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The hypoxic chemoreflex and the arterial baroreflex are implicated in the ventilatory response to exercise. It is well known that long-term exercise training increases parasympathetic and decreases sympathetic tone, both processes influenced by the arterial baroreflex and hypoxic chemoreflex function. Hypobaric hypoxia (i.e., high altitude [HA]) markedly reduces exercise capacity associated with autonomic reflexes. Indeed, a reduced exercise capacity has been found, paralleled by a baroreflex-related parasympathetic withdrawal and a pronounced chemoreflex potentiation. Additionally, it is well known that the baroreflex and chemoreflex interact, and during activation by hypoxia, the chemoreflex is predominant over the baroreflex. Thus, the baroreflex function impairment may likely facilitate the exercise deterioration through the reduction of parasympathetic tone following acute HA exposure, secondary to the chemoreflex activation. Therefore, the main goal of this review is to describe the main physiological mechanisms controlling baro- and chemoreflex function and their role in exercise capacity during HA exposure. [ABSTRACT FROM AUTHOR]

Background: Autonomic function and baroreflex control might influence the survival rate of coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU) compared to respiratory failure patients without COVID-19 (non-COVID-19). This study describes physiological control mechanisms in critically ill COVID-19 patients admitted to the ICU in comparison to non-COVID-19 individuals with the aim of improving stratification of mortality risk. Methods: We evaluated autonomic and baroreflex control markers extracted from heart period (HP) and systolic arterial pressure (SAP) variability acquired at rest in the supine position (REST) and during a modified head-up tilt (MHUT) in 17 COVID-19 patients (age: 63 ± 10 years, 14 men) and 33 non-COVID-19 patients (age: 60 ± 12 years, 23 men) during their ICU stays. Patients were categorized as survivors (SURVs) or non-survivors (non-SURVs). Results: We found that COVID-19 and non-COVID-19 populations exhibited similar vagal and sympathetic control markers; however, non-COVID-19 individuals featured a smaller baroreflex sensitivity and an unexpected reduction in the HP-SAP association during the MHUT compared to the COVID-19 group. Nevertheless, none of the markers of the autonomic and baroreflex functions could distinguish SURVs from non-SURVs in either population. Conclusions: We concluded that COVID-19 patients exhibited a more preserved baroreflex control compared to non-COVID-19 individuals, even though this information is ineffective in stratifying mortality risk. [ABSTRACT FROM AUTHOR]

The baroreflex is a powerful physiological mechanism for rapidly adjusting heart rate in response to changes in blood pressure. Spontaneous baroreflex sensitivity (BRS) has been shown to decrease with age. However, studies of sex differences in these age-related changes are rare. Here we investigated several markers of spontaneous baroreflex function in a large sample of healthy individuals. Cardiovascular signals were recorded in the supine position under carefully controlled resting conditions. After quality control, n = 980 subjects were divided into five age groups [age < 30 yr (n = 612), 30-39 yr (n = 140), 40-49 yr (n = 95), 50-59 yr (n = 61), and >60 yr (n = 72)]. Spontaneous baroreflex function was assessed in the time domain (bradycardic and tachycardic slope) and in the frequency domain in the low- and high-frequency band (LF-a, HF-a) applying the transfer function. General linear models showed a significant effect of factor age (P < 0.001) and an age - sex interaction effect (P < 0.05) on each indicator of the baroreflex function. Simple main effects showed a significantly higher BRS as indicated by tachycardic slope, LF-a and HF-a in middle-aged women compared with men (30-39 yr) and higher LF-a, bradycardic and tachycardic slope in men compared with women of the oldest age group (>60 yr). Changes in BRS over the lifespan suggest that baroreflex function declines more slowly but earlier in life in men than in women. Our findings could be linked to age-related changes in major sex hormone levels, suggesting significant implications for diverse cardiovascular outcomes and the implementation of targeted preventive strategies. [ABSTRACT FROM AUTHOR]

Background: E-learning based laboratory classes can replace or enhance in-classroom laboratories. They typically offer temporal flexibility, self-determined learning speed, repeatability and do not require supervision or face-to-face contact. The aim of this feasibility study was to investigate whether the established in-classroom laboratory class on the baroreceptor reflex (BRR) can be transformed into a new e-learning based asynchronous laboratory class for untrained, non-supervised students without medical equipment. The BRR is a fundamental cardiovascular process which is regularly visualized in physiology during in-classroom laboratories by a student-performed Active Standing Test (AST). During this voluntary provocation of orthostatic stress, the BRR reliably causes a solid rise in heart rate (HR) and a stabilization or even increase in blood pressure (BP). Methods: The conventional AST was modified by omission of BP measurements which would require medical devices and was embedded into a framework of interactive digital material allowing independent student performance. With specific adaptions, this instrument was implemented to 1st and 2nd year curricula of human medicine, dental medicine, midwifery and pharmacy. An audience response system was used to collect the students' data on HR, epidemiology, technical problems, satisfaction and orthostatic symptoms. As primary outcome, we investigated the students' correct performance of the modified AST regarding textbook conformity of the HR data. Secondary outcomes included technical feasibility, the students' satisfaction and consistency of HR data within predefined subgroups (e.g., gender, curricula). Descriptive statistics are reported. Results: The class was completed by 217 students (mean age: 23 ± 8 [SD], 81% female, 19% male). Mean reported rise of HR during standing was ~ 20 bpm (~ 30%) which is highly concordant to textbooks. Reported feasibility (~ 80% negated any technical issues) and students' satisfaction (4.4 on 5-point Likert-scale) were high. The HR data were consistent within the subgroups. Conclusion: This study demonstrates that the highly relevant BRR can be successfully addressed in an e-learning based asynchronous laboratory class implementing a non-supervised AST restricted to HR measurements embedded in digital material. The robust HR response and the adjustable complexity allow an application to different healthcare-related curricula. This class, therefore, provides a broad audience access to a fundamental concept of cardiovascular physiology. [ABSTRACT FROM AUTHOR]

The arterial baroreceptor reflex in children and adolescents has not been well studied in the current literature with a lack of agreed upon normal values, particularly in postural orthostatic tachycardia syndrome (POTS) or neurocardiogenic syncope (NCS). We used the sequence method and head-up tilt test (HUTT) to evaluate baroreceptor function in 3 phases: baseline supine position for 10 min, head-up position at 70° for 30 min or until syncope, and post-tilt supine reposition for 10 min. We measured the number of baroreceptor events, baroreceptor effectiveness index (BEI), and the magnitude of sensitivity of the events at each phase of HUTT. We studied 198 individuals (49 normal subjects, 67 POTS, 82 NCS) with age ranges from 8 to 21 years. The data show a statistically significant decrease in slope and BEI in patients with POTS and NCS during the head-up phase, with an increase in activity in the lag 1 and 2 portions of all phases in patients with POTS. This study provides terminology to describe baroreceptor function and identifies the slope and BEI portions of the baroreceptor reflex as the most useful objective measures to differentiate pediatric patients with POTS and NCS from normal subjects. [ABSTRACT FROM AUTHOR]

Purpose: The aim is to evaluate and characterize cardiovascular autonomic control and baroreflex function and their response to an orthostatic stressor in the second trimester of pregnancy via time, frequency, information and symbolic analyses. Methods: We evaluated 22 women at 18 weeks of pregnancy, labeled as pregnant group (PG) (30.8±4.4 years), and 22 non-pregnant women (29.8±5.4 years), labeled as control group (CG). Electrocardiogram, non-invasive photoplethysmographic arterial pressure (AP) and respiratory signals were recorded at rest at left lateral decubitus (REST) and during active standing (STAND) for 10 minutes. The heart period (HP) variability and systolic AP (SAP) variability were assessed in the frequency domain. High frequency (HF) and low frequency (LF) spectral indexes were computed. Nonlinear indexes such as symbolic markers (0V%, 1V%, 2LV% and 2UV% indexes), Shannon entropy (SE) and normalized complexity index (NCI) were calculated as well. Baroreflex control was assessed by cross-spectral HP-SAP analysis. We computed baroreflex sensitivity (BRS), HP-SAP squared coherence (K2) and phase in LF and HF bands. Results: At REST, the PG had lower mean, variance and HF power of HP series and lower K2(LF), BRS(LF) and BRS(HF) than the CG. During STAND, CG and PG decreased the mean, CI, NCI and 2UV% and increased 0V% of the HP series and augmented the SAP variance. LFabs of SAP series increased during STAND solely in CG. BRS(HF) was reduced during in both PG and CG, while HFabs of HP series did not diminish during STAND either in PG or CG. Complexity of the autonomic control was similar in PG and CG regardless of the experimental condition. Conclusion: We conclude that the second trimester of pregnancy was characterized by a lower parasympathetic modulation and reduced BRS at REST, preserved complexity of cardiac and vascular controls, limited sympathetic response to STAND and general conservation of the baroreflex responses to posture changes. Trial registration: Begistro Brasileiro de Ensaios clínicos, Number: . [ABSTRACT FROM AUTHOR]

