovascular disease progression via autonomic nervous system controlled negative effects on the endothelium. The joint effects of stress-induced sympathetic or parasympathetic activity and endothelial function on atherosclerosis development have not been investigated. The present study aims to examine the interactive effect of acute mental stress-induced cardiac reactivity/recovery and endothelial function on the prevalence of carotid atherosclerosis.
Participants were 81 healthy young adults aged 24-39 years. Preclinical atherosclerosis was assessed by carotid intima-media thickness (IMT) and endothelial function was measured as flow-mediated dilatation (FMD) using ultrasound techniques. We also measured heart rate, respiratory sinus arrhythmia (RSA), and pre-ejection period (PEP) in response to the mental arithmetic and speech tasks.
We found a significant interaction of FMD and cardiac RSA recovery for IMT (p = 0.037), and a significant interaction of FMD and PEP recovery for IMT (p = 0.006). Among participants with low FMD, slower PEP recovery was related to higher IMT. Among individuals with high FMD, slow RSA recovery predicted higher IMT. No significant interactions of FMD and cardiac reactivity for IMT were found.
Cardiac recovery plays a role in atherosclerosis development in persons with high and low FMD. The role of sympathetically mediated cardiac activity seems to be more important in those with impaired FMD, and parasympathetically mediated in those with relatively high FMD. The development of endothelial dysfunction may be one possible mechanism linking slow cardiac recovery and atherosclerosis via autonomic nervous system mediated effect.
Postural tachycardia syndrome (POTS), characterized by orthostatic tachycardia in the absence of orthostatic hypotension, has been the focus of increasing clinical interest over the last 15 years 1. Patients with POTS complain of symptoms of tachycardia, exercise intolerance, lightheadedness, extreme fatigue, headache and mental clouding. Patients with POTS demonstrate a heart rate increase of ≥30 bpm with prolonged standing (5-30 minutes), often have high levels of upright plasma norepinephrine (reflecting sympathetic nervous system activation), and many patients have a low blood volume. POTS can be associated with a high degree of functional disability. Therapies aimed at correcting the hypovolemia and the autonomic imbalance may help relieve the severity of the symptoms. This review outlines the present understanding of the pathophysiology, diagnosis, and management of POTS.
Postural Tachycardia Syndrome; Pathophysiology; Diagnosis; Management
Little is known about normative variation in stress response over the adolescent transition. This study examined neuroendocrine and cardiovascular responses to performance and peer rejection stressors over the adolescent transition in a normative sample. Participants were 82 healthy children (ages 7-12 years, n=39, 22 females) and adolescents (ages 13-17, n=43, 20 females) recruited through community postings. Following a habituation session, participants completed a performance (public speaking, mental arithmetic, mirror tracing) or peer rejection (exclusion challenges) stress session. Salivary cortisol, alpha amylase (sAA), systolic and diastolic blood pressure (SBP, DBP), and heart rate (HR) were measured throughout. Adolescents showed significantly greater cortisol, sAA, SBP and DBP stress response relative to children. Developmental differences were most pronounced in the performance stress session for cortisol and DBP, and in the peer rejection session for sAA and SBP. Heightened physiological stress responses in typical adolescents may facilitate adaptation to new challenges of adolescence and adulthood. In high-risk adolescents, this normative shift may tip the balance toward stress response dysregulation associated with depression and other psychopathology. Specificity of physiological response by stressor type highlights the importance of a multi-system approach to the psychobiology of stress and may also have implications for understanding trajectories to psychopathology.
adolescent; child; stress; cortisol; cardiovascular; amylase; depression
Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS.
Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between–group differences in autonomic reactivity and associations with cognitive performance were analysed.
Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes.
These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity.
