Marker Of Sympathetic Tone Research Articles

Heart rate variability in patients presenting with anginal symptoms in absence of cardiac and other diseases

Objectives: Angina is a symptom of coronary artery disease (CAD). Modulation of cardiac autonomic tone as assessed by heart rate (HR) variability (HRV) is found reduced in patients with CAD; myocardial ischemia, myocardial infarction and some other cardiovascular diseases. Reduced HRV has been found associated with sudden cardiac death in these CAD patients. Several patients present with anginal symptoms clinically in absence of CAD or other diseases. The status of HRV is not much clear in these patients. Thus, we aimed to assess HRV in patients with angina with and without myocardial ischemia and compare it with HRV of healthy subjects of similar age groups and follow-up patients for 1 year for cardiac/health events. Materials and Methods: The study included 61 consecutive male patients clinically presenting with angina and 30 healthy subjects. Based on Thallium-201 myocardial perfusion Single-photon emission computerized tomography (SPECT) imaging, patients were divided into two groups; patients with myocardial perfusion defects (MPD), (n = 33, age 54.91 ± 7.43 years) and patients with no MPD (NMPD), NMPD (n = 28, age 53.04 ± 8.50 years). Short-term HRV was assessed in all patients and subjects in resting supine position following standard protocol. All MPD and 25 NMPD patients could be followed up for 1 year for cardiac/health events. Results: Surprisingly, the NMPD patients showed significantly reduced HRV, Standard deviation of the N-N intervals, The square root of the mean squared differences of successive N-N intervals, Percentage of the number of interval differences of successive N-N intervals greater than >50 ms divided by total number of R-R intervals, low frequency (LF) power, High Frequency (HF) power and total power as compared to both MPD patients and healthy subjects. (Total power [NMPD vs. MPD]: 610.1 [379.9–1072.8] vs. 1508.0 [748.4–2339.4] millisecond squares (ms2), P = 0.001), healthy subjects (Total power: 1414.6 [1104.6-2141.5] ms2, P = 0.001). The markers of sympathetic tone; LF (normalised unit) and LF/HF ratio were higher in NMPD patients as compared to MPD patients resulting in an altered sympathovagal balance. During a 1-year follow-up, sudden death was seen in one MPD patient (3.1%) and two NMPD patients (8%). Conclusion: The NMPD patients showed significantly reduced HRV as compared to both MPD patients and Healthy subjects with an altered sympathovagal balance. Sudden death was also seen in NMPD patients as MPD patients.

Autonomic markers of extubation readiness in premature infants.

In premature infants, extubation failure is common and difficult to predict. Heart rate variability (HRV) is a marker of autonomic tone. Our aim is to test the hypothesis that autonomic impairment is associated with extubation readiness. Retrospective study of 89 infants <28 weeks. HRV metrics 24 h prior to extubation were compared for those with and without extubation success within 72 h. Receiver-operating curve analysis was conducted to determine the predictive ability of each metric, and a predictive model was created. Seventy-three percent were successfully extubated. The success group had significantly lower oxygen requirement, higher sympathetic HRV metrics, and a lower parasympathetic HRV metric. α1 (measure of autocorrelation, related to sympathetic tone) was the best predictor of success-area under the curve (AUC) of .73 (p = 0.001), and incorporated into a predictive model had an AUC of 0.81 (p < 0.0001)-sensitivity of 81% and specificity of 78%. Extubation success is associated with HRV. We show an autonomic imbalance with low sympathetic and elevated parasympathetic tone in those who failed. α1, a marker of sympathetic tone, was noted to be the best predictor of extubation success especially when incorporated into a clinical model. This article depicts autonomic markers predictive of extubation success. We depict an autonomic imbalance in those who fail extubation with heightened parasympathetic and blunted sympathetic signal. We describe a predictive model for extubation success with a sensitivity of 81% and specificity of 78%.

