Burst Incidence Research Articles

Augmented Cardiopulmonary Baroreflex Sensitivity in Intradialytic Hypertension

IntroductionEnd-stage renal disease (ESRD) patients with a paradoxical increase in blood pressure (BP) during hemodialysis (HD), termed intradialytic hypertension (ID-HTN), are at significantly increased risk for mortality and adverse cardiovascular events. ID-HTN affects up to 15% of all HD patients, and the pathophysiologic mechanisms remain unknown. We hypothesized that ESRD patients prone to ID-HTN have heightened volume-sensitive cardiopulmonary baroreflex sensitivity (BRS) that leads to exaggerated increases in sympathetic nervous system (SNS) activation during HD.MethodsWe studied ESRD patients on maintenance HD with ID-HTN (n = 10) and without ID-HTN (controls, n = 12) on an interdialytic day, 24 to 30 hours after their last HD session. We measured continuous muscle sympathetic nerve activity (MSNA), beat-to-beat arterial BP, and electrocardiography (ECG) at baseline, and during graded lower body negative pressure (LBNP). Low-dose LBNP isolates cardiopulmonary BRS, whereas higher doses allow assessment of physiologic responses to orthostatic stress.ResultsThe ID-HTN patients had significantly higher pre- and post-HD BP, and greater interdialytic fluid weight gain compared to controls. There was a significantly greater increase in MSNA burst incidence (P = 0.044) during graded LBNP in the ID-HTN group, suggesting heightened cardiopulmonary BRS. The ID-HTN group also had a trend toward increased diastolic BP response during LBNP, and had significantly greater increases in BP during the cold pressor test.ConclusionPatients with ID-HTN have augmented cardiopulmonary BRS that may contribute to increased SNS activation and BP response during HD.

Microneurographic characterization of sympathetic responses during 1-leg exercise in young and middle-aged humans.

Muscle sympathetic nerve activity (MSNA) at rest increases with age. However, the influence of age on MSNA recorded during dynamic leg exercise is unknown. We tested the hypothesis that aging attenuates the sympatho-inhibitory response observed in young subjects performing mild to moderate 1-leg cycling. After predetermining peak oxygen uptake, we compared contra-lateral fibular nerve MSNA during 2 min each of mild (unloaded) and moderate (30%-40% of the work rate at peak oxygen uptake, halved for single leg) 1-leg cycling in 18 young (age, 23 ± 1 years (mean ± SE)) and 18 middle-aged (age, 57 ± 2 years) sex-matched healthy subjects. Mean height, weight, resting heart rate, systolic blood pressure, and percent predicted peak oxygen uptake were similar between groups. Middle-aged subjects had higher resting MSNA burst frequency and incidence (P < 0.001) and diastolic blood pressure (P = 0.04). During moderate 1-leg cycling, older subjects' systolic blood pressure increased more (+21 ± 5 vs. +10 ± 1 mm Hg; P = 0.02) and their fall in MSNA burst incidence was amplified (-19 ± 2 vs. -11 ± 2 bursts/100 heart beats; P = 0.01) but because heart rate rose less (+15 ± 3 vs. +19 ± 2 bpm; P = 0.03), exercise induced similar reductions in burst frequency (P = 0.25). Contrary to our initial hypothesis, with advancing age, mild- to moderate-intensity dynamic leg exercise elicits a greater rise in systolic blood pressure and a larger fall in MSNA.

A fuzzy comprehensive evaluation methodology for rock burst forecasting using microseismic monitoring

Rock bursts have become one of the most severe risks in underground coal mining and its forecasting is an important component in the safety management. Subsurface microseismic (MS) monitoring is considered potentially as a powerful tool for rock burst forecasting. In this study, a methodology for rock burst forecasting involving the use of a fuzzy comprehensive evaluation model was developed, which allows for a more quantitative evaluation of the likelihood for the occurrence of a rock burst incident. In the fuzzy model, the membership function was built using Gaussian shape combined with the exponential distribution function from the reliability theory. The weight of each index was determined utilising the performance metric F score from the confusion matrix. The comprehensive forecasting result was obtained by integrating the maximum membership degree principle (MMDP) and the variable fuzzy pattern recognition (VFPR). This methodology has been applied to a coal mine in China to forecast rock bursts. To select MS indices for rock burst forecasting using the fuzzy evaluation model, laboratory acoustic emission (AE) measurements of coal samples collected from the mine were performed. The model parameters were first calibrated using historical MS data over a period of four months, during which six rock burst incidents were observed. This calibrated model was able to forecast the occurrence of a subsequent rock burst incident in the mine.

