Cardiovascular Autonomic Nervous System Function Research Articles

The Association of Measures of Cardiovascular Autonomic Function, Heart Rate, and Orthostatic Hypotension With Incident Glucose Disorders: The Cardiovascular Health Study.

The autonomic nervous system (ANS) innervates pancreatic endocrine cells, muscle, and liver, all of which participate in glucose metabolism. We tested whether measures of cardiovascular ANS function are independently associated with incident diabetes and annual change in fasting glucose (FG) levels as well as with insulin secretion and insulin sensitivity in older adults without diabetes. Heart rate (HR) and measures of HR variability (HRV) were derived from 24-h electrocardiographic monitoring. Blood pressure, seated and standing, was measured. Cox proportional hazards models and linear mixed models were used to analyze the associations between HRV, HR, and orthostatic hypotension (SBP >20 mmHg decline) and incident diabetes or longitudinal FG change. The mean annual unadjusted FG change was 1 mg/dL. Higher detrended fluctuation analyses (DFA) values, averaged over 4-11 (DFA1) or 12-20 beats (DFA2)-reflecting greater versus less organization of beat-to-beat intervals-were associated with less FG increase over time (per 1-SD increment: DFA1: -0.49 mg/dL/year [-0.96, -0.03]; DFA2: -0.55 mg/dL/year [-1.02, -0.09]). In mutually adjusted analyses, higher SD of the N-N interval (SDNN) was associated with less FG increase over time (per 1-SD increment: SDNN: -0.62 mg/dL/year [-1.22, -0.03]). Higher values of DFA1, DFA2, and SDNN were each associated with greater insulin secretion and insulin sensitivity but not with incident diabetes. We observed no association of HR or orthostatic hypotension with diabetes or FG change. Specific measures of cardiac autonomic function are prospectively related to FG level changes and insulin secretion and action.

Vitamin D Deficiency and Vasovagal Syncope in Children and Adolescents.

Aims: To investigate the association of vitamin D deficiency with cardiovascular autonomic nervous system function in children and adolescents with vasovagal syncope (VVS).Methods: This study recruited 76 pediatric patients with VVS and 15 healthy children. The 25-hydroxyvitamin D levels in serum among the participants were evaluated. Heart rate variability analysis including SDNN, rMSSD, and SDANN was tested in patients with VVS. The correlation between indices of time-domain analysis and serum vitamin D status of the children with VVS was investigated.Results: In this work, 25-hydroxyvitamin D levels in serum among VVS cases remarkably decreased compared with those among healthy controls (48.76 ± 19.25 vs. 67.62 ± 15.46 nmol/L, p < 0.01). The vitamin D deficient patients with VVS exhibited a lower rMSDD value compared to the non-deficient group with VVS (45.56 ± 16.87 vs. 61.90 ± 20.38 ms, p < 0.001, respectively). Pearson correlation analysis indicated that serum 25-hydroxyvitamin D levels had positive correlation with rMSDD values (r = 0.466, p < 0.001).Conclusions: As suggested by our data, VVS children and adolescents with vitamin D deficiency may have cardiac autonomic dysfunction and cardiac vagal tone decreases with the reduction in vitamin D level.

Spectral Analysis of Heart Rate Variability During Trigger-Point Acupuncture of Various Muscles.

Objective: The aim of this research was to clarify changes in cardiovascular autonomic nervous system function due to trigger-point (TP) acupuncture; the current author evaluated differences in responses among acupuncture at TPs of various muscles using spectral analysis of heart rate variability. Materials and Methods: Subjects were 48 healthy men. Before measurements began, subjects were assigned to a TP acupuncture or control group based on presence/absence of referred pain on applying pressure to a taut band within the right extensor digitorum muscle, tibialis anterior muscle, gluteus medius muscle, or masseter muscle. Measurements were conducted in a room with a temperature of 25°C, with subjects in a long sitting position after 10 minutes of rest. Acupuncture needles were retained for 10 minutes at 1 site on the right extensor digitorum muscle, tibialis anterior muscle, gluteus medius muscle, or masseter muscle. Electrocardiography was performed simultaneously with respiratory-cycle measurements. Based on the R-R interval on the electrocardiograms, frequency analysis was performed, low-frequency (LF) and high-frequency (HF) components were extracted, and the ratio of LF to HF components (LF/HF) was evaluated. Results: All subjects in the TP acupuncture group showed a transient increase in the HF component, but no significant changes in heart rate (HR) or LF/HF. In the control group, no significant changes were observed in HR, HF component, or LF/HF. Conclusions: These data suggest that acupuncture stimulation of TPs of the right extensor digitorum muscle, tibialis anterior muscle, gluteus medius muscle, and masseter muscle increases parasympathetic nerve activity transiently.