In this review, we highlight the underlying mechanisms responsible for the sex differences in the exercise pressor reflex (EPR), and, importantly, the impact of sex hormones and menopausal status. The EPR is attenuated in premenopausal women compared with age-matched men. Specifically, activation of the metaboreflex (a component of the EPR) results in attenuated increases in blood pressure and sympathetic vasomotor outflow compared with age-matched men. In addition, premenopausal women exhibit less transduction of sympathetic outflow to the peripheral vasculature than men. In stark contrast, postmenopausal women exhibit an augmented EPR arising from exaggerated metaboreflex-induced autonomic and cardiovascular reflexes. We propose that metaboreflex-induced autonomic and cardiovascular changes associated with menopause majorly contribute to the elevated blood pressure response during dynamic exercise in postmenopausal women. In addition, we discuss the potential mechanisms by which sex hormones in premenopausal women may impact the EPR as well as metaboreflex. [ABSTRACT FROM AUTHOR]

Purpose: Overload training is hypothesized to alter autonomic regulation, although interpretations using indirect measures of heart rate variability are conflicting. The aim of the present study was to examine the effects of overload training on muscle sympathetic nerve activity (MSNA), a direct measure of central sympathetic outflow, in recreational endurance athletes. Methods: Measurements of heart rate variability, cardiac baroreflex sensitivity (BRS), MSNA (microneurography), and sympathetic BRS were obtained in 17 healthy triathletes and cyclists after 1 wk of reduced training (baseline) and again after 3 wk of either regular (n = 7) or overload (n = 10) training. Results: After training, the changes (Δ) in peak power output (10 ± 10 vs -12 ± 9 W, P < 0.001), maximal heart rate (-2 ± 4 vs -8 ± 3 bpm, P = 0.006), heart rate variability (SD of normal-to-normal intervals, 27 ± 31 vs -3 ± 25 ms; P = 0.04), and cardiac BRS (7±6 vs -2 ± 8 ms-mm Hg-1, P = 0.02) differed between the control and overload groups. The change in MSNA burst frequency (-2 ± 2vs4 ± 5 bursts per minute, P = 0.02) differed between groups. Across all participants, the changes in resting MSNA and peak power output were correlated negatively (r = -0.51, P = 0.04). No between-group differences in resting heart rate or blood pressure were observed (all P > 0.05). Conclusions: Overload training increased MSNA and attenuated increases in cardiac BRS and heart rate variability observed with regular training. These results support neural adaptations after overload training and suggest that increased central sympathetic outflow may be linked with decreased exercise performance. [ABSTRACT FROM AUTHOR]

Background: Lipopolysaccharide (LPS) induces acute inflammation, activates sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP), examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis. Methods: Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg). We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection. Results: In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.). In contrast, AP increased initially (until 75 min), then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP. Conclusions: LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed peripheral arc determines SNA and hemodynamics in LPS-induced acute inflammation. [ABSTRACT FROM AUTHOR]

The arterial baroreflex is a primary regulator of autonomic outflow to effectively regulate acute changes in blood pressure. After a spinal cord injury (SCI), regulation of autonomic function is disrupted, although the damage of the autonomic pathways may not necessarily be related to the severity of injury (i.e. level and completeness). Nonetheless, it can be assumed that there would be greater loss of sympathetic innervation with higher level of injury and that cardiac parasympathetic control would remain intact regardless of injury level. In those with SCI, impaired baroreflex regulation has implications not only for adequate pressure regulation, but also for long term cardiovascular health. In this review, we discuss the expected impact ofan SCI on baroreflex control and the studies that have investigated baroreflex sensitivity in this population. The data generally indicates that baroreflex sensitivity is lesser in those with chronic injuries. However, these findings are counter to the expected effect of an SCI and hence may indicate that the effect of an SCI on baroreflex control might be secondary to long term deconditioning and/or vascular stiffening of baroreceptive arteries. Furthermore, the alterations in the ability to regulate pressure do not impact the relationship between spontaneous heart rate and blood pressure variabilities. In addition, those with SCI are not adequately able to control blood pressure changes in response to orthostasis, resulting in frank hypotension in a significant proportion of those with high level injuries. [ABSTRACT FROM AUTHOR]

Physiological variables, such as heart rate (HR), blood pressure (BP) and respiration (RESP), are tightly regulated and coupled under healthy conditions, and a break-down in the coupling has been associated with aging and disease. We present an approach that incorporates physiological modeling within a switching linear dynamical systems (SLDS) framework to assess the various functional components of the autonomic regulation through transfer function analysis of nonstationary multivariate time series of vital signs. We validate our proposed SLDS-based transfer function analysis technique in automatically capturing 1) changes in baroreflex gain due to postural changes in a tilt-table study including ten subjects, and 2) the effect of aging on the autonomic control using HR/RESP recordings from 40 healthy adults. Next, using HR/BP time series of more than 450 adult ICU patients, we show that our technique can be used to reveal coupling changes associated with severe sepsis (AUC = 0.74, sensitivity = 0.74, specificity = 0.60). Our findings indicate that reduced HR/BP coupling is significantly associated with severe sepsis even after adjusting for clinical interventions (P $<=$ 0.001). These results demonstrate the utility of our approach in phenotyping complex vital-sign dynamics, and in providing mechanistic hypotheses in terms of break-down of autoregulatory systems under healthy and disease conditions. [ABSTRACT FROM AUTHOR]

Background: Carotid baroreflex activation lowers blood pressure and might have potential application for the treatment of resistant hypertension. We did a proof-of-principle trial with a novel endovascular baroreceptor amplification device, MobiusHD (Vascular Dynamics, Mountain View, CA, USA), in patients with resistant hypertension.Methods: CALM-FIM_EUR was a prospective, first-in-human, open-label study done at six European centres. Eligible patients were adults with resistant hypertension (office systolic blood pressure ≥160 mm Hg despite taking at least three antihypertensive agents, including a diuretic). MobiusHD devices were implanted unilaterally in the internal carotid artery. The primary endpoint was the incidence of serious adverse events at 6 months. Secondary endpoints included changes in office and 24 h ambulatory blood pressure. This trial is registered with ClinicalTrials.gov, number NCT01911897.Findings: Between December, 2013, and February, 2016, 30 patients were enrolled and underwent successful implantation. Mean age was 52 years (SD 12), 15 patients (50%) were men, and mean antihypertensive use was 4·4 drugs (1·4). Mean office blood pressure was 184/109 mm Hg (18/14) at baseline and was reduced by 24/12 mm Hg (13-34/6-18) at 6 months (p=0·0003 for systolic and p=0·0001 diastolic blood pressure). Mean baseline 24 h ambulatory blood pressure was 166/100 mm Hg (17/14) at baseline and was reduced by 21/12 mm Hg (14-29/7-16) at 6 months (p<0·0001 for systolic and diastolic blood pressure). Five serious adverse events had occurred in four patients (13%) at 6 months: hypotension (n=2), worsening hypertension (n=1), intermittent claudication (n=1) and wound infection (n=1).Interpretation: In patients with resistant hypertension, endovascular baroreceptor amplification with the MobiusHD device substantially lowered blood pressure with an acceptable safety profile. Randomised, double-blind, sham-controlled trials are warranted to investigate the use of this treatment further.Funding: Vascular Dynamics. [ABSTRACT FROM AUTHOR]