Beta burst coupling across the motor circuit in Parkinson's disease

Exaggerated activity in the beta band (13–35 Hz) is a hallmark of basal ganglia signals in patients with Parkinson's disease (PD). Beta activity however is not constantly elevated, but comes in bursts. In previous work we showed that the longer beta bursts are maintained, the more the oscillatory synchronisation within the subthalamic nucleus (STN) increases, which is posited to limit the information coding capacity of local circuits. Accordingly, a higher incidence of longer bursts correlates positively with clinical impairment, while the opposite is true for short, more physiological bursts. Here, we test the hypothesis that beta bursts not only indicate local synchronisation within the STN, but also phasic coupling across the motor network and hence entail an even greater restriction of information coding capacity in patients with PD. Local field potentials from the subthalamic nucleus and EEG over the motor cortex area were recorded in nine PD patients after temporary lead externalization after surgery for deep brain stimulation and overnight withdrawal of levodopa. Beta bursts were defined as periods exceeding the 75th percentile of signal amplitude and the coupling between bursts was considered using two distinct measurements, first the % overlapping (%OVL) as a feature of the amplitude coupling and secondly the phase synchrony index (PSI) to measure the phase coupling between regions. %OVL between STN and cortex and between the left and the right STN was higher than expected between the regions than if they had been independent. Similarly, PSI was higher during bursts as opposed to non-bursts periods. In addition, %OVL was greater for long compared to short bursts. Our results support the hypothesis that beta bursts involve long-range coupling between structures in the basal ganglia-cortical network. The impact of this is greater during long as opposed to short duration beta bursts. Accordingly, we posit that episodes of simultaneously elevated coupling across multiple structures in the basal ganglia-cortical circuit further limit information coding capacity and may have further impact upon motor impairment.

The Stability and Repeatability of Spontaneous Sympathetic Baroreflex Sensitivity in Healthy Young Individuals.

Spontaneous sympathetic baroreflex sensitivity (BRS) is a valuable tool for assessing how well the baroreflex buffers beat-to-beat changes in blood pressure. However, there has yet to be a study involving appropriate statistical tests to examine the stability of sympathetic BRS within an experimental session and the repeatability between separate sessions. The aim of this study was to use intra-class correlations, ordinary least products regression, and Bland–Altman analyses to examine the stability and repeatability of spontaneous sympathetic BRS assessment. In addition, the influence of recording duration on values of BRS was assessed. In eighty-four healthy young individuals (49 males, 35 females), continuous measurements of blood pressure, heart rate and muscle sympathetic nerve activity (MSNA) were recorded for 10 min. In a subgroup of 13 participants (11 male, 2 female) the measurements were repeated on a separate day. Sympathetic BRS was quantified using MSNA burst incidence (BRSinc) and total MSNA (BRStotal) for the first 5-min period, the second 5-min period, and a 2-min segment taken from the second 5-min period. Intra-class correlation coefficients indicated moderate stability in sympathetic BRSinc and BRStotal between the first and second 5-min periods in males (BRSinc r = 0.63, BRStotal r = 0.78) and females (BRSinc r = 0.61, BRStotal r = 0.47) with no proportional bias, but with fixed bias for BRSinc in females. When comparing the first 5-min with the 2-min period (n = 76), the intra-class correlation coefficient indicated poor to moderate repeatability in sympathetic BRSinc and BRStotal for males (BRSinc r = -0.01, BRStotal r = 0.70) and females (BRSinc r = 0.46, BRStotal r = 0.39). However, Bland–Altman analysis revealed a fixed bias for BRStotal in males and proportional bias for BRStotal in females, with lower BRS values for 5-min recordings. In the subgroup, intra-class correlations indicated moderate repeatability for measures of BRSinc (9 male, 2 female, r = 0.63) and BRStotal (6 male, 2 female, r = 0.68) assessed using 5-min periods recorded on separate days. However, Bland–Altman analysis indicated proportional bias for BRSinc and fixed bias for BRStotal. In conclusion, measures of spontaneous sympathetic BRS are moderately stable and repeatable within and between testing sessions in healthy young adults, provided that the same length of recording is used when making comparisons.

Femoral vascular conductance and peroneal muscle sympathetic nerve activity responses to acute epidural spinal cord stimulation in humans.

What is the central question of this research? Does acute spinal cord stimulation increase vascular conductance and decrease muscle sympathetic nerve activity in the lower limbs of humans? What is the main finding and its importance? Acute spinal cord stimulation led to a rapid rise in femoral vascular conductance, and peroneal muscle sympathetic nerve activity demonstrated a delayed reduction that was not associated with the initial increase in femoral vascular conductance. These findings suggest that neural mechanisms in addition to attenuated muscle sympathetic nerve activity might be involved in the initial increase in femoral vascular conductance during acute spinal cord stimulation. Clinical cases have indicated an increase in peripheral blood flow after continuous epidural spinal cord stimulation (SCS) and that reduced muscle sympathetic nerve activity (MSNA) might be a potential mechanism. However, no studies in humans have directly examined the effects of acute SCS (<60min) on vascular conductance and MSNA. In study 1, we tested the hypothesis that acute SCS (<60min) of the thoracic spine would lead to increased common femoral vascular conductance, but not brachial vascular conductance, in 11 patients who previously underwent surgical SCS implantation for management of neuropathic pain. Throughout 60min of SCS, common femoral artery conductance was elevated and significantly different from brachial artery conductance [in millilitres per minute: 15min, change (Δ) 26±37 versus Δ-2±19%; 30min, Δ28±45 versus Δ0±26%; 45min, Δ48±43 versus Δ2±21%; 60min, Δ36±61 versus Δ1±24%; and 15min post-SCS, Δ51±64 versus Δ6±33%; P=0.013]. A similar examination in a patient with cervical SCS revealed minimal changes in vascular conductance. In study 2, we examined whether acute SCS reduces peroneal MSNA in a subset of SCS patients (n=5). The MSNA burst incidence in response to acute SCS gradually declined and was significantly reduced at 45 and 60min of SCS (in bursts per 100heart beats: 15min, Δ-1±12%; 30min, Δ-14±12%; 45min, Δ-19±16%; 60min, Δ-24±18%; and 15min post-SCS: Δ-11±7%; P=0.015). These data demonstrate that acute SCS rapidly increases femoral vascular conductance and reduces peroneal MSNA. The gradual reduction in peroneal MSNA observed during acute SCS suggests that neural mechanisms in addition to attenuated MSNA might be involved in the acute increase in femoral vascular conductance.