345 Blood pressure and autonomic function in essential hypertension: comparative evaluation of 24-hour heart rate variability and blood pressure

Abstract Aims Arterial hypertension (AHT) represents the leading cause of cardiovascular disease (CVD) and premature death worldwide. Essential AHT accounts for 95% of all cases of hypertension; although the aetiology of essential AHT is still largely unknown, a pivotal role of autonomic nervous system has been proposed and demonstrated. Both excessive sympathetic tone and vagal withdrawal, that define autonomic dysfunction, has been associated with essential AHT. The aim of our study was to investigate the relationship between blood pressure and autonomic function in essential hypertension; this was done comparing 24 h heart rate variability and 24 h blood pressure data, simultaneously collected, in a population of essential AHT subjects. Methods A prospective registry of 179 consecutive not selected essential AHT patients were considered in the present study. All patients underwent cardiac evaluation at the Primary and Secondary Cardiovascular Prevention Unit of the Don Gnocchi Foundation of Parma. All subjects underwent 24 h ECG monitoring, and 24 h Ambulatory Blood Pressure Monitoring, during the same day. Twenty-four hours Heart Rate variability analysis included: Time-domain, frequency-domain and non-linear domain. Results Mean age was 60 0a11.7 years, male gender was prevalent (68.4%). Among the population 26 (14.7%) subjects had diabetes; the prevalence of family history of CVD was 61.7% and 66.5% had dyslipidaemia; body mass index mean values were 27.6 7.4.3. In the whole population, the prevalence of uncontrolled AHT was 80.5%, divided into: 53.1% systo-diastolic, 17.9% isolated systolic, and 9.5% isolated diastolic. The prevalence of untreated AHT (recent diagnosis) was 40.2%, while treated AHT was 59.8% and only 19.6% had controlled blood pressure values (AHT at target). 12.3% of patients were treated with Beta Blockers. A significant correlations between diastolic blood pressure (DBP) values (24 h and day-time), LF/HF ratio (24 h) (r = 0.200; P = 007) and DFA alfa1 (24 h) (r = 0.325; P = 0.000), two know markers of sympathetic tone, were found. A higher sympathetic tone, expressed as high LF/HF, was found in isolated diastolic AHT compared to other types of AHT and the lowest sympathetic tone was found in isolated systolic AHT. Considering non-linear (complexity) analysis, DFA alfa1 (24 h) showed a significant correlation with DBP values that remained independent even after multiple adjustment for BMI, age, gender and Beta Blockers (β = 0.218; P = 0.011). Moreover, the lack of DBP control was associated with high sympathetic tone (LF/HF 3.8 112.3 vs 5.5 .33.3; P &amp;lt; 0.0001). On the other hand, no significant correlations between all DBP data and vagal markers, such as SDNN index, RMSSD and HF, were found. Again, no significant correlations between 24 h, daytime, night-time SBP and time or frequency HRV data as well as with non-linear (complexity) analysis were found. Finally, considering ‘autonomic dipping’, expressed as changes in HRV data between day and night, a strong inverse correlation between vagal markers and Heart Rate Dipping (r = −0.297; P &amp;lt; 0.0001) was found; correlation that remain independent even adjusted for age, gender, BMI, and BB. On the other hand, no association between blood pressure dipping and autonomic dipping was found. Conclusion Diastolic blood pressure and uncontrolled diastolic AHT, rather than systolic AHT, are associated with a hyper-sympathetic tone rather than with blunted vagal tone. The lack of heart rate dipping during night-time in AHT is associated with blunted vagal activation rather than a persistent night-time hyper-adrenergic tone.

One-year follow-up of blood viscosity factors and hematocrit/viscosity ratio inelite soccer players.

We investigated to what extent aprediction of the 'ideal' hematocrit based on individual hemorheological profile with an equation of viscosity is relevant in trained athletes, and how the agreement between theoretical and actual values is modified by changes in training volume and performance. Elite soccer players (national level: 18-32yr, weight 61-83 kg, body mass index 20.9-25.8 kg/m2) were seen twice at one year interval. Hemorheologic parameters were measured with the MT90 viscometer and the Myrenne aggregometer the theoretical bell-shaped curve of hematocrit/viscosity ratio as afunction of hematocrit was reconstructed with Quemada's equation using actual plasma viscosity and red cell rigidity to predict hematocrit/viscosity at various hematocrit levels. RBC aggregation is correlated at baseline with fat mass (M1 = 0.552 p < 0.02) and changes in aggregation are related to changes in fat mass (M = 0.652, p < 0.05; M1 = 0.647, p < 0.05). Predicted and actual hematocrit are correlated (r = 0.644, p < 0.05) but exhibit discrepancies (mean difference -1% range [3.24 to 1.24]) and those discrepancies are inversely correlated to the level of predicted hematocrit (r = -0.912, p < 0.01), to systolic blood pressure (r = -0.626, p < 0.05), and to the overtraining score (r = -0.693, p < 0.05). After one year changes in hematocrit are aclose reflect of the change in training volume (r = -0.877, p < 0.01) but are not correlated to fitness changes. Therefore in these athletes i) systemic hematocrit is close to its predicted 'ideal value", suggesting the accuracy of the prediction; ii) red cell aggregation is correlated to fat mass even in nonobese subjects; iii) hematocrit is lower than predicted by the model when markers of sympathetic tone (systolic blood pressure, overtraining score) are increased; iv) weekly training volume appears the main determinant of the reduction of hematocrit.