Reliability of pulse waveform separation analysis responses to an orthostatic challenge.

Cardiovascular autonomic nervous system function can be assessed using an orthostatic challenge to induce arterial wave reflection. While arterial reflection is typically estimated using a central augmentation index, a superior estimation can be obtained using pulse wave separation analysis to estimate the aortic backward pressure wave (Pb). However, to be of value in a clinical or research setting, an assessment tool must be precise (reliable). Therefore, this study sought to determine the measurement precision of Pb responses to a modified tilt-table test. Twenty healthy adults (26.4 year (SD 5.2), 24.7 kg/m2 (SD 3.8), 55% female) were tested in a fasted state on three different mornings separated by a maximum of seven days. Pressure waveforms were recorded on the left arm, and aortic waveforms were generated using a generalized transfer function. Subsequently, a physiologic flow waveform was assumed to separate the aortic pressure wave into its forward and timing-independent backward (Pb) components. The criterion intra-class correlation coefficient of ≥0.75 was exceeded at baseline (0.79), following a 5-min tilt (0.75), and following a 5-min recovery from tilt (0.75). The standard error of measurement was 7%. These findings indicate that in a healthy cohort, the Pb response to an orthostatic challenge can be assessed with acceptable precision. The next step is to determine the sensitivity (validity) of this technique in identifying cardiovascular autonomic dysfunction in patient groups.

Reliability of Pulse Waveform Separation Analysis Responses to an Orthostatic Challenge

PURPOSE: Cardiovascular autonomic nervous system function can be assessed by recording arterial wave reflection responses to an orthostatic challenge. Using pulse wave analysis, arterial wave reflection can be estimated using pulse wave separation analysis, whereby a triangular or a physiologic flow waveform is assumed and the aortic wave is separated into its forward and timing-independent reflected (Pb) components. This study sought to determine the measurement precision (between-day reliability) of Pb responses to an modified tilt-table test. METHODS: Twenty healthy adults (26.4 y (SD 5.2), 55% F, 24.7 kg/m2 (SD 3.8)) were tested on three different mornings in the fasted state, separated by a maximum of seven days. Oscillometric pressure waveforms were recorded on the left upper arm, and aortic waveforms were generated using a generalized transfer function. The criterion for acceptable reliability was an intra-class correlation coefficient (ICC) of 0.75. To express the percentage change that must occur at a group and individual level, the standard error of measurement (%SEM) and smallest detectable change (%SDC) were calculated. RESULTS: The criterion ICC (0.75) was exceeded at baseline (0.79), following 5 min tilt (0.75), and following 5 min recovery from tilt (0.75). The %SEM and %SDC for the 5 min tilt response were 7% and 19%, respectively. CONCLUSION: Arterial wave reflection responses to an orthostatic challenge can be assessed with acceptable between-day reliability using oscillometric pulse wave analysis.

47. Autonomic dysfunction in ALS patients: An early phase study_preliminary data

Amyotrophic Lateral Sclerosis (ALS) is a fatal degenerative motoneuron disease. Since 40 years, study investigating a possible Autonomic Nervous System (ANS) involvement are reported. Although results are contradictory and studies difficult to compare, ALS appears not to be a single disease entity, but a spectrum of disorders involving mainly, but not only, motoneurons. The aim of the study was to investigate cardiovascular ANS function in ALS patients with low disability and normal respiratory function. We have included patients diagnosed with ALS according to El Escorial criteria, able to walk unaided. We excluded patients with swallowing difficulties, affected by autonomic dysfunction of other origin and taking ANS influencing drugs. We also excluded patients with respiratory insufficiency. Patients underwent cholinergic and adrenergic evaluations: SSR and standard autonomic tests during continuous monitoring of heart rate and blood pressure. We evaluated HRV, BRS and spectral analysis of HF and LF of RRI and BP. We compared patients with matched normal controls. We did not find any significant difference between groups, indicating a tendency toward a normal function of ANS in early phase of disease. We will expand our sample and possibily try a genotipic–phenotipic correlation, given the heterogeneity of ALS spectrum.

Genetic, Epigenetic, and Environmental Factors Influencing Neurovisceral Integration of Cardiovascular Modulation: Focus on Multiple Sclerosis.

