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STUDY OBJECTIVE: African Americans (AAs) show early signs of vascular dysfunction paired with elevated blood pressure (BP) and total peripheral resistance (TPR), which is thought to underlie their increased rates of cardiovascular health complications relative to European Americans (EAs). AAs paradoxically have higher cardiac vagal tone, indexed by heart rate variability (HRV), which is cardio-protective. This paradox has been termed the Cardiovascular Conundrum. The physiological mechanism underlying this phenomenon is not well understood. We examined race differences in baroreflex function, which might be an important mechanism underlying the Cardiovascular Conundrum. DESIGN: Participants completed a 5-minute baseline period where resting cardiac metrics were assessed. SETTING: Laboratory. PARTICIPANTS: 130 college-aged individuals (54 women, 57 AAs). MAIN OUTCOME MEASURES: Baroreflex function was indexed as baroreflex sensitivity (BRS; the magnitude of changes in cardiovascular activity in accordance with BP changes) and effectiveness (BEI; the ratio of BP changes that elicit changes in cardiovascular activity) in the cardiac, vascular, and myocardial limbs. RESULTS AND CONCLUSIONS: Results showed AAs to have higher HRV and cardiac BRS in comparison to EAs, suggesting the baroreflex is more sensitive to correcting the heart period for changes in BP among AAs compared to EAs. However, AAs showed lower vascular BEI relative to EAs, suggesting less effective control of TPR. In sum, lower BEI in the vascular branch might be an important mechanism underlying the Cardiovascular Conundrum (i.e., higher HRV and BP) and by extension, health disparities in cardiovascular diseases between AAs and EAs.

In this work, we couple a lumped‐parameter closed‐loop model of the cardiovascular system with a physiologically‐detailed mathematical description of the baroreflex afferent pathway. The model features a classical Hodgkin–Huxley current‐type model for the baroreflex afferent limb (primary neuron) and for the second‐order neuron in the central nervous system. The pulsatile arterial wall distension triggers a frequency‐modulated sequence of action potentials at the afferent neuron. This signal is then integrated at the brainstem neuron model. The efferent limb, representing the sympathetic and parasympathetic nervous system, is described as a transfer function acting on heart and blood vessel model parameters in order to control arterial pressure. Three in silico experiments are shown here: a step increase in the aortic pressure to evaluate the functionality of the reflex arch, a hemorrhagic episode and an infusion simulation. Through this model, it is possible to study the biophysical dynamics of the ionic currents proposed for the afferent limb components of the baroreflex during the cardiac cycle, and the way in which currents dynamics affect the cardiovascular function. Moreover, this system can be further developed to study in detail each baroreflex loop component, helping to unveil the mechanisms involved in the cardiovascular afferent information processing. [ABSTRACT FROM AUTHOR]

Surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) are options in severe aortic valve stenosis (AVS). Cardiovascular (CV) and cerebrovascular (CBV) control markers, derived from variability of heart period, systolic arterial pressure, mean cerebral blood velocity and mean arterial pressure, were acquired in 19 AVS patients (age: 76.8 ± 3.1 yrs, eight males) scheduled for SAVR and in 19 AVS patients (age: 79.9 + 6.5 yrs, 11 males) scheduled for TAVI before (PRE) and after intervention (POST, <7 days). Left ventricular function was preserved in both groups. Patients were studied at supine resting (REST) and during active standing (STAND). We found that: (i) both SAVR and TAVI groups featured a weak pre‐procedure CV control; (ii) TAVI ensured better CV control; (iii) cerebral autoregulation was working in PRE in both SAVR and TAVI groups; (iv) SAVR and TAVI had no impact on the CBV control; (v) regardless of group, CV and CBV control markers were not influenced by STAND in POST. Even though the post‐procedure preservation of both CV and CBV controls in TAVI group might lead to privilege this procedure in patients at higher risk, the missing response to STAND suggests that this advantage could be insignificant. [ABSTRACT FROM AUTHOR]