Highly sensitive index of sympathetic activity based on time-frequency spectral analysis of electrodermal activity.

Time-domain indices of electrodermal activity (EDA) have been used as a marker of sympathetic tone. However, they often show high variation between subjects and low consistency, which has precluded their general use as a marker of sympathetic tone. To examine whether power spectral density analysis of EDA can provide more consistent results, we recently performed a variety of sympathetic tone-evoking experiments (43). We found significant increase in the spectral power in the frequency range of 0.045 to 0.25 Hz when sympathetic tone-evoking stimuli were induced. The sympathetic tone assessed by the power spectral density of EDA was found to have lower variation and more sensitivity for certain, but not all, stimuli compared with the time-domain analysis of EDA. We surmise that this lack of sensitivity in certain sympathetic tone-inducing conditions with time-invariant spectral analysis of EDA may lie in its inability to characterize time-varying dynamics of the sympathetic tone. To overcome the disadvantages of time-domain and time-invariant power spectral indices of EDA, we developed a highly sensitive index of sympathetic tone, based on time-frequency analysis of EDA signals. Its efficacy was tested using experiments designed to elicit sympathetic dynamics. Twelve subjects underwent four tests known to elicit sympathetic tone arousal: cold pressor, tilt table, stand test, and the Stroop task. We hypothesize that a more sensitive measure of sympathetic control can be developed using time-varying spectral analysis. Variable frequency complex demodulation, a recently developed technique for time-frequency analysis, was used to obtain spectral amplitudes associated with EDA. We found that the time-varying spectral frequency band 0.08-0.24 Hz was most responsive to stimulation. Spectral power for frequencies higher than 0.24 Hz were determined to be not related to the sympathetic dynamics because they comprised less than 5% of the total power. The mean value of time-varying spectral amplitudes in the frequency band 0.08-0.24 Hz were used as the index of sympathetic tone, termed TVSymp. TVSymp was found to be overall the most sensitive to the stimuli, as evidenced by a low coefficient of variation (0.54), and higher consistency (intra-class correlation, 0.96) and sensitivity (Youden's index > 0.75), area under the receiver operating characteristic (ROC) curve (>0.8, accuracy > 0.88) compared with time-domain and time-invariant spectral indices, including heart rate variability.

Central Depletion of Brain-Derived Neurotrophic Factor in Mice Results in High Bone Mass and Metabolic Phenotype

Brain-derived neurotrophic factor (BDNF) plays important roles in neuronal differentiation/survival, the regulation of food intake, and the pathobiology of obesity and type 2 diabetes mellitus. BDNF and its receptor are expressed in osteoblasts and chondrocyte. BDNF in vitro has a positive effect on bone; whether central BDNF affects bone mass in vivo is not known. We therefore examined bone mass and energy use in brain-targeted BDNF conditional knockout mice (Bdnf(2lox/2lox)/93). The deletion of BDNF in the brain led to a metabolic phenotype characterized by hyperphagia, obesity, and increased abdominal white adipose tissue. Central BDNF deletion produces a marked skeletal phenotype characterized by increased femur length, elevated whole bone mineral density, and bone mineral content. The skeletal changes are developmentally regulated and appear concurrently with the metabolic phenotype, suggesting that the metabolic and skeletal actions of BDNF are linked. The increased bone development is evident in both the cortical and trabecular regions. Compared with control, Bdnf(2lox/2lox)/93 mice show greater trabecular bone volume (+50% for distal femur, P < 0.001; +35% for vertebral body, P < 0.001) and midfemoral cortical thickness (+11 to 17%, P < 0.05), measured at 3 and 6 months of age. The skeletal and metabolic phenotypes were gender dependent, with female being more affected than male mice. However, uncoupling protein-1 expression in brown fat, a marker of sympathetic tone, was not different between genotypes. We show that deletion of central BDNF expression in mice results in increased bone mass and white adipose tissue, with no significant changes in sympathetic signaling or peripheral serotonin, associated with hyperphagia, obesity, and leptin resistance.