Thought to be an autoimmune inflammatory CNS disease, multiple sclerosis (MS) involves multiple pathologies with heterogeneous clinical presentations. An impaired neurovisceral integration of cardiovascular modulation, indicated by sympathetic and parasympathetic autonomic nervous system (ANS) dysfunction, is among common MS clinical presentations. ANS dysfunction could not only enhance MS inflammatory and neurodegenerative processes, but can also lead toclinical symptoms such as depression, fatigue, sleep disorder, migraine, osteoporosis,and cerebral hemodynamic impairments. Therefore, factors influencing ANS functional activities, in one way or another, will have a significant impact on MS disease course. This review describes the genetic and epigenetic factors, and their interactions with a number of environmental factors contributing to the neurovisceral integration of cardiovascular modulation, with a focus on MS. Future studies should investigate the improvement in cardiovascular ANS function, as a strategy for preventing and minimizing MS-related morbidities, and improving patients' quality of life.

Spectral Analysis of Heart Rate Variability during Trigger Point Acupuncture

To clarify changes in the cardiovascular autonomic nervous system function due to trigger point acupuncture, we evaluated differences in responses between acupuncture at trigger points and those at other sites using spectral analysis of heart rate variability. Subjects were 35 healthy men. Before measurements began the subjects were assigned to a trigger point acupuncture or control group based on the presence/absence of referred pain on applying pressure to a taut band within the right tibialis anterior muscle. The measurements were conducted in a room with a temperature of 25°C, with subjects in a long sitting position after 10 min rest. Acupuncture needles were retained for 10 min at two sites on the right tibialis anterior muscle. ECG was performed simultaneously with measurements of blood pressure and the respiratory cycle. Based on the R-R interval on the ECG, frequency analysis was performed, low-frequency (LF) and high-frequency (HF) components were extracted and the ratio of LF to HF components (LF/HF) was evaluated. The trigger point acupuncture group showed a transient decrease in heart rate and an increase in the HF component but no significant changes in LF/HF. In the control group, no significant changes were observed in heart rate, the HF component or LF/HF. There were no consistent changes in systolic or diastolic blood pressure in either group. These data suggest that acupuncture stimulation of trigger points of the tibialis anterior muscle transiently increases parasympathetic nerve activity.

Autonomic modulation in gestational diabetes mellitus

AimsThe aim of this study was to evaluate the influence of gestational diabetes mellitus (GDM) and positional aortocaval compression on cardiovascular autonomic nervous system (ANS) function in late pregnancy. MethodsPregnant women with (n=31) and without (n=12) GDM were evaluated at 30–35weeks gestation and 2–3months postpartum. Measures of ANS function included power spectral analysis (performed sitting) and RR-variation during deep breathing (performed supine). Time-related changes (late pregnancy versus 2–3months postpartum) for measurements of cardiovascular ANS function were analyzed using multivariate analysis of variance for repeated measures. ResultsBaseline characteristics were similar for both groups. Comparing ANS measures for GDM+versus GDM− women during pregnancy and postpartum revealed no significant differences. Time related changes indicated that during late pregnancy total spectral power, low frequency (LF) power, high frequency (HF) power, and RR-variation during deep breathing were significantly reduced (p<0.001 for all). The LF/HF ratio, however, was not significantly affected during late pregnancy (p=0.678). ConclusionsOur results suggest decreased activity in both branches of the ANS during mid-third trimester pregnancy, but no significant change in sympathovagal balance. Aortocaval compression appears to affect ANS function whether tests were performed sitting or supine for GDM+and GDM− women.

A study on analysis of Heart Rate Variability in hypertensive individuals

Introduction: Hypertension is a major risk factor for coronary artery disease, stroke and heart failure. Autonomic nervous system (ANS) dysfunction is an important factor in the development and progression of hypertension. Heart rate variability (HRV) is a simple, sensitive and non-invasive tool to monitor the cardiovascular ANS function. Thus, the present study was chosen as a simple tool to assess the sympathovagal balance by analysing the HRV changes in hypertensive individuals. Aims and Objectives: To analyse Heart Rate Variability (HRV) in hypertensive individuals. Materials and Methods: The study was conducted on 30 normotensive and 30 hypertensive subjects (BP≥140/90 mm Hg, according to JNC-7 classification). Lead-II ECG was recorded using the instrument PHYSIOPAC-PP4, MEDICAID system, Chandigarh and HRV analysis was done using Kubios HRV analyser. Spectral indices of HRV such as total power (TP), normalized low frequency power (LFnu), normalized high frequency power (HFnu), ratio of low frequency power to high frequency power (LF-HF ratio), standard deviation of normal-to-normal RR intervals (SDNN), root mean square successive difference (rMSSD) and the proportion of NN50 to the total number of NN intervals (pNN50) were assessed. Results: Our results showed significantly reduced HFnu (p 0.05), SDNN (p 0.05), rMSSD (p 0.05) and pNN50 (p 0.05) in hypertensive individuals. LFnu and LF-HF ratio was significantly increased (p 0.05) in hypertensive individuals.