Harmattan is a season characterized by dust, cold, and sub-humid trade winds in Sub-Saharan countries. It’s similar to meteorological phenomena like Asian dust storms, Santa Ana winds, Australian bushfires, and Saharan dust in the Caribbean. It causes profound changes in the cardiorespiratory system in apparently healthy individuals and increases the risk of hospitalization in susceptible individuals. Exposure to these extreme conditions has been associated with alterations in autonomic function and baroreceptor sensitivity thus resulting in dysregulation of blood pressure control mechanisms. Baroreceptors are critical regulators of hemodynamics and cardiovascular function. They play a vital role in the short-term responses to blood pressure perturbation and are essential for acute restoration of blood pressure following cold exposure. Harmattan wind contains a barrage of chemicals, dust, and particulate matters depending on industrialization, natural and human activities. Particulate matter from Harmattan dust can trigger systemic inflammation and oxidative stress, exacerbating endothelial dysfunction and impairing vascular reactivity thus contributing to the pathogenesis of alterations in baroreceptor insensitivity, and cardiovascular diseases, including hypertension and atherosclerosis. Furthermore, fine particulate matter from dust may penetrate deep into the respiratory tract, activating pulmonary sensory receptors and eliciting reflex responses that influence autonomic tone. The presence of rich acrolein smokes and non-essential heavy metals such as cadmium, lead, and mercury in Harmattan wind also reduces baroreflex sensitivity, culminating in a sustained increase in diastolic and systolic blood pressure. This integrated review aims to provide valuable insights into how changes in each of these environmental constituents alter vital pathophysiologic and immunologic mechanisms of the body leading to baroreceptor instability and ultimately hemodynamic imbalance using available primary studies. Understanding this intricate interplay is crucial for implementing targeted interventions and informed public health strategies to mitigate the adverse effects of extreme environmental exposure and ultimately reduce poor health outcomes in the affected regions.

Background: Traditional pharmacological interventions are well tolerated in the management of elevated blood pressure (BP) for individuals with resistant hypertension. Although neuromodulation has been investigated as an alternative solution, its open-loop (OL) modality cannot follow the patient's physiological state. In fact, neuromodulation for controlling highly fluctuating BP necessitates a closed-loop (CL) stimulation modality based on biomarkers to monitor the patient's continuously varying physiological state. Objective: By leveraging its intuitive linkage with BP responses in ongoing efforts aimed at developing a CL system to enhance temporal BP reduction effect, this study proposes a CL neuromodulation modality that controls nucleus tractus solitarius (NTS) activity to effectively reduce BP, thus reflecting continuously varying physiological states. Method: While performing neurostimulation targeting the NTS in the rat model, the arterial BP response and neural activity of the NTS were simultaneously measured. To evaluate the temporal BP response effect of CL neurostimulation, OL (constant parameter; 20 Hz, 200 μA) and CL (Initial parameter; 11 Hz, 112 μA) stimulation protocols were performed with stimulation 180 s and rest 600 s, respectively, and examined NTS activity and BP response to the protocols. Results: In-vivo experiments for OL versus CL protocol for direct NTS stimulation in rats demonstrated an enhancement in temporal BP reduction via the CL modulation of NTS activity. Conclusion: This study proposes a CL stimulation modality that enhances the effectiveness of BP control using a feedback control algorithm based on neural signals, thereby suggesting a new approach to antihypertensive neuromodulation.

Introduction: Although terlipressin is known to cause bradycardia, this adverse effect is usually described in association with hypertension and is considered a benign compensatory response mediated by arterial baroreceptors. Cardiac monitoring for patients receiving terlipressin is not routinely recommended. Case Presentation: A 77-year-old female patient with no history of coronary artery disease and no other coexisting risk factors for cardiac arrhythmias or conduction disturbances was admitted to intensive care unit with severe cholangitis, complicated by variceal bleeding. She developed severe sinus bradycardia following the use of terlipressin, which was associated with significant hypotension that required the infusion of norepinephrine. The bradycardia occurred again when terlipressin therapy was reattempted. Conclusion: Vasopressin is known to sensitize baroreceptor reflexes by a central mechanism though its actions on V1a receptors in the area postrema, and we speculate that vasopressin analogues such as terlipressin may act in the same manner. That this effect is not widely described in terlipressin safety literature may be due to the overall younger age range of the trial population. This raises the possibility that cardiac monitoring may be warranted for elderly patients receiving terlipressin.