Objective: Caregiving stress is associated with increased risk of cardiovascular disease (CVD). Inability to adequately regulate blood pressure is a possible underlying mechanism explaining this risk. We examined the relationship between length of caregiving and cardiovagal baroreflex sensitivity (cBRS) to better understand the link between caregiving and CVD risk.Methods: A total of 146 elderly individuals (≥55years) participated in this study, of whom 96 were providing in-home care to a spouse with dementia and 50 were healthy controls married to a non-demented spouse (i.e., non-caregivers). Among the caregivers, 56 were short-term caregivers (caring<4years) and 40 were long-term caregivers (caring≥4years). A multiple linear regression model, with contrast codes comparing short and long-term caregivers with non-caregivers was used to understand relationships between chronic caregiving and cBRS.Results: After controlling for relevant demographic and health characteristics, mean±SE log transformed cBRS for non-caregivers was 0.971±0.029. Relative to non-caregivers, the long-term caregivers had significantly impaired cBRS (0.860±0.033; p=0.013). However, mean cBRS for short-term caregivers did not significant differ from non-caregivers (0.911±0.028; p=0.144).Conclusion: These results suggest that long-term caregiving stress is associated with an impaired cBRS. Accumulation of stress from years of caregiving could result in worse cBRS function, which could be a mechanistic explanation for the correlation between caregiving stress and the increased risk of CVD. [ABSTRACT FROM AUTHOR]

In 1968, the first reported microneurographic recordings of muscle sympathetic nerve activity (MSNA) in humans revealed the bursty behavior of efferent sympathetic nerve activity. The timing of bursts could be explained by baroreflex physiology, but the variability in size of each burst was left unexplained. On the basis of shorter latencies of larger bursts, Wallin's group [53] proposed the existence of variable supraspinal synaptic delays and/or options for recruitment of faster-conducting sympathetic neurons when bursts become stronger. These options represent features of recruitable neural systems. Based on the highly variable latencies of single axons whose firing patterns could not explain reflexive increases in burst size, the concept of a latent subpopulation of sympathetic axons was speculated to exist. Using evidence from experimental preparations in anesthetized smaller animals, to recent signal processing of multi-fiber recordings in humans, this brief review will discuss the attempts to discover and understand recruitment strategies within the peripheral sympathetic nervous system. The review focuses on new information from human recordings supporting the idea that rate coding, population coding (recruitment), and temporal coding are options available within the peripheral sympathetic nervous system to adjust efferent sympathetic outflow. Although data are limited, possible clinical applications are discussed. [ABSTRACT FROM AUTHOR]

The baroreflex is an important blood pressure regulating mechanism. The bed nucleus of stria terminalis ( BNST) modulates the baroreflex function. However, the local BNST neurochemical mechanisms involved in control of baroreflex responses are not completely understood. Therefore, in this study, we investigated the involvement of corticotropin-releasing factor ( CRF) receptors within the BNST in baroreflex control of heart rate in unanesthetized rats. For this, we evaluated effects of bilateral microinjection into the BNST of either the selective CRF1 receptor antagonist CP376395 (5 nmol/100 nL) or the selective CRF2 receptor antagonist antisauvagine-30 (5 nmol/100 nL) in bradycardiac response evoked by blood pressure increases caused by intravenous infusion of phenylephrine as well as tachycardiac response to blood pressure decrease caused by intravenous infusion of sodium nitroprusside. Bilateral microinjection of CP376395 into the BNST decreased the baroreflex bradycardiac response without affecting the reflex tachycardia. Conversely, BNST treatment with antisauvagine-30 decreased heart rate response during blood pressure drop without affecting the reflex bradycardia. Overall, these findings provide evidence of an involvement of CRF neurotransmission within the BNST in baroreflex activity. Nevertheless, data indicate that local CRF1 and CRF2 receptors differently modulate the baroreflex control of heart rate. [ABSTRACT FROM AUTHOR]

Purpose:The baroreflex is an important afferent mechanism controlling autonomic functions. As afferent nerves course through the neck, they are susceptible to damage by neck irradiation in head and neck cancer patients. With increased survival of head and neck cancer patients because of improved therapy, the cardiovascular morbidity and mortality in them have become apparent and this is of clinical concern. There are few case reports of baroreflex failure as a chronic sequel to neck irradiation. Objectives:The present study evaluated the changes in cardio-autonomic tone and postural cardiovascular reflex in neck-irradiated patients. Methods:Head and neck cancer patients who had received neck irradiation (n = 15) and healthy controls (n = 15) were evaluated for heart rate variability with time domain analysis of 5 min ECG recording. Postural cardiovascular reflexes were studied with changes in blood pressure and heart rate in the lying to standing test. Results:Our results suggest that there is a reduction in overall time domain measures of heart rate variability and weakened postural reflexes in neck-irradiated patients. Conclusion:Decreased heart rate variability in neck-irradiated patients reflects an independent risk of cardiovascular morbidity. The early detection of cardiovascular impairment in such patients may help healthcare professionals in providing better care. Furthermore, the dose delivered to the carotid sinus should be monitored and restricted. [ABSTRACT FROM AUTHOR]

Fibromyalgia syndrome (FMS) is a rheumatologic disorder characterized by chronic widespread pain, fatigue and other symptoms. Baroreflex dysfunction has been observed in women with FMS. However, it is unknown whether the limited involvement of the baroreflex control during an orthostatic stimulus has some impact on the quality of life of the FMS patient. Therefore, the aim of the study is evaluate the relationship between the quality of life of the FMS patient and indexes of the cardiovascular autonomic control as estimated from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP). We enrolled 35 women with FMS (age: 48.8±8.9 years; body mass index: 29.3±4.3 Kg/m2). The electrocardiogram, non-invasive finger blood pressure and respiratory activity were continuously recorded during 15 minutes at rest in supine position (REST) and in orthostatic position during active standing (STAND). Traditional cardiovascular autonomic control markers were assessed along with a Granger causality index assessing the strength of the causal relation from SAP to HP (CRSAP→HP) and measuring the degree of involvement of the cardiac baroreflex. The impact of FMS on quality of life was quantified by the fibromyalgia impact questionnaire (FIQ) and visual analog score for pain (VAS pain). No significant linear association was found between FIQ scores and the traditional cardiovascular indexes both at REST and during STAND (p>0.05). However, a negative relationship between CRSAP→HP during STAND and FIQ score was found (r = -0.56, p<0.01). Similar results were found with VAS pain. In conclusion, the lower the degree of cardiac baroreflex involvement during STAND in women with FMS, the higher the impact of FMS on the quality of life, thus suggesting that Granger causality analysis might be clinically helpful in assessing the state of the FMS patient. [ABSTRACT FROM AUTHOR]

Baroreflex-mediated changes in heart rate and vascular resistance in response to variations in blood pressure are critical to maintain homeostasis. We aimed to develop time domain analysis methods to complement existing cross-spectral techniques in the investigation of the vascular resistance baroreflex response to orthostatic stress. A secondary goal was to apply these methods to distinguish between levels of orthostatic tolerance using baseline data. Eleven healthy, normotensive males participated in a graded lower body negative pressure protocol. Within individual neurogenic baroreflex cycles, the amount of muscle sympathetic nerve activity (MSNA), the diastolic pressure stimulus and response amplitudes, diastolic pressure to MSNA burst stimulus and response times, as well as the stimulus and response slopes between diastolic pressure and MSNA were computed. Coherence, gain, and frequency of highest coherence between systolic/diastolic arterial pressure ( SAP/ DAP) and RR-interval time series were also computed. The number of MSNA bursts per low-frequency cycle increased from 2.55 ± 0.68 at baseline to 5.44 ± 1.56 at −40 mmHg of LBNP. Stimulus time decreased (3.21 ± 1.48-1.46 ± 0.43 sec), as did response time (3.47 ± 0.86-2.37 ± 0.27 sec). At baseline, DAP- RR coherence, DAP- RR gain, and the time delay between decreases in DAP and MSNA bursts were higher in participants who experienced symptoms of presyncope. Results clarified the role of different branches of the baroreflex loop, and suggested functional adaptation of neuronal pathways to orthostatic stress. [ABSTRACT FROM AUTHOR]