It has long been recognized that cardiac autonomic neuropathy increases morbidity and mortality in diabetes and may have greater predictive power than traditional risk factors for cardiovascular events. Significant morbidity and mortality can now be attributable to autonomic imbalance between the sympathetic and parasympathetic nervous system regulation of cardiovascular function. New and emerging syndromes include orthostatic tachycardia, orthostatic bradycardia and an inability to use heart rate as a guide to exercise intensity because of the resting tachycardia. Recent studies have shown that autonomic imbalance may be a predictor of risk of sudden death with intensification of glycaemic control. This review examines an association of autonomic dysregulation and the role of inflammatory cytokines and adipocytokines that promote cardiovascular risk. In addition, conditions of autonomic imbalance associated with cardiovascular risk are discussed. Potential treatment for restoration of autonomic balance is outlined.
strength, aerobic exercise capacity and efficiency, and functional
incapacity in patients with chronic fatigue syndrome (CFS) who do not
have a current psychiatric disorder.
patients with CFS without a current psychiatric disorder, 30 healthy
but sedentary controls, and 15 patients with a current major depressive
disorder were recruited into the study. Exercise capacity and
efficiency were assessed by monitoring peak and submaximal oxygen
uptake, heart rate, blood lactate, duration of exercise, and perceived
exertion during a treadmill walking test. Strength was measured using
twitch interpolated voluntary isometric quadriceps contractions.
Symptomatic measures included physical and mental fatigue, mood, sleep,
somatic amplification, and functional incapacity.
sedentary controls, patients with CFS were physically weaker, had a
significantly reduced exercise capacity, and perceived greater effort
during exercise, but were equally unfit. Compared with depressed
controls, patients with CFS had significantly higher submaximal oxygen
uptakes during exercise, were weaker, and perceived greater physical
fatigue and incapacity. Multiple regression models suggested that
exercise incapacity in CFS was related to quadriceps muscle weakness,
increased cardiovascular response to exercise, and body mass index. The
best model of the increased exercise capacity found after graded
exercise therapy consisted of a reduction in submaximal heart rate
response to exercise.
with CFS were weaker than sedentary and depressed controls and as unfit
as sedentary controls. Low exercise capacity in patients with CFS was
related to quadriceps muscle weakness, low physical fitness, and a high
body mass ratio. Improved physical fitness after treatment was
associated with increased exercise capacity. These data imply that
physical deconditioning helps to maintain physical disability in CFS
and that a treatment designed to reverse deconditioning helps to
improve physical function.
There are no studies of autonomic function comparing Alzheimer's disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD).
To assess cardiovascular autonomic function in 39 patients with AD, 30 with VAD, 30 with DLB, 40 with PDD and 38 elderly controls by Ewing's battery of autonomic function tests and power spectral analysis of heart rate variability. To determine the prevalence of orthostatic hypotension and autonomic neuropathies by Ewing's classification.
There were significant differences in severity of cardiovascular autonomic dysfunction between the four types of dementia. PDD and DLB had considerable dysfunction. VAD showed limited evidence of autonomic dysfunction and in AD, apart from orthostatic hypotension, autonomic functions were relatively unimpaired. PDD showed consistent impairment of both parasympathetic and sympathetic function tests in comparison with controls (all p<0.001) and AD (all p<0.03). DLB showed impairment of parasympathetic function (all p<0.05) and one of the sympathetic tests in comparison with controls (orthostasis; p = 0.02). PDD had significantly more impairment than DLB in some autonomic parameters (Valsalva ratio: p = 0.024; response to isometric exercise: p = 0.002). Patients with VAD showed impairment in two parasympathetic tests (orthostasis: p = 0.02; Valsalva ratio: p = 0.08) and one sympathetic test (orthostasis: p = 0.04). These results were in contrast with AD patients who only showed impairment in one sympathetic response (orthostasis: p = 0.004). The prevalence of orthostatic hypotension and autonomic neuropathies was higher in all dementias than in controls (all p<0.05).
Autonomic dysfunction occurs in all common dementias but is especially prominent in PDD with important treatment implications.
The autonomic nervous system (ANS) is activated in parallel with the motor system during cyclical and effortful imagined actions. However, it is not clear whether the ANS is activated during motor imagery of discrete movements and whether this activation is specific to the movement being imagined. Here, we explored these topics by studying the baroreflex control of the cardiovascular system.