Abstract Background Obstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy. Methods and results Forty-one subjects with OSA had 25% higher plasma norepinephrine and 42% higher epinephrine measured every 2 h over 24 h than 20 control subjects. They also excreted more sodium during sleep. This suggested that that a sympatholytic would be a more successful antihypertensive than a diuretic. To test this hypothesis we treated a second group of 23 hypertensive apneics with placebo, 6 weeks of the sympatholytic guanfacine and 6 weeks of hydrochlorothiazide in a crossover study. Guanfacine lowered 24-hour blood pressure by 9.6/6.7 mmHg, more than the 5.4/2.9 mmHg effect of hydrochlorothiazide (P

Traditional pharmacological interventions are well tolerated in the management of elevated blood pressure (BP) for individuals with resistant hypertension. Although neuromodulation has been investigated as an alternative solution, its open-loop (OL) modality cannot follow the patient's physiological state. In fact, neuromodulation for controlling highly fluctuating BP necessitates a closed-loop (CL) stimulation modality based on biomarkers to monitor the patient's continuously varying physiological state. By leveraging its intuitive linkage with BP responses in ongoing efforts aimed at developing a CL system to enhance temporal BP reduction effect, this study proposes a CL neuromodulation modality that controls nucleus tractus solitarius (NTS) activity to effectively reduce BP, thus reflecting continuously varying physiological states. While performing neurostimulation targeting the NTS in the rat model, the arterial BP response and neural activity of the NTS were simultaneously measured. To evaluate the temporal BP response effect of CL neurostimulation, OL (constant parameter; 20 Hz, 200 μA) and CL (Initial parameter; 11 Hz, 112 μA) stimulation protocols were performed with stimulation 180 s and rest 600 s, respectively, and examined NTS activity and BP response to the protocols. In-vivo experiments for OL versus CL protocol for direct NTS stimulation in rats demonstrated an enhancement in temporal BP reduction via the CL modulation of NTS activity. This study proposes a CL stimulation modality that enhances the effectiveness of BP control using a feedback control algorithm based on neural signals, thereby suggesting a new approach to antihypertensive neuromodulation. • Real-time closed-loop brainstem modulation using NTS activity feedback enhances BP reduction. • BP response and NTS activity were analyzed with open-loop and closed-loop protocols. • Closed-loop protocol temporally enhanced stimulus-driven BP reduction compared to open-loop protocol. • Regulation of NTS activity increased temporal BP reduction. [ABSTRACT FROM AUTHOR]

Contemporary discussion of the baroreflex includes the efferent vascular-sympathetic and cardiovagal arms. Since sympathetic postganglionic neurons also innervate the left ventricle (LV), it is often assumed that the LV produces a sympathetically mediated increase in contractility during baroreceptor unloading, but this has not been characterized using a load-independent index of contractility. We aimed to determine 1) whether LV contractility increases in response to baroreceptor unloading and 2) whether such increases are mediated via the sympathetic or parasympathetic arm of the autonomic nervous system. Ten male Wistar rats were anesthetized (urethane) and instrumented with arterial and LV pressure-volume catheters to measure mean arterial pressure (MAP) and load-independent LV contractility [maximal rate of increase in pressure adjusted to end-diastolic volume (PAdP/dtmax)], respectively. Rats were placed in a servo-controlled lower-body negative pressure (LBNP) chamber to reduce MAP by 10% for 60 s to mechanically unload baroreceptors under control conditions. LBNP was repeated in each animal following infusions of cardiac autonomic blockers using esmolol (sympathetic), atropine (parasympathetic), and esmolol + atropine. Under control conditions, PAdP/dtmax increased during baroreceptor unloading (26 ± 6 vs. 31 ± 9 mmHg·s−1·μL−1, P = 0.031). During esmolol, there was no increase in LV contractility during baroreceptor unloading (11 ± 2 vs. 12 ± 2, P = 0.125); however, during atropine, there was an increase in LV contractility during baroreceptor unloading (26 ± 6 vs. 31 ± 9, P = 0.019). During combined esmolol and atropine, there was a small increase in contractility versus control (13 ± 3 vs. 15 ± 4, P = 0.046). Our results demonstrate that, in anesthetized rats, LV contractility increases in response to baroreceptor unloading, which is largely sympathetically mediated. NEW & NOTEWORTHY: This study empirically demonstrates a sympathetically mediated increase in LV contractility in response to baroreceptor unloading using a load-independent index of cardiac contractility in the anesthetized rat. [ABSTRACT FROM AUTHOR]