Background: Chronic low blood pressure (hypotension) is characterized by complaints such as fatigue, reduced drive, dizziness, and cold limbs. Additionally, deficits in attention and memory have been observed. Autonomic dysregulation is considered to be involved in the origin of this condition.Purpose: The study explored autonomic cardiovascular control in the context of higher cognitive processing (executive function) in hypotension.Methods: Hemodynamic recordings were performed in 40 hypotensive and 40 normotensive participants during execution of four classical executive function tasks (number-letter task, n-back task, continuous performance test, and flanker task). Parameters of cardiac sympathetic control, i.e., stroke volume, cardiac output, pre-ejection period, total peripheral resistance, and parasympathetic control, i.e., respiratory sinus arrhythmia and baroreflex sensitivity, were obtained.Results: The hypotensive group exhibited lower stroke volume and cardiac output, as well as higher pre-ejection period and baroreflex sensitivity during task execution. Increased error rates in hypotensive individuals were observed in the n-back and flanker tasks. In the total sample, there were positive correlations of error rates with pre-ejection period, baroreflex sensitivity and respiratory sinus arrhythmia, and negative correlations with cardiac output.Conclusions: Group differences in stroke volume, cardiac output, and pre-ejection period suggest diminished beta-adrenergic myocardial drive during executive function processing in hypotension, in addition to increased baroreflex function. Although further research is warranted to quantify the extent of executive function impairment in hypotension, the results from correlation analysis add evidence to the notion that higher sympathetic inotropic influences and reduced parasympathetic cardiac influences are accompanied by better cognitive performance. [ABSTRACT FROM AUTHOR]

Objective. Essential hypertension is associated with reduced pain sensitivity of unclear aetiology. This study explores this issue using the Cold Pressor Test (CPT), a reliable pain/stress model, comparing CPT-related EEG activity in first episode hypertensives and controls. Method. 22 untreated hypertensives and 18 matched normotensives underwent 24-hour ambulatory blood pressure monitoring (ABPM). EEG recordings were taken before, during, and after CPT exposure. Results. Significant group differences in CPT-induced EEG oscillations were covaried with the most robust cardiovascular differentiators by means of a Canonical Analysis. Positive correlations were noted between ABPM variables and Delta (1–4 Hz) oscillations during the tolerance phase; in high-alpha (10–12 Hz) oscillations during the stress unit and posttest phase; and in low-alpha (8–10 Hz) oscillations during CPT phases overall. Negative correlations were found between ABPM variables and Beta2 oscillations (16.5–20 Hz) during the posttest phase and Gamma (28.5–45 Hz) oscillations during the CPT phases overall. These relationships were localised at several sites across the cerebral hemispheres with predominance in the right hemisphere and left frontal lobe. Conclusions. These findings provide a starting point for increasing our understanding of the complex relationships between cerebral activation and cardiovascular functioning involved in regulating blood pressure changes. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the influence of exercise intensity on postexercise supine and tilt baroreflex sensitivity (BRS).Method: Nine healthy, active men performed 2 conditions of interval cycling of 40% maximal work rate (WRmax) and 75% WRmax of matched work done and a control condition of no exercise in a counterbalanced order. BRS outcome measures were determined at preexercise and postexercise up to +24 hr in supine and tilt positions. R-R interval and blood pressure data were collected over consecutive 10-min periods and were analyzed by Fast Fourier transformation analysis.Results: A fully repeated analysis of variance revealed a significant interaction (p < .05) between time and condition in supine for BRSαLF, F(3, 134) = 5.19, p < .05, ES = .39, and BRSTFTG, F(3, 134) = 5.65, p < .05, ES = .41, and in tilt for BRSUpUp, F(3, 134) = 3.54, p < .05, ES = .31, BRSDownDown, F(3, 134) = 5.94, p < .05, ES = .43, BRSαLF, F(4, 134) = 6.23, p < .05, ES = .44, and BRSTFTG, F(4, 134) = 9.22, p < .05, ES = .54. There were significant differences (p < .05) between condition comparisons at +15 min and between control and 75% WRmax and between the 40% WRmax and 75% WRmax conditions at +60 min. At +15 min, BRS was lower in the 75% WRmax condition compared with the 40% WRmax condition and the control condition, and it was lower in the 40% WRmax condition than in the control condition.Conclusion: The findings demonstrate an intensity-dependent relationship in the BRS response following exercise. [ABSTRACT FROM AUTHOR]

Objective: Physical complaints such as faintness, dizziness, cold limbs and headaches have been well-established in chronic low blood pressure (hypotension). This study investigated the occurrence of adverse emotional states and the symptoms of depression in this condition. As autonomic dysregulation, particularly diminished sympathetic tone, is believed to be involved in the etiology of hypotension, the impact of different facets of autonomic cardiovascular control on mood and depressive symptoms was also explored.Methods: Forty individuals with chronic hypotension and forty normotensive control persons were presented with the Mood Scale and Beck Depression Inventory. Stroke volume, cardiac output, pre-ejection period, Heather index and aortic peak blood flow velocity were recorded under resting conditions as indices of beta-adrenergic inotropic drive. Respiratory sinus arrhythmia and baroreflex sensitivity were additionally obtained.Results: Hypotensive individuals scored markedly higher on both questionnaire scales than controls, indicating an adversely affected emotional state and more severe depressive symptoms. In the entire sample, cardiac output, Heather index, and aortic peak blood flow velocity correlated negatively with the questionnaire scores; according to regression analysis, the Heather index explained the largest proportion of test score variance.Conclusion: Although hypotension does not constitute a serious medical condition, the findings of an adverse affective state and increased burden with depressive symptoms corroborate the view that it can have a considerable impact on wellbeing and quality of life. The correlations of the beta-adrenergic indices with the questionnaire scales indicate that cardiac sympathetic regulation plays a key role in the psychophysiological mediation of hypotension-related mood impairment. [ABSTRACT FROM AUTHOR]

Background: Sympathetic block in the upper limb has diagnostic, therapeutic and prognostic utility for disorders in the upper extremity that are associated with sympathetic disturbances. Increased skin temperature and decreased sweating are used to identify the adequacy of sympathetic block in the upper limb after stellate ganglion block (SGB). Baroreflexes elicited by postural change induce a reduction in peripheral blood flow by causing sympathetic vasoconstriction. We hypothesized that sympathetic block in the upper limb reduces the decrease in finger blood flow caused by baroreflexes stimulated by postural change from the supine to long sitting position. This study evaluated if sympathetic block of the upper limb affects the change in finger blood flow resulting from postural change. If change in finger blood flow would be kept against postural changes, it has a potential to be a new indicator of sympathetic blockade in the upper limb. Methods: Subjects were adult patients who had a check-up at the Department of Pain Management in our university hospital over 2 years and 9 months from May 2012. We executed a total of 91 SGBs in nine patients (N=9), which included those requiring treatment for pain associated with herpes zoster in seven of the patients, tinnitus in one patient and upper limb pain in one patient. We checked for the following four signs after performing SGB: Horner's sign, brachial nerve blockade, finger blood flow measured by a laser blood flow meter and skin temperature of the thumb measured by thermography, before and after SGB in the supine position and immediately after adopting the long sitting position. Results: We executed a total of 91 SGBs in nine patients. Two SGBs were excluded from the analysis due to the absence of Horner's sign. We divided 89 procedures into two groups according to elevation in skin temperature of the thumb: by over 1°C (sympathetic block group, n=62) and by <1°C (nonsympathetic block group, n=27). Finger blood flow decreased significantly just after a change in posture from the supine to long sitting position after SGB in both groups. In the sympathetic block group, the ratio of finger blood flow in the long sitting position/supine position with a change in posture significantly increased after SGB compared with before SGB (before SGB: range 0.09-0.94, median 0.53; after SGB: range 0.33-1.2, median 0.89, p<0.0001). Conclusion: Our study shows that with sympathetic block in the upper limb, the ratio of finger blood flow significantly increases despite baroreflexes stimulated by postural change from the supine to long sitting position. Retention of finger blood flow against postural changes may be an indicator of sympathetic block in the upper limb after SGB or brachial plexus block. [ABSTRACT FROM AUTHOR]

Background Paraganglioma is a rare neuroendocrine tumour arising anywhere along the paravertebral sympathetic and parasympathetic chains. In the neck, paraganglioma may affect the carotid body (carotid body tumour). Case report We describe a 43-year-old woman who presented with a reversible vasoconstriction syndrome associated with a posterior reversible encephalopathy syndrome following a surgery for a left carotid paraganglioma (with a past medical history of surgery for a right carotid paraganglioma a few months before). Conclusion A consequence of a baroreflex modification is discussed in order to explain the rare occurrence of such symptoms. [ABSTRACT FROM AUTHOR]