Arterial pressure and heart rate were recorded in ten subjects who executed or imagined trunk or leg movements against gravity. Trunk and leg movements result in different physiological reactions (orthostatic hypotension phenomenon) when they are executed. Interestingly, ANS activation significantly, but similarly, increased during imagined trunk and leg movements. Furthermore, we did not observe any physiological modulation during a control mental-arithmetic task or during motor imagery of effortless movements (horizontal wrist displacements).
We concluded that ANS activation during motor imagery is general and not specific and physiologically prepares the organism for the upcoming effortful action.
Can stressful events in early life alter the response characteristics of the human stress axis? Individual differences in stress reactivity are considered potentially important in long-term health and disease, however little is known about the sources of these individual differences. We present evidence that adverse experience in childhood and adolescence can alter core components of the stress axis, including cortisol and heart rate reactivity.
We exposed 354 healthy young adults (196 women) to public speaking and mental arithmetic stressors in the laboratory. Stress responses were indexed by self-report, heart rate, and cortisol levels relative to measures on a nonstress control day. Subjects were grouped into those who had experienced 0, 1, or 2 or more significant adverse life events including Physical or Sexual Adversity (mugged, threatened with a weapon, experienced a break-in or robbery; or raped or sexually assaulted by a relative or nonrelative) or Emotional Adversity (separation from biological mother or father for at least 6 months prior to age 15).
Experience of adversity predicted smaller heart rate and cortisol responses to the stressors in a dose-dependent fashion (0 > 1 > 2 or more events; (Fs = 5.79 and 8.11, ps < .004) for both men and women. This was not explained by differences in socioeconomic status, the underlying cortisol diurnal cycle, or subjective experience during the stress procedure.
The results indicate a long-term impact of stressful life experience on the reactivity of the human stress axis.
gender; heart rate; cortisol; stress reactivity; lifetime adversity; mental stress
Background: Oral ingestion of water increases seated blood pressure in patients with chronic autonomic failure by mechanisms that remain unclear. As orthostatic hypotension is common in chronic autonomic failure, and is not always adequately controlled by medication, the potential benefits of water ingestion on standing blood pressure were studied in two types of autonomic failure: multiple system atrophy (MSA), in which the lesion is central and pre-ganglionic, and pure autonomic failure (PAF), in which the lesion is post-ganglionic.
Methods: In 14 patients with autonomic failure (seven PAF and seven MSA) standing blood pressure and heart rate were measured before, and 15 and 35 minutes after ingestion of 480 ml distilled water. Patients remained seated for 15 minutes after water ingestion, with beat to beat cardiovascular indices measured with the Portapres II device with subsequent Modelflow analysis.
Results: Standing prior to water ingestion caused a significant fall in blood pressure in all patients. After water ingestion there was a rise in seated blood pressure. Seated and standing blood pressure at 15 and 35 minutes after water ingestion was significantly higher than before water, with an improvement in orthostatic symptoms. The time to first significant rise in seated blood pressure occurred at 5 minutes post water ingestion in PAF and at 13 minutes in MSA. These increases were accompanied by increases in total peripheral resistance, reaching significance by 5 minutes in PAF and 13 minutes in MSA. There were no significant changes in cardiac output, stroke volume, or ejection fraction.
Conclusions: Water is thus beneficial in improving standing BP in AF, acting within 15 minutes in both MSA and PAF. The earlier onset of the pressor effect in PAF may reflect the differing lesion site and underlying pathophysiology between these conditions.
The purpose of this study was to investigate the temporal relationship between autonomic changes and pain activation in migraine and tension-type headache induced by stress in a model relevant for everyday office-work.
We measured pain, blood pressure (BP), heart rate (HR) and skin blood flow (BF) during and after controlled low-grade cognitive stress in 22 migraineurs during headache-free periods, 18 patients with tension-type headache (TTH) and 44 healthy controls. The stress lasted for one hour and was followed by 30 minutes of relaxation.
Cardiovascular responses to cognitive stress in migraine did not differ from those in control subjects. In TTH patients HR was maintained during stress, whereas it decreased for migraineurs and controls. A trend towards a delayed systolic BP response during stress was also observed in TTH. Finger BF recovery was delayed after stress and stress-induced pain was associated with less vasoconstriction in TTH during recovery.