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]

Heart rate and vascular tension baroreflex exhibit resonance characteristics at approximately 0.1 and 0.03 Hz. In this study, we aimed to induce postural resonance (PR) through rhythmic postural adjustments. To assess the viability of this technique, we investigated the acute impacts of postural resonance on blood pressure, sympathetic nerve activity, and mood. Fifteen healthy study participants, consisting of 8 males and 7 females, were selected for this self-controlled study. Skin sympathetic nerve activity was continuously monitored during both the intervention and stress test on the experimental day. After PR intervention, the diastolic blood pressure and mean arterial pressure in the PR group exhibited significant reductions compared to the CON group (P = 0.032, CON = 71.67 ± 2.348, PR = 64.08 ± 2.35; P = 0.041, CON = 75.00 ± 2.17, PR = 81.67 ± 2.17). After PR intervention both left brachial ankle pulse wave velocity and right brachial ankle pulse wave velocity exhibited a significant reduction compared to pre-intervention levels (from 1115.86 ± 150.08 to 1048.43 ± 127.40 cm/s, p < 0.001; 1103.86 ± 144.35 to 1060.43 ± 121.35 cm/s, p = 0.018). PR intervention also led to a significant decrease in burst frequency and duration (P = 0.049; CON = 8.96 ± 1.17, PR = 5.51 ± 1.17) and a noteworthy decrease in burst amplitude and burst threshold during the cold-pressor test (P = 0.002; P = 0.002). Additionally, VAS scores exhibited a substantial increase following PR (P = 0.035, CON = 28.4 ± 4.49, PR = 42.17 ± 4.10). PR can induce resonance effects within the cardiovascular system, resulting in the effective reduction of blood pressure, skin sympathetic nerve activity and pulse wave velocity, and decreased burst amplitude and burst threshold of the sympathetic nerve during the cold-pressor test. [ABSTRACT FROM AUTHOR]

Self-organized criticality is a universal theory for dynamical systems that has recently been applied to the cardiovascular system. Precise methodological approaches are essential for understanding the dynamics of cardiovascular self-organized criticality. This study examines how the duration and quality of data recording affect the analysis of cardiovascular self-organized criticality, with a focus on the beat-by-beat heart rate variability time series obtained from seven healthy subjects in a standing position. Drawing a Zipf diagram, we evaluated the distribution of cardiovascular events of bradycardia and tachycardia. We identified tipping points for the distribution of both bradycardia and tachycardia events. By varying the recording durations (1, 2, 5, 10, 20, 30, and 40 min) and sampling frequencies (500, 250, and 100 Hz), we investigated their influence on the observed distributions. While shorter recordings can effectively capture cardiovascular events, they may underestimate the variables describing their distribution. Additionally, the tipping point of the Zipf distribution differs between bradycardia and tachycardia events. Comparisons of the distribution of bradycardia and tachycardia events should be conducted using long data recordings. Utilizing devices with lower sampling frequencies may compromise data fidelity. These insights contribute to refining experimental protocols and advancing our understanding of the complex dynamics underlying cardiovascular regulation. [ABSTRACT FROM AUTHOR]