Direct Recording of Cardiac and Renal Sympathetic Nerve Activity Shows Differential Control in Renovascular Hypertension.

There is increasing evidence that hypertension is initiated and maintained by elevated sympathetic tone. Increased sympathetic drive to the heart is linked to cardiac hypertrophy in hypertension and worsens prognosis. However, cardiac sympathetic nerve activity (SNA) has not previously been directly recorded in hypertension. We hypothesized that directly recorded cardiac SNA levels would be elevated during hypertension and that baroreflex control of cardiac SNA would be impaired during hypertension. Adult ewes either underwent unilateral renal artery clipping (n=12) or sham surgery (n=15). Two weeks later, electrodes were placed in the contralateral renal and cardiac nerves to record SNA. Baseline levels of SNA and baroreflex control of heart rate and sympathetic drive were examined. Unilateral renal artery clipping induced hypertension (mean arterial pressure 109±2 versus 91±3 mm Hg in shams; P<0.001). The heart rate baroreflex curve was shifted rightward but remained intact. In the hypertensive group, cardiac sympathetic burst incidence (bursts/100 beats) was increased (39±14 versus 25±9 in normotensives; P<0.05), whereas renal sympathetic burst incidence was decreased (69±20 versus 93±8 in normotensives; P<0.01). The renal sympathetic baroreflex curve was shifted rightward and showed increased gain, but there was no change in the cardiac sympathetic baroreflex gain. Renovascular hypertension is associated with differential control of cardiac and renal SNA; baseline cardiac SNA is increased, whereas renal SNA is decreased.

Sympathetic activation in chronic anxiety: not just at the "height" of stress. Editorial Focus on "Relative burst amplitude of muscle sympathetic nerve activity is an indicator of altered sympathetic outflow in chronic anxiety".

Sympathetic activation in chronic anxiety: not just at the "height" of stress. Editorial Focus on "Relative burst amplitude of muscle sympathetic nerve activity is an indicator of altered sympathetic outflow in chronic anxiety".

Acute effects of device-guided slow breathing on sympathetic nerve activity and baroreflex sensitivity in posttraumatic stress disorder.

Patients with posttraumatic stress disorder (PTSD) have elevated sympathetic nervous system reactivity and impaired sympathetic and cardiovagal baroreflex sensitivity (BRS). Device-guided slow breathing (DGB) has been shown to lower blood pressure (BP) and sympathetic activity in other patient populations. We hypothesized that DGB acutely lowers BP, heart rate (HR), and improves BRS in PTSD. In 23 prehypertensive veterans with PTSD, we measured continuous BP, ECG, and muscle sympathetic nerve activity (MSNA) at rest and during 15 min of DGB at 5 breaths/min ( n = 13) or identical sham device breathing at normal rates of 14 breaths/min (sham; n = 10). Sympathetic and cardiovagal BRS was quantified using pharmacological manipulation of BP via the modified Oxford technique at baseline and during the last 5 min of DGB or sham. There was a significant reduction in systolic BP (by -9 ± 2 mmHg, P < 0.001), diastolic BP (by -3 ± 1 mmHg, P = 0.019), mean arterial pressure (by -4 ± 1 mmHg, P = 0.002), and MSNA burst frequency (by -7.8 ± 2.1 bursts/min, P = 0.004) with DGB but no significant change in HR ( P > 0.05). Within the sham group, there was no significant change in diastolic BP, mean arterial pressure, HR, or MSNA burst frequency, but there was a small but significant decrease in systolic BP ( P = 0.034) and MSNA burst incidence ( P = 0.033). Sympathetic BRS increased significantly in the DGB group (-1.08 ± 0.25 to -2.29 ± 0.24 bursts·100 heart beats-1·mmHg-1, P = 0.014) but decreased in the sham group (-1.58 ± 0.34 to -0.82 ± 0.28 bursts·100 heart beats-1·mmHg-1, P = 0.025) (time × device, P = 0.001). There was no significant difference in the change in cardiovagal BRS between the groups (time × device, P = 0.496). DGB acutely lowers BP and MSNA and improves sympathetic but not cardiovagal BRS in prehypertensive veterans with PTSD. NEW & NOTEWORTHY Posttraumatic stress disorder is characterized by augmented sympathetic reactivity, impaired baroreflex sensitivity, and an increased risk for developing hypertension and cardiovascular disease. This is the first study to examine the potential beneficial effects of device-guided slow breathing on hemodynamics, sympathetic activity, and arterial baroreflex sensitivity in prehypertensive veterans with posttraumatic stress disorder.