Researchers have investigated whether ultra-short-term (UST) heart rate variability values can replace traditional 5-minute values in clinical and optimal performance settings. Concurrent validity is the extent to which the results of a measurement correspond to a previously validated assessment of the same construct. Several studies either failed to specify their concurrent validity criteria or used an inappropriate statistical test. The authors proposed a rigorous standard and demonstrated that artifacted resting ultra-short-term heart rate variability values can achieve strong concurrent validity for diverse time-domain, frequency-domain, and nonlinear measurements in healthy undergraduates. Based on these findings, resting baselines as brief as 1 minute should be sufficient to measure heart rate, the standard deviation of the interbeat interval for normal beats (SDNN), and the square root of the mean squared difference of adjacent NN intervals (RMSSD) in clinical, optimal performance, and personal health assessment with individuals who resemble Truman State University undergraduates. [ABSTRACT FROM AUTHOR]

Key points Recent evidence indicates that metaboreflex regulates heart rate recovery after exercise (HRR)., An increased metaboreflex activity during the post-exercise period might help to explain the reduced HRR observed in hypertensive subjects., Using lower limb circulatory occlusion, the present study showed that metaboreflex activation during the post-exercise period delayed HRR in never-treated hypertensive men compared to normotensives., These findings may be relevant for understanding the physiological mechanisms associated with autonomic dysfunction in hypertensive men., Abstract Muscle metaboreflex influences heart rate (HR) regulation after aerobic exercise. Therefore, increased metaboreflex sensitivity may help to explain the delayed HR recovery (HRR) reported in hypertension. The present study assessed and compared the effect of metaboreflex activation after exercise on HRR, cardiac baroreflex sensitivity (cBRS) and heart rate variability (HRV) in normotensive (NT) and hypertensive (HT) men. Twenty-three never-treated HT and 25 NT men randomly underwent two-cycle ergometer exercise sessions (30 min, 70% [ABSTRACT FROM AUTHOR]

Contraction of freely perfused hind limb muscles in decerebrate rats evokes the exercise pressor reflex, resulting in sympathetic activation and increased blood pressure. This reflex is propagated along mechanically sensitive group III and metabolically sensitive group IV afferent nerve fibers. Recent research by our laboratory has focused on the exaggeration of the exercise pressor reflex in decerebrate rats with simulated peripheral artery disease, which was induced by ligating the femoral artery for 72 h before the start of the experiment. Recently, we showed that ligating the femoral artery increased the responses of single fiber group III and IV triceps surae muscle afferents to static contraction. The objective of this study was to determine if electrical stimulation of group III and IV afferents at frequencies approximating those occurring during static contraction was capable of reflexively increasing arterial blood pressure. We directly stimulated muscle afferents in the absence of muscle contraction for both freely perfused and ligated rats. We established 0.25 Hz as the minimal stimulation frequency to observe a sustained blood pressure response. The blood pressure response increased in a graded fashion as both stimulus frequency and motor threshold were increased. Additionally, we observed similar blood pressure responses from both freely perfused and ligated rats, suggesting that spinal and medullary processing of group III and IV afferent input plays no role in augmenting the pressor response to contraction caused by femoral artery ligation. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the effect of Premenstrual Syndrome (PMS) treatment with selective serotonin reuptake inhibitor (SSRI) on treatment response of refractory hypertension of the patients. Method: This was a triple-blind randomized clinical trial conducted on female patients suffering from refractory hypertension and PMS at the same time. We obtained informed consent from 40 patients who had inclusion criteria and selected 20 patients for the intervention (sertraline 50 mg daily) and 20 for the control groups. The study period was five weeks. The mean of systolic and diastolic blood pressure before and after intervention was measured separately for each individual in each group and the mean of blood pressure of the members of the two groups were compared with each other. Results: The mean age of the participants was 43.60 ± 4.57. In this study, systolic and diastolic blood pressure of both groups reduced after intervention. The mean of systolic blood pressure was reduced by 40.86 mmHg in the intervention group and this reduction was 16 mm Hg in control group after intervention (P<0.001). Comparing this reduction between the two groups, we found that reduction rate in systolic blood pressure of the two groups did not have a significant statistical difference before and after the intervention (P = 0.11). Mean of diastolic blood pressure also showed reduction of 9.17 mm Hg and that of control group showed 6.7-mmHg reduction. Reduction rate of diastolic blood pressure in the intervention group had a statistically significant difference with that of the control group (P<0.017). Conclusion: Administration of sertraline is more effective in controlling diastolic blood pressure in women suffering from refractory hypertension and comorbid PMS. [ABSTRACT FROM AUTHOR]

Background: Baroreflex dysfunction is a common feature of established cardiometabolic diseases that are most frequently associated with the development of critical illness. Laboratory models show that baroreflex dysfunction impairs cardiac contractility and cardiovascular performance, thereby increasing the risk of morbidity after trauma and sepsis. We hypothesized that baroreflex dysfunction contributes to excess postoperative morbidity after major surgery as a consequence of the inability to achieve adequate perioperative tissue oxygen delivery.Methods: In a randomized controlled trial of goal-directed haemodynamic therapy (GDT) in higher-risk surgical patients, baroreflex function was assessed using the spontaneous baroreflex sensitivity (BRS) method via an arterial line placed before surgery, using a validated sequence method technique (one beat lag). The BRS was calculated during the 6 h postoperative GDT intervention. Analyses of BRS were done by investigators blinded to clinical outcomes. The primary outcome was the association between postoperative baroreflex dysfunction (BRS <6 mm Hg s(-1), a negative prognostic threshold in cardiovascular pathology) and early postoperative morbidity. The relationship between baroreflex dysfunction and postoperative attainment of preoperative indexed oxygen delivery was also assessed.Results: Patients with postoperative baroreflex dysfunction were more likely to sustain infectious {relative risk (RR) 1.75 [95% confidence interval (CI): 1.07-2.85], P=0.02} and cardiovascular morbidity [RR 2.39 (95% CI: 1.22-4.71), P=0.008]. Prolonged hospital stay was more likely in patients with baroreflex dysfunction [unadjusted hazard ratio 1.62 (95% CI: 1.14-2.32), log-rank P=0.004]. Postoperative O2 delivery was 36% (95% CI: 7-65) lower in patients with baroreflex dysfunction in those not randomly assigned to GDT (P=0.02).Conclusions: Baroreflex dysfunction is associated with excess morbidity, impaired cardiovascular performance, and delayed hospital discharge, suggesting a mechanistic role for autonomic dysfunction in determining perioperative outcome.Clinical Trial Registration: ISCRTN76894700. [ABSTRACT FROM AUTHOR]

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure.Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys.Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation.Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation.

Background: Varenicline is an effective smoking cessation medication. Some concern has been raised that its use may precipitate adverse cardiovascular events although no patho-physiological mechanism potentially underlying such an effect has been reported. The aim of this study was to test the hypothesis that varenicline impacts on sympatho-vagal balance during smoking withdrawal. Methods: In this randomised, placebo-controlled trial, muscle sympathetic nerve activity (MSNA), baroreflex sensitivity (BRS), heart rate, and blood pressure were assessed in 17 smokers four weeks before a quit attempt (baseline) and again on the third day of that quit attempt (acute smoking withdrawal). Results: Regarding the primary endpoint of our study, we did not find a significant effect of varenicline compared to placebo on changes in MSNA burst incidence between baseline and acute smoking withdrawal (-3.0 ±3.3 vs.-3.9 ± 5.0 bursts/100 heart beats; p = 0.308). However, heart rate and systolic blood pressure significantly decreased in the placebo group only, while no significant changes in these parameters were observed in the varenicline group. Exposure to smoking cues during acute withdrawal lead to a significant increase of heart rate in the placebo group, while heart rate decreased in the varenicline group, and the difference in these changes was significant between groups (+2.7 ± 1.0 vs.-1.8±0.5 1/min;p = 0.002). In all 17 participants combined, a significant increase in heart rate during smoking cue exposure was detected in subjects who relapsed in the course of six weeks after the quit date compared to those who stayed abstinent (+2.5 ± 1.2 vs.--1.1 ± 0.7; p = 0.018). Six-week abstinence rates were higher in the varenicline group compared to placebo (88 vs. 22 %p = 0.015). Conclusion: We did not find evidence of adverse effects of varenicline on sympatho-vagal balance. Varenicline probably blunts the heart rate response to smoking cues, which may be linked to improved cessation outcome. [ABSTRACT FROM AUTHOR]