Purpose: We examined heart rate variability (HRV) and baroreflex sensitivity (BRS) disease- and age-related response at 10-and 60-min after an acute high-intensity interval (HIIE) and moderate continuous exercise (MICE) in older adults with and without type 2 diabetes mellitus (T2DM) and healthy young adults. Methods: Twelve older male adults with (57–84 years) and without T2DM (57–76 years) and 12 healthy young male adults (20–40 years) completed an isocaloric acute bout of HIIE, MICE, and a non-exercise condition in a randomized order. Time and Wavelets-derived frequency domain indices of HRV and BRS were obtained in a supine position and offline over 2-min time-bins using Matlab. Results: HIIE but not MICE reduced natural logarithm root mean square of successive differences (Ln-RMSSD) (d = − 0.85; 95% CI − 1.15 to − 0.55 ms, p < 0.001), Ln-high-frequency power (d = − 1.60; 95% CI − 2.24 to − 0.97 ms2; p < 0.001), and BRS (d = − 6.32; 95% CI − 9.35 to − 3.29 ms/mmHg, p < 0.001) in adults without T2DM (averaged over young and older adults without T2DM), returning to baseline 60 min into recovery. These indices remained unchanged in older adults with T2DM after HIIE and MICE. Older adults with T2DM had lower resting Ln-RMSSD and BRS than aged-matched controls (Ln-RMSSD, d = − 0.71, 95% CI − 1.16 to − 0.262 ms, p = 0.001; BRS d = − 3.83 ms/mmHg), 95% CI − 6.90 to − 0.76, p = 0.01). Conclusions: Cardiovagal modulation following acute aerobic exercise is intensity-dependent only in adults without T2DM, and appears age-independent. These findings provide evidence of cardiac autonomic impairments in older adults with T2DM at rest and following aerobic exercise. [ABSTRACT FROM AUTHOR]

BACKGROUND An important prevalence (32%–45%) of masked hypertension has been reported in children with sickle cell disease (SCD). Stroke screening is well established using transcranial Doppler (TCD) ultrasound. The objectives of our proof-of-concept study in childhood SCD were to evaluate the prevalence of hypertension and its relationships with cerebral vasculopathy (TCD velocity) and to further evaluate in a subgroup of children the correlations of cardiovascular autonomic nervous system indices with TCD velocity. METHODS Ambulatory blood pressure measurement (ABPM) and TCD velocity were obtained in children with SCD and in a restricted sample, cardiac sympathovagal balance using heart rate variability analyses, baroreflex sensitivity, and pulse wave velocity were measured. RESULTS In 41 children with SCD (median age 14.0 years, 19 girls, SS/Sβ + thalassemia/SC: 33/2/6), ABPM results showed masked hypertension in 2/41 (5%, 95% confidence interval, 0–11) children, consistent with the prevalence in the general pediatric population, elevated blood pressure (BP) in 4/41 (10%) children, and a lack of a normal nocturnal dip in 19/41 children (46%). Children with increased TCD velocity had lower nocturnal dipping of systolic BP. In the 10 participants with extensive cardiovascular assessment, increased TCD velocity was associated with parasympathetic withdrawal and baroreflex failure. Exaggerated orthostatic pressor response or orthostatic hypertension was observed in 7/10 children that was linked to parasympathetic withdrawal. CONCLUSIONS Autonomic nervous system dysfunction, namely loss of parasympathetic modulation, of SCD contributes to increase TCD velocity but is not associated with an increased prevalence of masked hypertension. CLINICAL TRIALS REGISTRATION NCT04911049. [ABSTRACT FROM AUTHOR]

Abstract Surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) are options in severe aortic valve stenosis (AVS). Cardiovascular (CV) and cerebrovascular (CBV) control markers, derived from variability of heart period, systolic arterial pressure, mean cerebral blood velocity and mean arterial pressure, were acquired in 19 AVS patients (age: 76.8 ± 3.1 yrs, eight males) scheduled for SAVR and in 19 AVS patients (age: 79.9 + 6.5 yrs, 11 males) scheduled for TAVI before (PRE) and after intervention (POST,