Role of Corin in Neuro‐Circulatory and Renal‐Adrenal Control during Pregnancy in Humans

Corin (an atrial natriuretic peptide converting enzyme) represents a key regulator of cardiovascular and renal function through its influence on blood pressure (BP) and salt‐water balance, respectively. Recently, corin has been identified as a potential contributor to the pathogenesis of preeclampsia. However, the role of corin in BP regulation and renal function during pregnancy remains uncertain. Therefore, the objective of the current study was to investigate the role played by corin in the neuro‐circulatory adjustments and renal‐adrenal response during pregnancy. We evaluated prospectively, in 30 healthy women [30±4 (SD) yrs, 164±5 cm, 65±20 kg], BP (Suntech), heart rate (HR; electrocardiogram), and muscle sympathetic nerve activity (MSNA; microneurography) prior‐to pregnancy (mid‐luteal phase), during early‐(6.8±1.2 wks gestation) and late‐ (33.7±2.1 wks gestation) pregnancy, and post‐partum (8.3±1.2 wks post‐delivery). Venous blood samples were taken for the measurement of maternal serum corin content (ELISA) and direct renin (radio‐immunoassay) and aldosterone concentrations (chemiluminescent immunoassay). All women had singleton, full‐term pregnancies. Compared to pre‐pregnancy (1312±367 pg/mL), corin levels remained unchanged during early‐pregnancy (1368±351 pg/mL; P&gt;0.05), increased markedly during late‐pregnancy (2046±651 pg/mL; P&lt;0.001), and returned to pre‐pregnancy levels following delivery (1265±315 pg/mL; P&gt;0.05). During early‐ and late‐pregnancy, corin content was related moderately to mean arterial BP (R=0.510; P&lt;0.001). Similarly, corin levels were related, albeit modestly, to MSNA burst frequency (R=0.357; P&lt;0.01) and burst incidence (R=0.338; P=0.01), as well as direct renin (R=0.374; P&lt;0.05) and aldosterone (R=0.319; P&lt;0.05) concentrations. In a subset of eight women who developed gestational hypertensive disorders during their pregnancies, the change in corin levels from early‐ to late‐pregnancy tended to be greater than in those with normotensive pregnancies, although considerable individual variability existed (Δ 974±706 vs. Δ 493±457 pg/mL; P=0.06). Throughout pregnancy, mean arterial BP was greater in women with hypertensive pregnancies (Pre: 79±4; Early: 76±6; Late: 81±7; Post: 77±4 mmHg) compared to those with normotensive pregnancies (Pre: 77±4; Early: 71±5; Late: 76±6; Post: 74±4 mmHg; P&lt;0.01 for group). Similarly, MSNA burst frequency was greater in women with hypertensive pregnancies (Pre: 18±5; Early: 23±12; Late: 28±13; Post: 13±13 bursts/min) than in those with normotensive pregnancies (Pre: 10±6; Early: 14±9; Late: 22±14; Post: 9±7 bursts/min; P&lt;0.05 for group). In conclusion, corin increases during late pregnancy and appears to be moderately associated with BP regulation. Whether corin represents a key regulator of neuro‐circulatory control and renal‐adrenal responses during pregnancy, or plays a unique role in the development of gestational hypertensive disorders, remains uncertain but represents a novel target for future investigation.Support or Funding InformationNIH R21 (HLO88184); AHA Grant‐in‐Aid award (13GRNT16990064); Harry S. Moss Heart TrustThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sleep Deprivation and Sympathetic Neural Control in Older Adults

Epidemiological studies have suggested a link between sleep deprivation and hypertension, and that this link is stronger in women. Our laboratory recently reported that baseline sympathetic neural responses to total sleep deprivation (TSD) were different in young men and women, with a greater shift towards sympathetic predominance in young women. Postmenopausal women are at high risk for hypertension. In the present study, we hypothesize that TSD will alter sympathetic neural activity in older adults, with greater sympathoexcitation in postmenopausal women. Nine participants between the ages of 55 and 75 years (9 women and 7 men) participated in the study. Subjects were tested twice one month apart, once after 24‐hour TSD and once after normal sleep. Wrist actigraphy was worn 5 days prior to each testing to confirm normal sleep patterns. We recorded muscle sympathetic nerve activity (MSNA; microneurography), beat‐to‐beat blood pressure (finger plethsmography), and heart rate (electrocardiogram) during 5 min of supine, awake rest. TSD elicited divergent MSNA responses in older men and women. Specifically, MSNA burst frequency increased in postmenopausal women (31±3 to 35±3 burst/min), but not older men (39±3 to 36±4 burst/min; time × condition, p = 0.036). This shift towards sympathetic predominance in women was also observed when MSNA was quantified as burst incidence (time × condition, p = 0.034). TSD did not alter baseline mean arterial pressure (men, 89±5 to 87±3 mmHg; women, 84±4 to 84±3) or heart rate (men, 55±3 to 55±4 beats/min; 58±3 to 60±4 beats/min) in either group (time, p&gt;0.05; time × condition, p&gt; 0.05). In summary, 24‐hour TSD elicits divergent MSNA responses in older men and women, with greater sympathoexcitation in postmenopausal women. These findings provide new mechanistic insight into reported links between sleep deprivation and hypertension.Support or Funding InformationFunding support from the National Institutes of Health (HL‐122919) and Portage Health Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sympathetic Baroreflex Sensitivity During Mental Stress in Humans With Chronic Anxiety