Increased Visceral Adipose Tissue Is Associated With Increased Resting Heart Rate in Patients With Manifest Vascular Disease

Abdominal obesity is characterized by sympathetic nerve activation (SNA), probably mediated by elevated insulin and leptin levels. Resting heart rate (RHR) is a marker of sympathetic tone, and independently associated with cardiovascular events and death in various populations. We investigated and quantified the relation between visceral adipose tissue (VAT) and RHR in patients with vascular disease. In 3,723 patients with manifest vascular disease, visceral and subcutaneous fat tissue was measured with ultrasonography. RHR was obtained from an electrocardiogram (ECG). The association between quartiles of VAT and RHR was quantified using linear regression analysis with adjustments for potential confounding factors. Separate analyses were performed for men and women and for location of vascular disease. Visceral fat was categorized into sex-pooled quartiles (Q) ranging from 2.7-8.0 cm in Q1 (reference) to 9.4-20.6 cm in Q4. High visceral fat thickness was associated with increased RHR, in men (Q4 vs. Q1, β = 4.36; 95% confidence interval (CI) = 3.11-5.61) and women (β = 1.48; 95% CI = -0.70 to 3.66), after full adjustment. Waist circumference and BMI had a significant relation with RHR in men (β = 3.51; 95% CI = 2.21-4.81 and β = 2.80; 95% CI = 1.51-4.08, respectively) but these relations were smaller and not significant in women (β = 0.71; 95% CI = -1.44 to 2.85 and β = 0.24; 95% CI = -1.90 to 2.37, respectively). There was no relation between subcutaneous fat and RHR in men and women. The relation between visceral fat and RHR was similar in patients with different locations of vascular diseases. Increased visceral fat is associated with increased RHR in male and female patients with vascular disease, independent of the location.

Influence of resting energy expenditure on blood pressure is independent of body mass and a marker of sympathetic tone

Two recent examinations reported a strong association between blood pressure (BP) and resting energy expenditure (REE), independent of body mass and body composition. Both reports postulate that neurohumoral processes that contribute to variation in REE may partly mediate the body mass effect on BP. Therefore, we examined the relationship of REE and BP in 108 asymptomatic women ( a) to confirm previous findings in a novel population and ( b) to examine the impact of a marker of sympathetic tone on this relationship, as this was indicated as a potentially salient intermediary in previous reports. All testing was performed during a 4-day admission to the General Clinical Research Center. Resting energy expenditure was measured by indirect calorimetry, body composition was determined by dual-energy x-ray absorptiometry, and 24-hour fractionated urinary norepinephrine was determined by high-performance liquid chromatography. Multiple linear regression revealed REE as a significant predictor of systolic BP ( β = 0.30, P = .04), independent of race ( β = 0. 28, P = .01), age ( β = −0.02, P = .80), height ( β = −0.38, P = .08), fat mass ( β = 0.22, P = .20), fat-free mass ( β = 0.08, P = .65), and 24-hour fractionated urinary norepinephrine ( β = 0.06, P = .57); and the same model using diastolic BP as the dependent variable approached significance ( β = 0.24, P = .09). This study affirms previous findings that REE may be a potential mediator in resting BP, independent of many well-cited factors and, additionally, a marker of sympathetic tone.

A Protective Effect of Exercise Against Interpersonal Stress-Induced Cardiovascular Reactivity in Youth