This article presents the findings of a pilot trial on baroreflex activation therapy (BAT) for individuals with resistant hypertension (RH). RH refers to the inability to achieve a target blood pressure despite using multiple antihypertensive drugs. BAT involves using an implant to stimulate baroreceptors and lower blood pressure. The study found that BAT effectively reduced both ambulatory and home blood pressure in individuals with RH, with no serious adverse events reported. However, due to the small sample size, larger trials are needed to confirm these results. The article also provides information on hypertension, its prevalence, impact, risk factors, complications, and the importance of early detection and management. [Extracted from the article]

Abstract Background Subarachnoid hemorrhage (SAH) patients with cerebral autoregulation (CA) impairment at an early post-SAH period are at high risk of unfavorable outcomes due to delayed cerebral ischemia (DCI) or other complications. Limited evidence exists for an association between early-stage CA impairments and SAH patient outcomes. The objective of this prospective study was to explore associations between CA impairments detected in early post-SAH snapshot examinations and patient outcomes. Methods The pilot observational study included 29 SAH patients whose CA status was estimated 2–3 days after spontaneous aneurysm rupture and a control group of 15 healthy volunteers for comparison. Inflatable leg recovery boots (reboots.com, Germany) were used for the safe controlled generation of arterial blood pressure (ABP) changes necessary for reliable CA examination. At least 5 inflation‒deflation cycles of leg recovery boots with a 2–3 min period were used during examinations. CA status was assessed according to the delay time (∆TCBFV) measured between ABP(t) and cerebral blood flow velocity (CBFV(t)) signals during artificially induced ABP changes at boot deflation cycle. CBFV was measured in middle cerebral artery by using transcranial Doppler device. Results Statistically significant differences in ∆TCBFV were found between SAH patients with unfavorable outcomes (∆TCBFV = 1.37 ± 1.23 s) and those with favorable outcomes (∆TCBFV = 2.86 ± 0.99 s) (p

Background: Subarachnoid hemorrhage (SAH) patients with cerebral autoregulation (CA) impairment at an early post-SAH period are at high risk of unfavorable outcomes due to delayed cerebral ischemia (DCI) or other complications. Limited evidence exists for an association between early-stage CA impairments and SAH patient outcomes. The objective of this prospective study was to explore associations between CA impairments detected in early post-SAH snapshot examinations and patient outcomes. Methods: The pilot observational study included 29 SAH patients whose CA status was estimated 2–3 days after spontaneous aneurysm rupture and a control group of 15 healthy volunteers for comparison. Inflatable leg recovery boots (reboots.com, Germany) were used for the safe controlled generation of arterial blood pressure (ABP) changes necessary for reliable CA examination. At least 5 inflation‒deflation cycles of leg recovery boots with a 2–3 min period were used during examinations. CA status was assessed according to the delay time (∆TCBFV) measured between ABP(t) and cerebral blood flow velocity (CBFV(t)) signals during artificially induced ABP changes at boot deflation cycle. CBFV was measured in middle cerebral artery by using transcranial Doppler device. Results: Statistically significant differences in ∆TCBFV were found between SAH patients with unfavorable outcomes (∆TCBFV = 1.37 ± 1.23 s) and those with favorable outcomes (∆TCBFV = 2.86 ± 0.99 s) (p < 0.001). Early assessment of baroreflex sensitivity (BRS) during the deflation cycle showed statistically significant differences between the DCI and non-DCI patient groups (p = 0.039). Conclusions: A relatively small delay of ∆TCBFV <1.6 s between CBFV(t) and ABP(t) waves could be an early warning sign associated with unfavorable outcomes in SAH patients. The BRS during boot deflation can be used as a biomarker for the prediction of DCI. Trial registration: ClinicalTrials.gov Identifier: NCT06028906. Registered 31 August 2023 - Retrospectively registered, https://www.clinicaltrials.gov/study/NCT06028906. [ABSTRACT FROM AUTHOR]