Monitoring changes in heart rate, as an indicator of the cardiovascular autonomic nervous function, among patients at the sub-acute phase post-brain damage during a physiotherapy session: A preliminary investigation

Objectives: To assess cardiovascular autonomic nervous system function of patients post-brain-injury in the sub-acute phase during a physiotherapy session (PTS).Participants: Fourteen patients post-ischaemic stroke and 11 post-severe traumatic brain injuries.Intervention: Continuous electrocardiogram recording at rest, during active cycling and during routine PTS.Main outcome measure: Heart rate (HR) and Heart rate variability (HRV) parameters included the standard deviation of all R-R intervals (SDNN), the square root of the mean squared differences of successive differences (RMSSD), the Low-frequency (LF) power, High-frequency (HF) power and the LF/HF ratio.Results: The median HR at rest was 76 bpm (interquartile range 61–81). Significant increments were noted during activities; median HR during cycling was 93 bpm, during the most intense activity 91 bpm (p-value < 0.001). A significant decline in HRV parameters’ median values during cycling and PTS was observed only among patients post-stroke.Conclusions: Among patients post-brain injury, HR increased significantly during PTS in different activities and varied positions; therefore, therapists should be aware and monitor HR frequently during training. In addition, HRV values were low at rest and did not respond to activity among patients post-TBI, compared with higher values at rest and some response among patients post-stroke. This may indicate that autonomic impairment post-brain insult is more likely a consequence of central nervous system damage and less likely a result of pre-event cardiovascular illness.

Cardiovascular Autonomic Nervous System Function and Aerobic Capacity in Type 1 Diabetes

Impaired cardiovascular autonomic nervous system (ANS) function has been reported in type 1 diabetes (T1D) patients. ANS function, evaluated by heart rate variability (HRV), systolic blood pressure variability (SBPV), and baroreflex sensitivity (BRS), has been linked to aerobic capacity (VO2peak) in healthy subjects, but this relationship is unknown in T1D. We examined cardiovascular ANS function at rest and during function tests, and its relations to VO2peak in T1D individuals. Ten T1D patients (34 ± 7 years) and 11 healthy control (CON; 31 ± 6 years) age and leisure-time physical activity-matched men were studied. ANS function was recorded at rest and during active standing and handgrip. Determination of VO2peak was obtained with a graded cycle ergometer test. During ANS recordings SBPV, BRS, and resting HRV did not differ between groups, but alpha1 responses to maneuvers in detrended fluctuation analyses were smaller in T1D (active standing; 32%, handgrip; 20%, medians) than in CON (active standing; 71%, handgrip; 54%, p < 0.05). VO2peak was lower in T1D (36 ± 4 ml kg−1 min−1) than in CON (45 ± 9 ml kg−1 min−1, p < 0.05). Resting HRV measures, RMSSD, HF, and SD1 correlated with VO2peak in CON (p < 0.05) and when analyzing groups together. These results suggest that T1D had lower VO2peak, weaker HRV response to maneuvers, but not impaired cardiovascular ANS function at rest compared with CON. Resting parasympathetic cardiac activity correlated with VO2peak in CON but not in T1D. Detrended fluctuation analysis could be a sensitive detector of changes in cardiac ANS function in T1D.

Impaired cardiovascular autonomic nervous system function in patients with Churg–Strauss syndrome

Objectives: Although peripheral nervous system involvement in patients with Churg–Strauss syndrome (CSS) has been described, little is known about its autonomic part. Autonomic nervous system (ANS) function can be assessed by studying heart rate variability (HRV) and a decrease in the spectrum of HRV correlates with ANS impairment.Methods: Out of 24 CSS patients we chose 12 (four males, eight females, aged 40 ± 8.3 years) in disease remission and without cardiac involvement. Twelve age- and sex-matched healthy volunteers served as a control group. All underwent 24-h electrocardiogram (ECG) Holter recordings. HRV was calculated from 1-h segments, including: total power (TP), ultra-low frequency (ULF), very low frequency (VLF), low frequency (LF), and high frequency (HF) powers as well as normalized LF (LF%) and HF (HF%) powers and the LF to HF power ratio (LF/HF).Results: The CSS patients showed decreased HRV parameters in the 1-h domains: TP (2038 vs. 3622 ms2, p = 0.001), HF (561 vs. 1574 ms2, p < 0.001), LF (672 vs. 1050 ms2, p < 0.01), and VLF (544 vs. 738 ms2, p = 0.016). However, LF% and LF/HF ratio were markedly higher in CSS patients than in controls (53.4% vs. 39%, p < 0.001 and 1.1 vs. 0.64, p < 0.001), whereas HF% was lower in CSS than in controls (46.6% vs. 61%, p < 0.001). These results were independent of duration of the disease, eosinophil count, corticosteroids, or peripheral nerve involvement in the past.Conclusions: The CSS patients show impaired HRV parameters, indicating parasympathetic ANS dysfunction in addition to peripheral nervous system involvement.