Elevated muscle sympathetic nerve activity (MSNA) is associated with the pathogenesis of hypertension and cardiac arrhythmias, and may be related to greater cardiovascular disease (CVD) risk among individuals with chronic anxiety. Augmented sympathetic responsiveness in chronic anxiety may potentially be attributed to alteration in sympathetic baroreflex control. We hypothesized that MSNA and its responsiveness to stress would be augmented in chronic anxiety, and that augmented MSNA responsiveness would be related to impaired sympathetic baroreflex sensitivity. Sympathetic baroreflex sensitivity was assessed by relating spontaneous changes in multi‐unit MSNA to beat‐to‐beat changes in diastolic blood pressure (DBP) using a weighted linear regression at rest (10 min) and during mental stress (MS, 4‐min mental arithmetic) in 18 individuals with moderate/high chronic anxiety (ANX, 6 men/12 women; 32±2 yrs; 27±2 kg/m2) who were nonsmokers and free of CVD, and in 18 healthy controls with low/no anxiety (CON, 8 men/10 women; 39±3 yrs; 30±1 kg/m2). Resting MSNA was not elevated among ANX compared to CON (MSNA burst incidence: ANX 29 ± 5 vs. CON 40 ± 4 bursts/100hb; Avg. relative MSNA burst amplitude: ANX 48 ± 1 vs. CON 47 ± 1 AU). Avg. relative MSNA burst amplitude in response to MS was significantly augmented among ANX compared to CON (ANX: 61 ± 2 vs. CON: 54 ± 2 AU, P=0.02), while % change in MSNA burst incidence was not significantly different between ANX and CON (ANX: 4 ± 7 vs. CON: 6 ± 7 bursts/100hb, P=0.86). Increases in avg. relative MSNA burst amplitude during MS were significantly correlated with trait anxiety score among all participants after adjusting for age, sex, and BMI (R=0.48, P=0.01). The slope between MSNA burst incidence and DBP was not different between ANX and CON at rest (ANX: −2.8 ± 0.6 vs. CON: −3.5 ± 0.5 bursts/100hb/mmHg−1, P=0.35), and was significantly reduced during MS (P=0.03) with no difference between ANX and CON (ANX: −2.2 ± 0.4 vs. CON: −2.3 ± 0.5 bursts/100hb/mmHg−1, P=0.42). The slope between total MSNA and diastolic BP was similar between ANX and CON at rest (ANX: −1.5 ± 0.3 vs. CON: −1.9 ± 0.3 AU/beat/mmHg−1, P=0.3) and unchanged (P=0.49) during MS (ANX: −1.5 ± 0.3 vs. CON: −1.5 vs. 0.3 AU/beat/mmHg−1, P=0.99). These preliminary findings demonstrate that individuals with chronic anxiety exhibit augmented increases in MSNA burst amplitude but not burst incidence to mental stress, and this alteration in the MSNA response to mental stress in chronic anxiety is not a result of impairment in sympathetic baroreflex sensitivity.Support or Funding InformationAHA 17POST33440101, T32 HL07121 NHLBI (P01HL014388), U54 TR001356 and AHA (13DG143400012)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Differential Sympathetic and RAAS Responses to a Low Sodium Diet

A common sodium recommendation intake target is 2300 mg/d; however the AHA has stated that no more than 1500 mg per day is ideal. Concerns have been expressed that reducing sodium intake too low could lead to maladaptive sympathetic and RAAS responses and some of this concern comes from studies where sodium/volume depletion diets were used (as low as 230 mg/d sodium).PURPOSETo assess the sympathetic and RAAS responses of reducing sodium intake from the widely recommended 2300 mg/d to &lt;1500 mg/d. We hypothesized that this level of sodium restriction would stimulate RAAS but not increase sympathetic activity, since this level of sodium intake should not cause severe sodium/volume depletion.METHODSEight subjects (age: 25±1 yrs, BMI: 23.4±3.9 kg/m2, 4 men) consumed 2300 mg Na+/day and 1000 mg Na+/day sodium diets (order randomized) for 10 days each. Subjects collected their urine for the final 24 hours preceding in‐lab testing. Testing was performed on the last day of each diet. Blood samples were collected for assessment of catecholamines and RAAS hormones. Angiotensin II and aldosterone concentrations were assessed in six of eight subjects. Subjects then lay quietly for 10 minutes while undergoing recording of beat‐to‐beat blood pressure (via photoplethysmography), R‐R interval (via 3‐lead ECG), and muscle sympathetic nerve activity (MSNA) (via microneurography).RESULTSTwenty‐four hour urinary sodium excretion was significantly lower when dietary sodium was reduced to 1000 mg/d (93±8 vs. 45±12 mmol/24 hrs, P&lt;0.01). Resting mean arterial pressure was not different following either diet (81±2 vs. 81±2 mmHg, P&gt;0.20). Reducing sodium intake to 1000 mg/d increased plasma renin activity (1.5±0.3 vs. 2.2±0.4ng/mL/hr, P&lt;0.05), angiotensin II concentration (12.5±1.5 vs. 19.1±3.2 pg/mL, P&lt;0.05), and aldosterone (11.7±1.3 vs. 20.4±4.6 ng/mL, P=0.052). However, reducing sodium intake to 1000 mg/d did not alter MSNA burst frequency (13.8±0.9 vs. 13.0±1.2 bursts/min, P&gt;0.20), burst incidence (23.9±2.3 vs. 21.8±3.0 bursts/100 heart beats, P&gt;0.20), or plasma norepinephrine concentrations (237±46 vs. 173±57 pg/mL, P&gt;0.20).CONCLUSIONThese preliminary data suggest that reducing sodium from 2300 mg/d to 1000 mg/d stimulates RAAS but does not alter resting MSNA or catecholamines in healthy young adults. These findings suggest that diets as low as 1000 mg Na+/day can be consumed without stimulating the sympathetic nervous system.Support or Funding InformationSupported by NIH Grant 1R01HL128388This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Spontaneous Baroreflex Control of Muscle Sympathetic Nerve Activity in Humans: Standardizing Analysis Procedures