It is hypothesized that TTH patients have different stress adaptive mechanisms than controls and migraineurs, involving delayed cardiovascular adaptation and reduced pain control system inhibition.
Background: Autonomic dysfunction has been described in primary Sjögren's syndrome (SS).
Objective: To investigate the circulatory autonomic regulation in patients with primary SS by power spectral analysis of heart rate and blood pressure variability.
Methods: Forty three (42 female) patients with primary SS, mean age 52 years (range 23–80), with a mean disease duration of eight years (range 1–30) and 30 (15 female) healthy controls, mean age 43 years (range 21–68) were studied. In each patient blood pressure, heart rate, and respiration were measured continuously during supine rest and orthostatic challenge (60° head-up tilt). Power spectral analysis was performed to determine possible differences in short term sympathetic and parasympathetic autonomic regulation between patients and controls. Furthermore, spectral parameters were studied in relation to illness severity and disease duration of the patients with primary SS.
Results: After controlling for differences in age, heart rate variability of the mid-frequency band and the variation coefficient of systolic blood pressure were significantly lower in patients with primary SS than in controls during supine rest. During 60° tilt patients with primary SS showed a significantly higher mean heart rate, mean systolic blood pressure, and variation coefficient of diastolic blood pressure, and a significantly lower baroreflex index than controls. After controlling for age, no differences were found either in heart rate variability, blood pressure results, and baroreflex sensitivity during supine rest and tilt between the subgroups divided according to disease duration, Schirmer test results, or between the subgroups with different fatigue scores. No differences were found in spectral data between the groups with and without positive antinuclear antibody serology.
Conclusion: For the group no differences in sympathetic and parasympathetic cardiac control were seen between patients with primary SS and controls, as assessed by spectral techniques, although some cardiovascular differences were found, particularly during orthostatic challenge.
To determine mRNA expression differences in genes involved in signaling and modulating sensory fatigue, and muscle pain in patients with Chronic Fatigue Syndrome (CFS) and Fibromyalgia Syndrome (FM) at baseline, and following moderate exercise.
Forty eight Patients with CFS-only, or CFS with comorbid FM, 18 Patients with FM that did not meet criteria for CFS, and 49 healthy Controls underwent moderate exercise (25 minutes at 70% maximum age predicted heart-rate). Visual-analogue measures of fatigue and pain were taken before, during, and after exercise. Blood samples were taken before, and 0.5, 8, 24, and 48 hours after exercise. Leukocytes were immediately isolated from blood, number coded for blind processing and analyses, and flash frozen. Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic, and immune functions was compared between groups at baseline, and following exercise. Changes in amounts of mRNA were correlated with behavioral measures, and functional clinical assessments.
No gene expression changes occurred following exercise in Controls. In 71% of CFS patients, moderate exercise increased most sensory and adrenergic receptor’s and one cytokine gene’s transcription for 48 hours. These post-exercise increases correlated with behavioral measures of fatigue and pain. In contrast, for the other 29% of CFS patients, adrenergic α-2A receptor’s transcription was decreased at all time points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM only patients showed no post-exercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than Controls.
At least two subgroups of CFS patients can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the CFS patients with orthostatic intolerance, showed no post-exercise increases in any gene, and was defined by decreases in mRNA for α-2A. FM only patients can be identified by baseline increases in 3 genes. Post-exercise increases for 4 genes meet published criteria as an objective biomarker for CFS, and could be useful in guiding treatment selection for different subgroups.
chronic fatigue syndrome; fatigue; orthostatic symptoms; autonomic dysfunction; gene expression; fibromyalgia
Objectives: To investigate differences between burnout patients and healthy controls regarding basal physiological values and physiological stress responses. Measures of the sympathetic-adrenergic-medullary (SAM) axis and the hypothalamic-pituitary-adrenal (HPA) axis were examined.
Methods: SAM axis and HPA axis activity was compared between 22 burnout patients and 23 healthy controls. SAM axis activity was measured by means of heart rate (HR) and blood pressure (BP). HPA axis activity was investigated by means of salivary cortisol levels. Resting levels of HR, BP, and cortisol were determined as well as reactivity and recovery of these measures during a laboratory session involving mental arithmetic and speech tasks. In addition, morning levels of cortisol were determined.