Introduction: Activation of the baroreflex system through the selective vagal nerve stimulation (sVNS) may become a treatment option for therapy-resistant hypertension, which is a frequently observed problem in the antihypertensive therapy. In previous studies, we used continuous sVNS to lower blood pressure (BP) without major side effects in a rat model. As continuous stimulation is energy consuming and sVNS could be implemented in an antihypertensive stimulator, it was the aim of this study to investigate the efficacy of pulsatile, cardiac-cycle-synchronized sVNS (cssVNS) on the reduction of BP.Methods: A multichannel cuff electrode was wrapped around the left vagal nerve in six male Wistar rats under Isoflurane anesthesia. BP was recorded in the left carotid artery. An electrocardiogram (ECG) was obtained via subcutaneous needle electrodes. The aortic depressor nerve fibers in the vagal nerve bundle were selectively stimulated with 18 parameter settings within a window of 15-30 ms after the R-peak in the ECG. The stimulation paradigm included every heartbeat, every second heart beat, and every third heart beat. BP and heart rate were initially recorded over 10 min.Results: Using cssVNS, BP could be significantly reduced over 30 min and maintained at this level. While the highest BP reduction was seen during cssVNS at every heartbeat with minimal bradycardia, less-yet significant-BP reduction was seen during cssVNS at every second or third heartbeat without causing detectable bradycardia.Conclusion: cssVNS can chronically reduce BP in rats avoiding measurable bradycardic side effects. This energy-efficient technique might allow the implementation of sVNS using an implantable device to permanently lower BP in patients.Funding: The study was funded by Bundesministerium fur Bildung und Forschung/German Federal Ministry of Education and Research among the call "Individualisierte Medizintechnik" under the grant number FKZ 13GW0120B. [ABSTRACT FROM AUTHOR]

We evaluated the effects of aerobic and resistance exercise training on ventricular morphometry and function, physical capacity, autonomic function, as well as on ventricular inflammatory status in trained rats prior to myocardial infarction. Male Wistar rats were divided into the following groups: sedentary+Sham, sedentary+ myocardial infarction, aerobic trained + myocardial infarction, and resistance trained + myocardial infarction. Sham and myocardial infarction were performed after training periods. In the days following the surgeries, evaluations were performed. Aerobic training prevents aerobic (to a greater extent) and resistance capacity impairments, ventricular dysfunction, baroreflex sensitivity and autonomic disorders (vagal tonus decrease and sympathetic tonus increase) triggered by myocardial infarction. Resistance training was able to prevent negative changes to aerobic and resistance capacity (to a greater extent) but not to ventricular dysfunction, and it prevented cardiovascular sympathetic increments. Additionally, both types of training reduced left ventricle inflammatory cytokine concentration. Our results suggest that aerobic and, for the first time, dynamic resistance training were able to reduce sympathetic tonus to the heart and vessels, as well as preventing the increase in pro-inflammatory cytokine concentrations in the left ventricle of trained groups. These data emphasizes the positive effects of aerobic and dynamic resistance training on the prevention of the negative changes triggered by myocardial infarction. [ABSTRACT FROM AUTHOR]

Purpose: High G tolerance is based on the capacity to maintain a sufficient level of arterial pressure (AP) during G load; therefore, we hypothesized that subjects with high G tolerance (H group) would have stronger arterial baroreflex responses compared to subjects with low G tolerance (L group). The carotid baroreflex was evaluated using the neck pressure method (NP), which assesses open-loop responses.Methods: The carotid baroreflex was tested in 16 subjects, n = 8 in the H and L group, respectively, in the supine and upright posture. Heart rate and AP were measured.Results: There were no differences between groups in the maximum slopes of the carotid baroreflex curves. However, the H group had a larger systolic and mean AP (SAP, MAP) increase to the initial hypotensive stimuli of the NP sequence in the upright position compared to the L group, 7.5 ± 6.6 vs 2.0 ± 2.4 and 4.1 ± 3.4 vs 1.1 ± 1.1 mmHg for SAP and MAP, respectively. Furthermore, the L group exhibited an increased latency between stimuli and response in AP in the upright compared to supine position, 4.1 ± 1.0 vs 3.1 ± 0.9 and 4.7 ± 1.1 vs 3.6 ± 0.9 s, for SAP and MAP. No differences in chronotropic responses were observed between the groups.Conclusions: It is concluded that the capacity for reflexive vasoconstriction and maintained speed of the vascular baroreflex during orthostatic stress are coupled to a higher relaxed GOR tolerance. [ABSTRACT FROM AUTHOR]

Background: The cold pressor test (CPT) is a recognized physiological technique to evaluate autonomic cardiovascular function. The present case study assessed the cardiovascular response of a healthy adult male during 3 min of CPT. Methods: Heart rate (HR) by single-lead electrocardiography and blood pressure (BP) by an arterial tonometer of the participant on a beat-to-beat basis were recorded before and during CPT. Results: HR during CPT showed a biphasic pattern with an initial increase from baseline (86 bpm) to the first 30 s of CPT (93 bpm) followed by a decrease. It dropped to 51 bpm during the last 30 s of CPT. Systolic blood pressure (SBP) increased from baseline (110 mmHg) to 1 min (122 mmHg) followed by a decrease. SBP immediately after CPT reduced to 57 mmHg. Diastolic blood pressure (DBP) from baseline (71 mmHg) slightly increased to 75 mmHg up to 90 s of the test, thereafter it registered a fall, and during the last 30 s of CPT, DBP fell to 30 mmHg. Stroke volume increased from baseline (75 mL/min) to the first 30 s (99 mL/min), followed by a slight reduction which was maintained till last of the test (70 mL/min). Cardiac output after an initial increase from baseline (6.4 L/min) to the first 30 s (9.2 L/min) decreased to 4.1 L/min during the last 30 s of the test. Baroreflex sensitivity (BRS) from baseline (9.32 ms/mmHg) plummeted to 6.67 ms/mmHg during the first 30 s of CPT followed by an increase, and after CPT, BRS was increased to 15.23 ms/mmHg. Other cardiovascular parameters such as myocardial contractility (dp/dt), total peripheral resistance, and mean arterial pressure were reduced in the individual at the time of loss of consciousness that occurred at the end of the last 30 s of CPT. Conclusions: The present case study described the modulation of cardiovascular functions of a healthy male during CPT, which finally led to the development of neurocardiogenic syncope characterized by hypotension and bradycardia. [ABSTRACT FROM AUTHOR]