Beat‐to‐beat variations in muscle sympathetic nerve activity (MSNA) are strongly related to diastolic blood pressure (DBP) fluctuations, and the use of spontaneous occurring bursts of MSNA at rest to determine sympathetic baroreflex sensitivity has become more prevalent. However, published results using spontaneous sympathetic baroreflex sensitivity have lacked standard methodology for analysis. Indeed, there have been variations in the duration of the recording used, the size of the DBP bins (1‐, 2‐, 3‐mmHg), and strength of the linear regression r‐values accepted. Thus, we sought to comprehensively examine the influence of these varying analysis procedures on spontaneous sympathetic baroreflex sensitivity. Our goal was to provide a standardized procedure that would allow for consistent and comparable results across laboratories. In a collective group of subjects (n=150), weighted linear regression analysis between MSNA and DBP was performed with MSNA expressed as either burst incidence (bursts/100heartbeats) or total MSNA (summation of MSNA burst amplitude relative to number of cardiac cycles). Resting MSNA was analyzed over a 10‐min baseline period, and subsequently segregated into separate 5‐, 2‐, and 1‐min segments to examine the influence of baseline duration on the weighted linear regression. MSNA was averaged over 1‐, 2‐, or 3‐mmHg DBP ranges (bins) to examine the influence of bin size. Also, in a subset of subjects (n=35), the modified Oxford technique (intravenous infusion of sodium nitroprusside followed by phenylephrine) was performed for comparison. The average slope of the linear regressions for resting MSNA burst incidence and total MSNA progressively increased as the baseline duration decreased with 1‐min duration being significantly greater than 10 min (P&lt;0.05); however, correlation coefficients were reduced with the shorter durations. Indeed, the 10‐min baseline durations most frequently yielded statistically significant probability values for linear regressions (P&lt;0.05), which closely reflected the p‐values obtained during the modified Oxford. Interestingly, although bin size (1‐, 2‐, 3‐mmHg) had no major influence on the average slope of the regressions (P&gt;0.05), correlation coefficients progressively increased with bin size such that the highest correlation coefficients were observed for the 3‐mmHg bin size for each time duration segment. Overall, the 10‐min durations and 3‐mmHg bin size yielded the highest correlation coefficients. Collectively, these findings suggest that the duration of the recording used for analysis impacts the statistical validity of the r‐values defining the slopes for spontaneous sympathetic baroreflex sensitivity, whereas larger bin size improves the r‐value but has less influence on the p‐value.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Training Heart Failure Patients with Reduced Ejection Fraction Attenuates their Muscle Metaboreflex and Lowers Muscle Sympathetic Nerve Activity at Rest and During Mild Dynamic Exercise

We have shown that muscle sympathetic nerve activity (MSNA) is elevated at rest in patients with heart failure due to reduced ejection fraction (HFrEF) and, in contrast to healthy subjects, increases during moderate dynamic 1‐leg exercise. We hypothesized that exercise training in HFrEF may reduce MSNA during both mild and moderate intensity 1‐leg dynamic exercise and static handgrip; attenuate the muscle metaboreflex; and improve skin blood flow. We studied 27 stable, medicated HFrEF patients (6 women; mean age 65 ± 2 SE [range 42 to 80] years; mean left ventricular ejection fraction 30 ± 1% [range 12–40]); of either ischemic (n=18) or non‐ischemic (n=9) etiology, both before and after 6 months of cardiac rehabilitation (aerobic exercise for 45 minutes, 5 times per week at 60–70 % of VO2peak); plus 18 healthy, age and sex‐matched, medication‐free volunteers (6 women; mean age 57 ± 2 [range 48 to 72]). Before and after training, we assessed VO2peak (open‐circuit spirometry); the skin blood flow (SBF) response to reactive hyperemia (laser flowtometry); and fibular MSNA (microneurography) at rest (n=18), during 1‐leg cycling (2 min each unloaded and at 50% of VO2peak, n=16) and, to assess the muscle metaboreflex, during post‐handgrip ischemia (PHGI) after 2 min of 30% static handgrip (HG). In HFrEF, pre‐training VO2peak and skin vasodilatation were lower (P&lt;0.001) and resting MSNA higher compared to controls (P=0.01). Exercise training improved VO2peak by 3.0±1.0 ml·kg−1·min−1 (P&lt;0.001) and increased the SBF vasdilatory response in HFrEF to a mean value similar to controls (P=0.78). Relative to pre‐training, resting MSNA decreased by 6.0±2.0 bursts/min (P=0.01, N=18) and 7.3±3.4 burst/100 heartbeats (P=0.04). During 1‐leg cycling, MSNA decreased in control (P=0.01) but increased in HFrEF (P&lt;0.001). Exercise training attenuated MSNA burst frequency and incidence during unloaded (P=0.04) but not loaded cycling (P=0.34). The rise in MSNA burst frequency during HG in HFrEF was unaffected by training, but its elevation during PHGI was abolished (P&lt;0.05). We conclude that the exaggerated metaboreflex of HFrEF is attenuated by exercise training. This may contribute to a lower MSNA during mild but not moderate intensity cycling.Support or Funding InformationSupported by Heart and Stroke Foundation of Ontario and Canadian Institutes for Health ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impaired Arterial Baroreflex Sensitivity in Prehypertension