Aims: Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long‐term safety and sustainable symptomatic improvement. Methods and results: BeAT‐HF was a prospective, multicentre, randomized, two‐arm, parallel‐group, open‐label, non‐implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT‐proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre‐specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6‐min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all‐cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow‐up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57–1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system‐ and procedure‐related major adverse neurological and cardiovascular event‐free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02–1.58) and freedom from all‐cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43–1.01) favoured the BAT group but did not reach statistical significance. Conclusion: The BeAT‐HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient's functional status, 6MHWD and QOL. [ABSTRACT FROM AUTHOR]

Background: We tested the hypothesis that patients with heart failure with preserved ejection fraction (HFpEF) would have greater muscle sympathetic nerve activity (MSNA) at rest and sympathetic reactivity during a cold pressor test compared with non–heart failure controls. Further, given the importance of the baroreflex modulation of MSNA in the control of blood pressure (BP), we hypothesized that patients with HFpEF would exhibit a reduced sympathetic baroreflex sensitivity. METHODS: Twenty-eight patients with HFpEF and 44 matched controls (mean±SD: 71±8 versus 70±7 years; 9 men/19 women versus 16 men/28 women) were studied. BP, heart rate, and MSNA (microneurography) were measured during 6 to 10 minutes of supine rest and the 2-minute cold pressor test. Spontaneous sympathetic baroreflex sensitivity was assessed during supine rest. Results: Patients with HFpEF had higher resting MSNA burst frequency (39±14 versus 31±12 bursts/min; P =0.020) and lower sympathetic baroreflex sensitivity (−2.83±0.76 versus −3.57±1.19 bursts/100 heartbeats/mm Hg; P =0.019) than controls, but burst incidence was not different between groups (56±19 versus 50±20 bursts/100 heartbeats; P =0.179). During the cold pressor test, increases in MSNA indices did not differ between groups (P =0.135–0.998), but patients had a smaller increase in diastolic BP (Δ4±6 versus Δ14±11 mm Hg; P <0.001) compared with controls. Conclusions: Despite augmented resting MSNA burst frequency, burst incidence was not significantly different between groups, and sympathetic baroreflex sensitivity was reduced in patients with HFpEF. Furthermore, patients had preserved sympathetic reactivity but attenuated diastolic BP responses during the cold pressor test. These data suggest that, during physiological stress, sympathetic reactivity is intact, but the peripheral pathway for sympathetic vasoconstriction may be impaired in HFpEF. [ABSTRACT FROM AUTHOR]

The ability to increase cardiac output during dynamic exercise is paramount for the ability to maintain workload performance. Reflex control of the cardiovascular system during exercise is complex and multifaceted involving multiple feedforward and feedback systems. One major reflex thought to mediate the autonomic adjustments to exercise is termed the muscle metaboreflex and is activated via afferent neurons within active skeletal muscle which respond to the accumulation of interstitial metabolites during exercise when blood flow and O2 delivery are insufficient to meet metabolic demands. This is one of the most powerful cardiovascular reflexes capable of eliciting profound increases in sympathetic nerve activity, arterial blood pressure, central blood volume mobilization, heart rate and cardiac output. This review summarizes the mechanisms meditating muscle metaboreflex‐induced increases in cardiac output. Although much has been learned from studies using anaesthetized and/or decerebrate animals, we focus on studies in conscious animals and humans performing volitional exercise. We discuss the separate and interrelated roles of heart rate, ventricular contractility, ventricular preload and ventricular–vascular coupling as well as the interaction with other cardiovascular reflexes which modify muscle metaboreflex control of cardiac output. We discuss how these mechanisms may be altered in subjects with heart failure with reduced ejection fraction and offer suggestions for future studies. [ABSTRACT FROM AUTHOR]