Results: Burnout patients showed higher resting HR than healthy controls. BP resting values did not differ between burnout patients and healthy controls, nor did cardiovascular reactivity and recovery measurements during the laboratory session. Basal cortisol levels and cortisol reactivity and recovery measures were similar for burnout patients and healthy controls. However, burnout patients showed elevated cortisol levels during the first hour after awakening in comparison to healthy controls.
Conclusions: The findings provided limited proof that SAM axis and HPA axis are disturbed among burnout patients. Elevated HR and elevated early morning cortisol levels may be indicative of sustained activation.
Chronic fatigue syndrome (CFS) is defined by debilitating fatigue that is exacerbated by physical or mental exertion. To search for markers of CFS-associated post-exertional fatigue, we measured peripheral blood gene expression profiles of women with CFS and matched controls before and after exercise challenge.
Women with CFS and healthy, age-matched, sedentary controls were exercised on a stationary bicycle at 70% of their predicted maximum workload. Blood was obtained before and after the challenge, total RNA was extracted from mononuclear cells, and signal intensity of the labeled cDNA hybridized to a 3800-gene oligonucleotide microarray was measured. We identified differences in gene expression among and between subject groups before and after exercise challenge and evaluated differences in terms of Gene Ontology categories.
Exercise-responsive genes differed between CFS patients and controls. These were in genes classified in chromatin and nucleosome assembly, cytoplasmic vesicles, membrane transport, and G protein-coupled receptor ontologies. Differences in ion transport and ion channel activity were evident at baseline and were exaggerated after exercise, as evidenced by greater numbers of differentially expressed genes in these molecular functions.
These results highlight the potential use of an exercise challenge combined with microarray gene expression analysis in identifying gene ontologies associated with CFS.
The aim of this study was to compare cardiovascular autonomic nervous system function in patients with primary Sjögren's syndrome (pSS) with that in control individuals, and to correlate the findings with autonomic symptoms and the presence of exocrine secretory dysfunction.
Twenty-seven female patients with pSS and 25 control individuals completed the COMPASS (Composite Autonomic Symptom Scale) self-reported autonomic symptom questionnaire. Beat-to-beat heart rate and blood pressure data in response to five standard cardiovascular reflex tests were digitally recorded using a noninvasive finger pressure cuff and heart rate variability was analyzed by Fourier spectral analysis. Analysis was performed by analysis of variance (ANOVA), multivariate ANOVA and repeated measures ANOVA, as indicated. Factor analysis was utilized to detect relationships between positive autonomic symptoms in pSS patients.
Multiple, mild autonomic disturbances were observed in pSS patients relating to decreased heart rate variability, decreased blood pressure variability and increased heart rate, which were most evident in response to postural change. There was a strong trend toward an association between decreased heart rate variability and increased severity of the secretomotor, orthostatic, bladder, gastroparesis and constipation self-reported autonomic symptom cluster identified in pSS patients. This symptom cluster was also associated with fatigue and reduced unstimulated salivary flow, and therefore may be an important component of the clinical spectrum of this disease.
There was evidence of mild autonomic dysfunction in pSS as measured with both cardiovascular reflex testing and self-reported symptoms. Pathogenic autoantibodies targeting M3 muscarinic receptors remain a strong candidate for the underlying pathophysiology, but practical assays for the detection of this autoantibody remain elusive.