Prehypertension is associated with increased risk of hypertension and cardiovascular disease (CVD). The physiological mechanisms underlying this risk are unknown, and the appropriate therapeutic approach to this preclinical but high‐risk population remain unclear. Previous studies have shown increased resting sympathetic nerve activity, as well as augmented blood pressure (BP) responses during mental stress in prehypertension, suggesting autonomic dysregulation at rest and during stress. We hypothesized that compared to normotensive controls (BP ≤ 120/80 mm Hg), prehypertensives (BP 120/80–139/89 mm Hg) have impaired arterial baroreflex sensitivity (BRS), the major feedback system regulating autonomic tone in response to BP changes, as well as increased neurocardiovascular reactivity to mental stress. Twenty‐two participants were studied; 12 otherwise healthy prehypertensives (age 35±6 years) were compared to 10 normotensive controls (age 32±6 years,) matched for age, gender, race, and body mass index. We recorded muscle sympathetic nerve activity (MSNA) using microneurography, beat‐to‐beat arterial BP, and heart rate (HR) via continuous EKG during five minutes of supine rest and three minutes of mental stress induced via mental arithmetic. We measured resting arterial baroreflex sensitivity (BRS) using the modified oxford technique in which IV boluses of nitroprusside and phenylephrine were infused to manipulate arterial BP. The slope of the linear relationship between diastolic BP and MSNA burst incidence was assessed for sympathetic BRS, and between change in systolic BP and R‐R interval for cardiovagal BRS. As expected, baseline systolic BP (130±7 vs. 117±8 mmHg) and diastolic BP (87±7 vs. 74±8 mmHg) were significantly higher in prehypertensives (p&lt;0.001), but HR (70±10 vs. 66±13 beats/min, p&gt;0.05) was comparable between the groups. Resting MSNA (25±12 vs. 18±10 bursts/min) tended to be higher in prehypertensives (p=0.08). Sympathetic BRS was comparable between the groups at rest, but cardiovagal BRS (13±10 vs. 22±10 ms/mmHg) was significantly lower in prehypertensives (p=0.03). During mental arithmetic, minute‐by‐minute increases in BP, HR and MSNA did not differ between the groups. There was a significant positive correlation between the diastolic BP response during mental stress and resting cardiovagal BRS (r=0.703, p=0.016), and with sympathetic BRS (r=0.795, p=0.010) within the prehypertensive group. However, there was no significant relationship between BP responses during mental stress with cardiovagal (r=0.126, p=0.766) or sympathetic BRS (r=0.287, p=0.581) in normotensive controls. These findings suggest that an early impairment of arterial BRS may be present in prehypertension and may modulate BP responses to stress, contributing to increased hypertension and CVD risk.Support or Funding InformationSupported by NIH HL‐098744, NIH DK‐00756, VA Merit I01CX001065, AHA 15CSA24340001This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Relationship Between Sympathetic Baroreflex Sensitivity And Vascular Transduction

Sympathetic baroreflex sensitivity (BRS) is a tool used to quantify how effectively the baroreflex buffers beat‐to‐beat changes in blood pressure. However, current methods of assessment do not take into account vascular transduction, i.e. the response of the peripheral vasculature to vasoconstrictor drive. The aim of the study was to investigate the relationship between sympathetic BRS and vascular transduction. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure, heart rate and superficial femoral artery blood flow (Doppler ultrasound) were recorded at rest for 5 min in 28 healthy adults (18–31yrs, 13 males, 15 females). Sympathetic BRS was quantified by plotting MSNA burst incidence against mean diastolic pressure using 3 mmHg bins. For vascular transduction, the % change in leg vascular conductance was determined for 15 cardiac cycles following each MSNA burst and the nadir of the response was calculated. Linear regression analysis was used to examine the relationship between sympathetic BRS and vascular transduction in males and females separately. Sympathetic BRS was not significantly different between males (−2.9± 1.8) and females (−3.2 ± 1.6 %bursts/mmHg, p=0.68). However, vascular transduction was significantly lower in males (−5.5 ± 4.1) compared with females (9.1 ± 4.7 %change in ml/min/mmHg, p=0.04). In males there was a significant inverse relationship between sympathetic BRS and vascular transduction (r=0.78, p=0.002), but in females there was no significant relationship (r=0.34, p=0.21). The results suggest that in males those with high sympathetic BRS have low vascular transduction, and vice versa. This may represent a compensatory effect to ensure that blood pressure is regulated effectively. However, this relationship between sympathetic BRS and vascular transduction was not apparent in young females.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Relative burst amplitude of muscle sympathetic nerve activity is an indicator of altered sympathetic outflow in chronic anxiety.