Empirical evidence suggests an association between blood pressure reactivity to psychological stress in childhood and hypertension in adulthood. Acute aerobic exercise dampens blood pressure reactivity to subsequent stress in adults. PURPOSE: To determine if a single bout of interval exercise reduces cardiovascular reactivity to an interpersonal stressor in children. METHODS: Twenty-two children (n = 11 boys, n = 11 girls), ages 8-12 completed a control television-speech protocol and an experimental interval exercise-speech protocol. The order of test days was counterbalanced across children. Heart rate, blood pressure and perceived stress measures were collected at baseline, after watching television or exercising for 25 minutes (post-television or post-exercise), after reading for 20 minutes (post-read), and then after preparing (post-speech preparation) and giving a speech (post-speech). Salivary α-amylase concentrations were measured at baseline, post-speech preparation and post-speech as a marker of sympathetic tone. Children wore an accelerometer for 7 days to assess usual physical activity. RESULTS: Diastolic (DBP) and mean arterial pressures (MAP) increased (p < 0.001) when giving a speech on both the television and exercise days; however, the slope of the increase was greater (p < 0.006) when children watched television than when they exercised. Salivary α-amylase concentrations were lower (p < 0.05) when giving a speech after exercising than when giving a speech after watching television. The changes in DBP (ρ = 0.51, p < 0.02) and MAP (ρ = 0.44, p < 0.05) were correlated with the change in α-amylase from baseline to post-speech on the exercise day. CONCLUSIONS: An acute bout of interval exercise can attenuate stress-induced blood pressure responses and dampened sympathetic output may be one mechanism whereby exercise attenuates stress-induced cardiovascular reactivity. Frequent exercise may help to reduce the risk of hypertension and cardiovascular disease in adulthood by reducing stress-induced cardiovascular reactivity.

Heart rate as marker of sympathetic activity.

To determine the value of the supine heart rate as a marker of sympathetic tone by assessing, in a large group of subjects, the relationships between this parameter and two other indices of sympathetic activity, plasma norepinephrine and sympathetic nerve traffic. We studied 243 subjects aged 50.0+/-12.1 years (mean +/- SD). Of these, 38 were normotensive healthy controls, 113 subjects had untreated essential hypertension, 27 were obese normotensives and 65 had congestive heart failure. In each subject, over a 10 min supine period, we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), venous plasma norepinephrine (high-performance liquid chromatography) and efferent postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). In the whole study group, supine heart rate was correlated with both plasma norepinephrine (r = 0.32, P < 0.0001) and muscle sympathetic nerve activity (r = 0.38, P < 0.0001). This was also the case in the normotensive obese subjects and the heart failure subjects considered separately. Heart rate values were greater in the obese and the heart failure patients than in controls (75.1+/-13.0 and 78.2+/-13.0 versus 69.2+/-11.6 beats/min; P < 0.05 and P < 0.001, respectively), as were plasma norepinephrine (362.7+/-202 and 400.3+/-217 versus 230.4+/-126 pg/ml; P < 0.01 and P < 0.001, respectively) and muscle sympathetic nerve activity (44.1+/-14.7 and 55.3+/-14.3 versus 27.8+/-11.0 bursts/min; P < 0.001 for both). In contrast, in the essential hypertensive subjects, no significant relationship was found between these three indices of sympathetic activity. Furthermore, in the hypertensives, the heart rate was not increased, at variance with the sympathetic nerve traffic, which was greater than in controls (36.2+/-10.0 versus 27.8+/-11.0 bursts/min, P < 0.001). These data suggest that the supine heart rate can be regarded as a marker of intersubject differences in sympathetic tone, and that this is the case both in the general population and in those with cardiovascular diseases. Its value for this purpose is limited, however, and the limitations may be more evident in essential hypertension than in conditions such as obesity and heart failure.

New markers for type A behavior: pupil size and platelet epinephrine.

This study tested the hypothesis that the Type A behavior pattern and its components are associated with increased activity of the sympathetic nervous system. To do this, we employed two new markers of sympathetic tone--pupil size and platelet catecholamine content. Thirty-three healthy males were blindly rated for Type A behavior and verbal stylistic components by Structured Interview. Adrenergic tone to the pupils was assessed from pupil diameter recorded by infrared television pupillometry, and pupil alpha-adrenergic sensitivity was estimated from mydriatic response to ophthalmic phenylephrine. Platelet epinephrine and norepinephrine contents were assayed because these levels are associated with chronic, long-term circulating catecholamine levels. The results showed Type As had consistently larger pupil diameters than Type Bs (p = 0.03, 0.03, and 0.01). There was no difference in pupillary response to phenylephrine instillation between groups. Platelet epinephrine content was greater in Type A subjects (chi 2 = 4.25, p less than 0.04, t = 1.6, p = 0.06). Only the component of explosiveness was modestly associated with resting pupil size, and no components significantly predicted platelet catecholamines. We conclude that the results of these two new markers of autonomic activity, namely, pupil size and platelet epinephrine, suggest that Type A behavior is characterized by increased sympathetic nervous system tone although we cannot rule out the possibility of decreased activity of the parasympathetic nervous system.