OBJECTIVES--To investigate if autonomic nervous system function, reflected in cardiovascular variables, among patients with neck-shoulder symptoms (tension neck group (T)) differed from that in a symptom free control group (C), and to establish its relation with pain and psychological stress. METHODS--Twelve women with tension neck and nine controls in secretarial jobs were studied. They underwent an orthostatic test, deep breathing test, Valsalva manoeuvre, isometric handgrip test, and muscular endurance test. Pain was measured using visual analogue scales, and psychological stress by the Modified Somatic Perception Questionnaire (MSPQ). Plasma endothelin-1 (ET-1) was measured using high pressure liquid chromatography and radioimmunoassay. RESULTS--Signs of psychological stress were significantly (p < 0.001) more common in group T than in group C. Mean resting heart rate in group T (77.8 (SE 2.9) beats/min; range 64-100) was significantly greater than that in group C (63.8 (3.1) beats/min; range 52-80) (p < 0.01). In the orthostatic test, the overall changes in R-R intervals during the first 40 heart beats after standing up and during seven minutes of testing differed significantly between the groups (p < 0.001, < 0.05, respectively). The increase in diastolic blood pressure in the three minute isometric handgrip test was significantly less in group T (19.4 (3.5) mm Hg; range -5 to 35) than in group C (30 (3.4) mm Hg; range 15-50) (p < 0.05). The MSPQ score in the study group (n = 21) correlated positively with resting heart rate (r = 0.462, p < 0.05) and negatively with increase in diastolic blood pressure (r = -0.514, p < 0.05). Plasma concentrations of ET-1 did not differ between the groups. CONCLUSION--Increased sympathetic activity was found among patients having neck-shoulder symptoms. Local mechanisms may have influenced the cardiovascular changes observed during isometric testing in these patients.
CFS (chronic fatigue syndrome) is commonly co-morbid with POTS (postural tachycardia syndrome). Individuals with CFS/POTS experience unrelenting fatigue, tachycardia during orthostatic stress and ill-defined neurocognitive impairment, often described as ‘mental fog’. We hypothesized that orthostatic stress causes neurocognitive impairment in CFS/POTS related to decreased CBFV (cerebral blood flow velocity). A total of 16 CFS/POTS and 20 control subjects underwent graded tilt table testing (at 0, 15, 30, 45, 60 and 75°) with continuous cardiovascular, cerebrovascular, and respiratory monitoring and neurocognitive testing using an n-back task at each angle. The n-back task tests working memory, concentration, attention and information processing. The n-back task imposes increasing cognitive challenge with escalating (0-, 1-, 2-, 3- and 4-back) difficulty levels. Subject dropout due to orthostatic presyncope at each angle was similar between groups. There were no n-back accuracy or RT (reaction time) differences between groups while supine. CFS/POTS subjects responded less correctly during the n-back task test and had greater nRT (normalized RT) at 45, 60 and 75°. Furthermore, at 75° CFS/POTS subjects responded less correctly and had greater nRT than controls during the 2-, 3- and 4-back tests. Changes in CBFV were not different between the groups and were not associated with n-back task test scores. Thus we conclude that increasing orthostatic stress combined with a cognitive challenge impairs the neurocognitive abilities of working memory, accuracy and information processing in CFS/POTS, but that this is not related to changes in CBFV. Individuals with CFS/POTS should be aware that orthostatic stress may impair their neurocognitive abilities.
cerebral blood flow; chronic fatigue syndrome (CFS); graded tilt testing; neurocognition; orthostatic stress; postural tachycardia syndrome (POTS)
In healthy, noninjured, individuals, passive (i.e., nonexercising) whole-body heating has the potential to cause significant cardiovascular stress that may be second only to the cardiovascular stress associated with exercise. For example, such a heat stress can increase heart rate to well over 100 beats·min−1 with cardiac output increasing upward to 13 L·min−1. This increase in cardiac output is necessary to maintain blood pressure due to profound reductions in total vascular conductance associated with cutaneous vasodilation. These responses are accompanied with elevations in sympathetic activity and reductions in vascular conductance (i.e., increased vascular resistance) from noncutaneous beds. While heat-stressed, blood pressure control is compromised resulting in orthostatic intolerance. A plausible explanation for such an event is that heat stress impairs baroreflex responsiveness perhaps due to the reduced range by which baroreflexes can increase heart rate, cardiac output, sympathetic activity, and vascular resistance during a hypotensive challenge. Given that dynamic exercise has the potential to cause large increases in internal temperature, possibly a component of the response to exercise, with respect to baroreflex control of blood pressure, may be affected by the thermal load during the exercise bout. Within this context, the purpose of this review was to summarize findings investigating the effects of heat stress on baroreflex regulation of blood pressure.
HYPERTHERMIA; BARORECEPTORS; SYMPATHETIC NERVE ACTIVITY; HEART RATE; SKIN BLOOD FLOW