Mild autonomic dysfunction in primary Sjögren's syndrome: a controlled study

IntroductionThe 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.MethodsTwenty-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.ResultsMultiple, 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.ConclusionThere 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.

Dysfunctional baroreflex regulation of sympathetic nerve activity in remitted patients with panic disorder

Many researchers have studied the abnormalities of autonomic nervous system (ANS) such as decreased heart rate variability, which is a risk factor for sudden cardiac death, in patients with panic disorder (PD). However, no consistent abnormality has been uncovered to date. One of the reasons for this controversy may be due to the fact that most of these conventional studies have analyzed each physiological variable independent of other indices. We examined the ANS in PD patients using a new method which can more directly investigate the function of the baroreflex by examining the relation between the blood pressure (BP) and heart rate (HR). During rest and audiovisual stimulation (AS) as mental stress such as being exposed to video imaginary of experiences such as driving motor vehicles, cardiovascular parameters, HR and BP were consecutively measured in 13 remitted PD patients and twenty aged and gender-matched normal controls (NC). In this study, to assess the cardiovascular ANS function (baroreflex) in PD we used the power spectrum analysis as usual and the mean of lag time (tau) between the Mayer wave components, which was closely related to sympathetic nerve activity of vasomotor, of HR and BP variability as a new trial. The PD patients and NC did not differ with regard to the power spectrum analysis of the heart rate. We found that tau in the PD group was significantly shorter than that in the NC both before and after AS, especially before. These findings suggest that remitted PD patients may have a dysfunctional baroreflex regulation of sympathetic nerve activity.

The Evaluation of Autonomic Nervous Function in a Patient with Hereditary Sensory and Autonomic Neuropathy Type IV with Novel Mutations of theTRKAGene

We report on a 10-year-old girl with anhidrosis and insensibility to pain, but no severe mental retardation or self-mutilation, diagnosed as hereditary sensory and autonomic neuropathy type IV (HSAN IV). Genetic analysis of her TRKA gene, which is responsible for HSAN IV, revealed two novel missense mutations in the tyrosine kinase domain. Cardiovascular autonomic nervous system function tests showed normal muscle sympathetic nerve activity associated with arterial baroreflex, reduced skin sympathetic nerve activity in the second and fifth fingers and palms, and abnormal circadian rhythm of cardiovascular autonomic nervous system. These findings have never before been reported in HSAN IV and may provide a clue to the neurological pathophysiology of this disease.

Effects of an ACE Inhibitor and a Calcium Channel Blocker on Cardiovascular Autonomic Nervous System and Carotid Distensibility in Patients with Mild to Moderate Hypertension

We investigated the relationship between cardiovascular autonomic nervous system function and carotid arterial distensibility during treatment with an angiotensin converting enzyme inhibitor (derapril) or a calcium channel blocker (manidipine) for hypertension. In 37 patients with hypertension, autonomic function was assessed by heart rate variability and baroreceptor sensitivity using phenylephrine injection. Left ventricular mass index and carotid arterial distensibility were assessed by ultrasound examinations. Before the medication, both baroreceptor sensitivity and heart rate variability correlated with carotid arterial distensibility, but not with left ventricular mass index by multiple regression analysis. Subsequently, patients were randomly allocated into two groups, derapril (n = 18) and manidipine (n = 19) for 20 weeks. At the end of the study, the change in baroreceptor sensitivity correlated with change in carotid arterial distensibility (r = 0.41, P < .05), but not with change in left ventricular mass index. Although derapril and manidipine decreased blood pressure and left ventricular mass index to the same extent, the former improved heart rate variability, baroreceptor sensitivity (5.0 ± 1.9 → 5.6 ± 2.0 msec/mm Hg), and carotid arterial distensibility (2.1 ± 0.8 → 2.5 ± 1.0 %kPa), but the latter did not improve them at all. Thus, impairment of the autonomic balance was related to the impairment of carotid arterial distensibility in hypertension; derapril, but not manidipine, significantly improved these abnormalities.