Background: The hypertensive syndrome of Apparent Mineralocorticoid Excess is caused by loss-of-function mutations in the gene encoding 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), allowing inappropriate activation of the mineralocorticoid receptor by endogenous glucocorticoid. Hypertension is attributed to sodium retention in the distal nephron, but 11βHSD2 is also expressed in the brain. However, the central contribution to Apparent Mineralocorticoid Excess and other hypertensive states is often overlooked and is unresolved. We therefore used a Cre-Lox strategy to generate 11βHSD2 brain-specific knockout (Hsd11b2.BKO) mice, measuring blood pressure and salt appetite in adults.Methods and Results: Basal blood pressure, electrolytes, and circulating corticosteroids were unaffected in Hsd11b2.BKO mice. When offered saline to drink, Hsd11b2.BKO mice consumed 3 times more sodium than controls and became hypertensive. Salt appetite was inhibited by spironolactone. Control mice fed the same daily sodium intake remained normotensive, showing the intrinsic salt resistance of the background strain. Dexamethasone suppressed endogenous glucocorticoid and abolished the salt-induced blood pressure differential between genotypes. Salt sensitivity in Hsd11b2.BKO mice was not caused by impaired renal sodium excretion or volume expansion; pressor responses to phenylephrine were enhanced and baroreflexes impaired in these animals.Conclusions: Reduced 11βHSD2 activity in the brain does not intrinsically cause hypertension, but it promotes a hunger for salt and a transition from salt resistance to salt sensitivity. Our data suggest that 11βHSD2-positive neurons integrate salt appetite and the blood pressure response to dietary sodium through a mineralocorticoid receptor-dependent pathway. Therefore, central mineralocorticoid receptor antagonism could increase compliance to low-sodium regimens and help blood pressure management in cardiovascular disease. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? The cardiopulmonary baroreflex inhibits adjustment of sympathetic vasomotor outflow during mild-intensity dynamic exercise. However, it is unclear how suppression of sympathetic vasomotor outflow by the cardiopulmonary baroreflex is modulated by a powerful sympatho-excitatory drive from the exercise pressor reflex, central command and/or the arterial chemoreflex., What is the main finding and its importance? Hypoxia-induced heightened sympathetic nerve activity during dynamic exercise attenuated cardiopulmonary baroreflex control of sympathetic vasomotor outflow. This could facilitate the redistribution of blood flow to the active muscles by sympathetically mediated vasoconstriction of inactive muscles., Muscle sympathetic nerve activity (MSNA) does not increase during mild-intensity dynamic leg exercise in normoxic conditions, despite activation of central command and the exercise pressor reflex. Suppression of MSNA could be caused by muscle pump-induced loading of cardiopulmonary baroreceptors. In contrast, MSNA increases during mild dynamic leg exercise in hypoxic conditions. We hypothesized that hypoxic exercise, which induces a powerful sympatho-excitatory drive from the exercise pressor reflex, central command and/or arterial chemoreflex, attenuates cardiopulmonary reflex control of sympathetic vasomotor outflow. To test this hypothesis, MSNA was recorded during leg cycling in hypoxic conditions and with increased central blood volume by increasing the pedalling frequency to change the cardiopulmonary baroreflex. Subjects performed two leg cycle exercises at different pedal cadences of 60 and 80 r.p.m. (60EX and 80EX trials, respectively) in two (haemodynamic and MSNA) measurement conditions while breathing a hypoxic gas mixture (inspired oxygen fraction = 0.12). Thoracic impedance, stroke volume and cardiac output were measured non-invasively using impedance cardiography. During the MSNA test, MSNA was recorded via microneurography at the right median nerve at the elbow. Changes in thoracic impedance, stroke volume and cardiac output during the 80EX trial were greater than those during the 60EX trial. The MSNA burst frequency during hypoxic exercise in the 80EX trial (39 ± 4 bursts min−1) did not differ from that during the 60EX trial (39 ± 3 bursts min−1). These results suggest that the cardiopulmonary baroreflex of sympathetic vasomotor outflow during dynamic exercise is modulated by heightened hypoxia-induced sympathetic nerve activity. [ABSTRACT FROM AUTHOR]

High tolerance to progressive reductions in central blood volume has been associated with higher heart rate ( HR), peripheral vascular resistance ( PVR), sympathetic nerve activity ( SNA), and vagally mediated cardiac baroreflex sensitivity ( BRS). Using a database of 116 subjects classified as high tolerance to presyncopal-limited lower body negative pressure ( LBNP), we tested the hypothesis that subjects with greater cardiac baroreflex withdrawal (i.e., BRS > 1.0) would demonstrate greater LBNP tolerance associated with higher HR, PVR, and SNA. Subjects underwent LBNP to presyncope. Mean and diastolic arterial pressure ( MAP; DAP) was measured by finger photoplethysmography and BRS (down sequence) was autocalculated (Win CPRS) as ∆R-R Interval/∆ DAP. Down BRS (ms/mmHg) was used to dichotomize subjects into two groups (Group 1 = Down BRS > 1.0, N = 49, and Group 2 = Down BRS < 1.0, N = 67) at the time of presyncope. Muscle SNA was measured directly from the peroneal nerve via microneurography ( N = 19) in subjects from Groups 1 ( n = 9) and 2 ( n = 10). Group 1 (Down BRS > 1.0) had lower HR (107 ± 19 vs. 131 ± 20 bpm), higher stroke volume (45 ± 15 vs. 36 ± 15 mL), less SNA (45 ± 13 vs. 53 ± 7 bursts/min), and less increase in PVR (4.1 ± 1.3 vs. 4.5 ± 2.6) compared to Group 2 (Down BRS < 1.0). Both groups had similar tolerance times (1849 ± 260 vs. 1839 ± 253 sec), MAP (78 ± 11 vs. 79 ± 12 mmHg), compensatory reserve index ( CRI) (0.10 ± 0.03 vs. 0.09 ± 0.01), and cardiac output (4.5 ± 1.2 vs. 4.7 ± 1.1 L/min) at presyncope. Contrary to our hypothesis, higher HR, PVR, SNA, and BRS were not associated with greater tolerance to reduced central blood volume. These data are the first to demonstrate the variability and uniqueness of individual human physiological strategies designed to compensate for progressive reductions in central blood volume. The sum total of these integrated strategies is accurately reflected by the measurement of the compensatory reserve. [ABSTRACT FROM AUTHOR]

Background: Previous research indicated the complexity of autonomic dysfunction during acute alcohol withdrawal. This study aimed to investigate the pupillary light reflex as an indicator of midbrain and brainstem regulatory systems in relation to cardiovascular autonomic function.Methods: Thirty male patients were included in the study. They were investigated during acute alcohol withdrawal syndrome and 24h later during clomethiazole treatment and compared to healthy controls. Parameters of pupillary light reflex of both eyes as well as heart rate variability, blood pressure variability and baroreflex sensitivity (BRS) were studied.Results: We observed significantly reduced sympathetic (small diameter, e.g., left eye: 5.00 in patients vs. 5.91 mm in controls) and vagal modulation (e.g., prolonged latencies, left eye: 0.28 vs. 0.26 ms) regarding both pupils during acute alcohol withdrawal syndrome. Cardiovascular parameters showed reduced vagal modulation (e.g., b-slope of BRS: 7. 57 vs. 13.59 ms/mm Hg) and mixed results for sympathetic influence. After 24h, autonomic dysfunction improved significantly, both for the pupils (e.g., left diameter: 5.38 mm) and the heart (e.g., b-slope of BRS: 9.34 ms/mm Hg). While parameters obtained from the pupil correlated with cardiac autonomic function (e.g, BRS and left diameter: r=0.564) in healthy controls, no such pattern was observed in patients.Conclusion: Results obtained from the pupil during acute alcohol withdrawal do not simply mirror autonomic dysfunction regarding the heart. Pupillary and cardiovascular changes after 24h indicate state dependencies of the results. The findings are discussed with respect to autonomic mechanisms and potentially involved brain regions. [ABSTRACT FROM AUTHOR]

Blood pressure is a vital element to maintain circulation and eventually cellular respiration and metabolism. Blood pressure abnormalities are one of the most common diseases worldwide and their prevalence increases with age. For decades, basic and clinical investigations have shown that autonomic dysregulation/imbalance is involved in the development and progression of cardiovascular diseases. Arterial baroreflex is a powerful regulator of blood pressure and sympathetic nervous system. Closed-loop neuromodulation technology focusing on arterial baroreflex is challenging and might be promising to tackle the pathogenesis of blood pressure-related disorders, autonomic dysregulation, and eventually cardiovascular diseases. For more than a decade, we and associates have developed “bionic” baroreflex systems. “Bionic” means that the device is designed to replicate the dynamic characteristics of the native system to fully restore the function. The bionic baroreflex system basically consists of an artificial pressure sensor, a neurostimulator for autonomic nerves and a regulator that encodes blood pressure into neurostimulation. In the process of development toward clinical applicability, researchers have faced logical problems in designing the controller and practical problems of how to approach baroreflex activation. Closed-loop baroreflex systems utilizing sympathetic nerve trunk stimulation, spinal cord stimulation and noninvasive transcutaneous stimulation were proposed. Recently, the bionic baroreceptor was reported and proposed to be a potential therapy for heart failure. In this article, we introduce the closed-loop neuromodulation technology for baroreflex blood pressure control and discuss future direction of development of this technology. [ABSTRACT FROM AUTHOR]

Takotsubo cardiomyopathy (TC) often occurs after emotional or physical stress. Norepinephrine levels are unusually high in the acute phase, suggesting a hyperadrenergic mechanism. Comparatively little is known about parasympathetic function in patients with TC. We sought to characterize autonomic function at rest and in response to physical and emotional stimuli in 10 women with a confirmed history of TC and 10 age-matched healthy women. Sympathetic and parasympathetic activity was assessed at rest and during baroreflex stimulation (Valsalva maneuver and tilt testing), cognitive stimulation (Stroop test), and emotional stimulation (event recall, patients). Ambulatory blood pressure monitoring and measurement of brachial artery flow-mediated vasodilation were also performed. TC women (tested an average of 37 months after the event) had excessive pressor responses to cognitive stress (Stroop test: p <0.001 vs baseline and p = 0.03 vs controls) and emotional arousal (recall of TC event: p = 0.03 vs baseline). Pressor responses to hemodynamic stimuli were also amplified (Valsalva overshoot: p <0.05) and prolonged (duration: p <0.01) in the TC women compared with controls. Plasma catecholamine levels did not differ between TC women and controls. Indexes of parasympathetic (vagal) modulation of heart rate induced by respiration and cardiovagal baroreflex gain were significantly decreased in the TC women versus controls. In conclusion, even long after the initial episode, women with previous episode of TC have excessive sympathetic responsiveness and reduced parasympathetic modulation of heart rate. Impaired baroreflex control may therefore play a role in TC. [ABSTRACT FROM AUTHOR]