Relative burst amplitude of muscle sympathetic nerve activity (MSNA) is an indicator of augmented sympathetic outflow and contributes to greater vasoconstrictor responses. Evidence suggests anxiety-induced augmentation of relative MSNA burst amplitude in patients with panic disorder; thus we hypothesized that acute stress would result in augmented relative MSNA burst amplitude and vasoconstriction in individuals with chronic anxiety. Eighteen participants with chronic anxiety (ANX; 8 men, 10 women, 32 ± 2 yr) and 18 healthy control subjects with low or no anxiety (CON; 8 men, 10 women, 39 ± 3 yr) were studied. Baseline MSNA and 24-h blood pressure were similar between ANX and CON ( P > 0.05); however, nocturnal systolic blood pressure % dipping was blunted among ANX ( P = 0.02). Relative MSNA burst amplitude was significantly greater among ANX compared with CON immediately preceding (anticipation) and during physiological stress [2-min cold pressor test; ANX: 73 ± 5 vs. CON: 59 ± 3% arbitrary units (AU), P = 0.03] and mental stress (4-min mental arithmetic; ANX: 65 ± 3 vs. CON: 54 ± 3% AU, P = 0.02). Increases in MSNA burst frequency, incidence, and total activity in response to stress were not augmented among ANX compared with CON ( P > 0.05), and reduction in brachial artery conductance during cold stress was similar between ANX and CON ( P = 0.92). Relative MSNA burst amplitude during mental stress was strongly correlated with state ( P < 0.01) and trait ( P = 0.01) anxiety (State-Trait Anxiety Inventory), independent of age, sex, and body mass index. Thus in response to acute stress, both mental and physiological, individuals with chronic anxiety demonstrate selective augmentation in relative MSNA burst amplitude, indicating enhanced sympathetic drive in a population with higher risk for cardiovascular disease. NEW & NOTEWORTHY Relative burst amplitude of muscle sympathetic nerve activity in response to acute mental and physiological stress is selectively augmented in individuals with chronic anxiety, which is a prevalent condition that is associated with the development of cardiovascular disease. Augmented sympathetic burst amplitude occurs with chronic anxiety in the absence of common comorbidities. These findings provide important insight into the relation between anxiety, acute stress and sympathetic activation.

Analytical Determination of Energy Release in a Coal Mass

In underground mining, it is not currently feasible to forecast a coal burst incident. A coal burst usually includes suddenly abrupt energy release in line with the significant deformed shape in a coal mass as well as coal ejection. The major source of the released energy is the energy stored in the coal. The effect of geological characteristics in the coal on the possible released energy due to material and joint damping is classified as a current silent issue. Therefore, innovative research is needed to understand the influence of coal’s joint and cleat characters (directions and densities) on the possible energy release and/or dissipation. A simple and novel analytical solution is developed in this paper to calculate the amount of released energy due to varying joint density. A broad validation is conducted by comparing the outcomes of the developed analytical model with the results of a three-dimensional numerical simulation using the commercial discrete element package 3DEC. An appropriate agreement has been observed between the results from the numerical modelling and the suggested closed form solution. The paper derives a novel analytical solution to calculate the amount of released energy in coal with different joint densities.

Effects of weight changes in the autonomic nervous system: A systematic review and meta-analysis

Obesity has been linked to autonomic dysfunction, which is thought to be one of the main contributors for hypertension, cardiac remodelling and death. Exercise and diet-based weight loss are the mainstay therapy for obesity, but there is a paucity of data regarding the effect of weight changes in autonomic nervous system (ANS) activity. To describe the impact of weight changes in autonomic nervous system. A systematic literature search of four biomedical databases was performed evaluating effects of weight changes, thorough diet and/or exercise-based interventions, in the following ANS outcomes: heart rate variability, namely low frequency (LF)/high frequency (HF) ratio (LF/HF ratio), normalized units of LF (LFnu) and HF (HFnu), muscle sympathetic nerve activity (MSNA), noradrenaline spillover rate (NA-SR), standard deviation of normal-to-normal intervals (SDNN), root mean square of successive differences (RMSSD), baroreflex sensitivity and pupillometry. Quality appraisal was performed using the GRADE methodology and, where fitting, studies with comparable outcomes were pooled for meta-analysis. Twenty-seven studies - 7 controlled clinical trials and 20 observational studies - were included. Weight gain was reported in 4 studies and weight loss in all the other studies. Interventions inducing weight changes included: hypocaloric or hypercaloric diets, exercise (strength, endurance or aerobic training) and hypocaloric diet coupled with exercise programs. Most studies which resulted in weight loss reported decreases in LF/HF ratio, LFnu, MSNA burst frequency and incidence, NA-SR, and an increase of baroreflex sensitivity, HF, HFnu and RMSSD, pointing to a parasympathetic nervous system activation. Meta-analysis regarding weight loss interventions showed a significant pooled effect size (95% CI) with a decreased of MSNA burst frequency-5.09 (-8.42,-1.75), MSNA incidence-6.66 (-12.40,-0.62), however this was not significant for SDNN 14.32 (-4.31, 32.96). Weight gain was associated with an increase in LF/HF, LFnu, MSNA burst frequency and incidence. The weight loss effects were potentiated by the association of hypocaloric diet with exercise. Nevertheless, weight changes effects in these outcomes were based in low or very low quality of evidence. Diet and exercise based weight loss appears to increase parasympathetic and decrease sympathetic activity, the opposing effects being observed with weight gain. These findings are not uniformly reported in the literature, possibly due to differences in study design, methodology, characteristics of the participants and techniques used to estimate autonomic nervous activity.