Background: Current-generation left ventricular assist devices provide circulatory support that is minimally or entirely nonpulsatile and are associated with marked increases in muscle sympathetic nerve activity (MSNA), likely through a baroreceptor-mediated pathway. We sought to determine whether the restoration of pulsatile flow through modulations in pump speed would reduce MSNA through the arterial baroreceptor reflex.Methods and Results: Ten men and 3 women (54 ± 14 years) with Heartmate II continuous-flow left ventricular assist devices underwent hemodynamic and sympathetic neural assessment. Beat-to-beat blood pressure, carotid ultrasonography at the level of the arterial baroreceptors, and MSNA via microneurography were continuously recorded to determine steady-state responses to step changes (200-400 revolutions per minute) in continuous-flow left ventricular assist device pump speed from a maximum of 10,480 ± 315 revolutions per minute to a minimum of 8500 ± 380 revolutions per minute. Reductions in pump speed led to increases in pulse pressure (high versus low speed: 17 ± 7 versus 26 ± 12 mm Hg; P<0.01), distension of the carotid artery, and carotid arterial wall tension (P<0.05 for all measures). In addition, MSNA was reduced (high versus low speed: 41 ± 15 versus 33 ± 16 bursts per minute; P<0.01) despite a reduction in mean arterial pressure and was inversely related to pulse pressure (P=0.037).Conclusions: Among subjects with continuous-flow left ventricular assist devices, the restoration of pulsatile flow through modulations in pump speed leads to increased distortion of the arterial baroreceptors with a subsequent decline in MSNA. Additional study is needed to determine whether reduction of MSNA in this setting leads to improved outcomes. [ABSTRACT FROM AUTHOR]

Background and Purpose: The ventral portion of the medial prefrontal cortex (vMPFC) comprises the infralimbic (IL), prelimbic (PL) and dorsopenducular (DP) cortices. The IL and PL regions facilitate the baroreceptor reflex arc. This facilitatory effect on the baroreflex is thought to be mediated by vMPFC glutamatergic transmission, through NMDA receptors. The glutamatergic transmission can be modulated by other neurotransmitters, such as the endocannabinoids, which are agonists of the TRPV1 receptor. TRPV1 channels facilitate glutamatergic transmission in the brain. Thus, we hypothesized that TRPV1 receptors in the vMPFC enhance the cardiac baroreflex response.Experimental Approach: Stainless steel guide cannulae were bilaterally implanted into the vMPFC of male Wistar rats. Afterwards, a catheter was inserted into the femoral artery, for recording MAP and HR, and into the femoral vein for assessing baroreflex activation.Key Results: Microinjections of the TRPV1 receptor antagonists capsazepine and 6-iodo-nordihydrocapsaicin (6-IODO) into the vMPFC reduced the cardiac baroreflex activity in unanaesthetized rats. Capsaicin microinjected into the vMPFC increased the cardiac baroreflex activity in unanaesthetized rats. When an ineffective dose of the TRPV1 receptor antagonist 6-IODO was used, the capsaicin-induced increase in the cardiac baroreflex response was abolished. The higher doses of capsaicin administered into the vMPFC after the ineffective dose of 6-IODO displaced the dose-response curve of the baroreflex parameters to the right, with no alteration in the maximum effect of capsaicin.Conclusions and Implications: The results of the present study show that stimulation of the TRPV1 receptors in the vMPFC increases the cardiac baroreceptor reflex response. [ABSTRACT FROM AUTHOR]

Aims: Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Carotid baroreceptor stimulation (baroreflex activation therapy, BAT) results in centrally mediated reduction of sympathetic and increase in parasympathetic activity. Because patients treated with cardiac resynchronization therapy (CRT) may have less sympathetic/parasympathetic imbalance, we hypothesized that there would be differences in the response to BAT in patients with CRT vs. those without CRT.Methods and Results: New York Heart Association (NYHA) Class III patients with an ejection fraction (EF) ≤35% were randomized (1 : 1) to ongoing guideline-directed medical and device therapy (GDMT, control) or ongoing GDMT plus BAT. Safety endpoint was system-/procedure-related major adverse neurological and cardiovascular events (MANCE). Efficacy endpoints were Minnesota Living with Heart Failure Quality of Life (QoL), 6-min hall walk distance (6MHWD), N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and HF hospitalization rate. In this sample, 146 patients were randomized (70 control; 76 BAT) and were 140 activated (45 with CRT and 95 without CRT). MANCE-free rate at 6 months was 100% in CRT and 96% in no-CRT group. At 6 months, in the no-CRT group, QoL score, 6MHWD, LVEF, NT-proBNP and HF hospitalizations were significantly improved in BAT patients compared with controls. Changes in efficacy endpoints in the CRT group favoured BAT; however, the improvements were less than in the no-CRT group and were not statistically different from control.Conclusions: BAT is safe and significantly improved QoL, exercise capacity, NTpro-BNP, EF, and rate of HF hospitalizations in GDMT-treated NYHA Class III HF patients. These effects were most pronounced in patients not treated with CRT. [ABSTRACT FROM AUTHOR]

Evidence derived from spontaneous measures of cardiovagal baroreflex sensitivity (BRS) suggests that slow breathing at 6 breaths/min augments BRS. However, increases in BRS associated with slow breathing may simply reflect the frequency-dependent nature of the baroreflex rather than the modulation of baroreflex function by changes in breathing rate per se. To test this hypothesis we employed a crossover study design (n = 14) wherein breathing rate and systolic arterial blood pressure (SAP) oscillation induced via the application of oscillating lower body negative pressure (OLBNP) were independently varied at fixed frequencies. Breathing rate was controlled at 6 or 10 breaths/min with the aid of a metronome, and SAP oscillations were driven at 0.06 Hz and 0.1 Hz using OLBNP. The magnitudes of SAP and R-R interval (cardiac period) oscillations were quantified using power spectral analysis, and the transfer function gain between SAP and R-R interval was used to estimate BRS. Linear mixed-effects models were used to examine the main effects and interactions between breathing rate and OLBNP frequency. There was no statistical interaction between breathing and OLBNP frequency (P = 0.59), indicating that the effect of breathing rate on BRS did not differ according to OLBNP frequency (and vice versa). Additionally, there was no main effect for breathing rate (P = 0.28). However, we observed a significant main effect for OLBNP frequency (P = 0.01) consistent with the frequency-dependent nature of baroreflex. These findings suggest that increases in spectral indices of BRS reflect the frequency dependence of the baroreflex and are not due to slow breathing per se. [ABSTRACT FROM AUTHOR]

Objective Baroreceptor stimulation yields antinociceptive effects. In this study, baroreceptors were stimulated by a respiratory maneuver, with the effect of this manipulation on pain perception subsequently measured. Methods Thirty-eight healthy participants were instructed to inhale slowly (control condition) and to hold the air in lungs after a deep inhalation (experimental condition). It was expected that breath-holding would increases blood pressure (BP) and thus stimulate the baroreceptors, which in turn would reduce pain perception. Pain was induced by pressure algometry on the nail of the left-index finger, at three different pressure intensities, and quantified by visual analogue scales. Heart rate (HR) and BP were continuously recorded. Results Pain perception was lower when pain pressure was administered during the breath-holding phase versus the slow inhalation phase, regardless of the pressure intensity. During breath-holding, a rapid increase in BP and decrease in HR were observed, demonstrating activation of the baroreceptor reflex. Conclusion Pain perception is reduced when painful stimulation is applied during breath-holding immediately following a deep inhalation. These results suggest that a simple and easy-to-perform respiratory maneuver could be used to reduce acute pain perception. [ABSTRACT FROM AUTHOR]