Discharge of postganglionic muscle sympathetic nerve activity (MSNA) is related poorly to blood pressure (BP) in adults. Whether neural measurements beyond the prevailing level of MSNA can account for interindividual differences in BP remains unclear. The current study sought to evaluate the relative contributions of sympathetic-BP transduction and sympathetic barore- flex gain on resting BP in young adults. Data were analyzed from 191 (77 females) young adults (18-39 years) who underwent continuous measurement of beat-to-beat BP (finger photoplethysmography), heart rate (electrocardiography), and fibular nerve MSNA (microneurography). Linear regression analyses were computed to determine associations between sympathetic-BP transduction (signal-averaging) or sympathetic baroreflex gain (threshold technique) and resting BP, before and after controlling for age, body mass index, and MSNA burst frequency. K-mean clustering was used to explore sympathetic phenotypes of BP control and consequential influence on resting BP. Sympathetic-BP transduction was unrelated to BP in males or females (both R² < 0.01; P > 0.67). Sympathetic baroreflex gain was positively associated with BP in males (R² = 0.09, P < 0.01), but not in females (R² < 0.01; P = 0.80), before and after controlling for age, body mass index, and MSNA burst frequency. K-means clustering identified a subset of participants with average resting MSNA, yet lower sympathetic-BP transduction and lower sympathetic baroreflex gain. This distinct subgroup presented with elevated BP in males (P < 0.02), but not in females (P = 0.10). Sympathetic-BP transduction is unrelated to resting BP, while the association between sympathetic baroreflex gain and resting BP in males reveals important sex differences in the sympathetic determination of resting BP. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is associated with autonomic dysregulation, which may be related to baroreflex dysfunction. Thus, we tested the hypothesis that cardiac and peripheral vascular responses to baroreflex activation via lower-body negative pressure (LBNP; -10, -20, -30, -40 mmHg) would be diminished in patients with HFpEF (n = 10, 71 ± 7 yr) compared with healthy controls (CON, n = 9, 69 ± 5 yr). Changes in heart rate (HR), mean arterial pressure (MAP, Finapres), forearm blood flow (FBF, ultrasound Doppler), and thoracic impedance (Z) were determined. Mild levels of LBNP (-10 and -20 mmHg) were used to specifically assess the cardiopulmonary baroreflex, whereas responses across the greater levels of LBNP represented an integrated baroreflex response. LBNP significantly increased in HR in CON subjects at -30 and -40 mmHg (þ3 ± 3 and þ6 ± 5 beats/min, P < 0.01), but was unchanged in patients with HFpEF across all LBNP levels. LBNP provoked progressive peripheral vasoconstriction, as quantified by changes in forearm vascular conductance (FVC), in both groups. However, a marked (40%-60%) attenuation in FVC responses was observed in patients with HFpEF (-6±8, -15 ± 6, -16 ± 5, and -19 ± 7 mL/min/mmHg at -10, -20, -30, and -40 mmHg, respectively) compared with controls (-15 ± 10, -22 ± 6, -25 ± 10, and -28 ± 10 mL/min/mmHg, P < 0.01). MAP was unchanged in both groups. Together, these data provide new evidence for impairments in cardiopulmonary baroreflex function and diminished cardiovascular responsiveness during hypovolemia in patients with HFpEF, which may be an important aspect of the disease-related changes in autonomic cardiovascular control in this patient group. [ABSTRACT FROM AUTHOR]

Cardiovascular homeostasis is maintained, in part, by neural signals arising from arterial baroreceptors that apprise the brain of blood volume and pressure. Here, we test whether neurons within the nodose ganglia that express angiotensin type-1a receptors (referred to as NGAT1aR) serve as baroreceptors that differentially influence blood pressure (BP) in male and female mice. Using Agtr1a-Cre mice and Cre-dependent AAVs to direct tdTomato to NGAT1aR, neuroanatomical studies revealed that NGAT1aR receive input from the aortic arch, project to the caudal nucleus of the solitary tract (NTS), and synthesize mechanosensitive ion channels, Piezo1/2. To evaluate the functionality of NGAT1aR, we directed the fluorescent calcium indicator (GCaMP6s) or the light-sensitive channelrhodopsin-2 (ChR2) to Agtr1a-containing neurons. Two-photon intravital imaging in Agtr1a-GCaMP6s mice revealed that NGAT1aR couple their firing to elevated BP, induced by phenylephrine (i.v.). Furthermore, optical excitation of NGAT1aR at their soma or axon terminals within the caudal NTS of Agtr1a-ChR2 mice elicited robust frequency-dependent decreases in BP and heart rate, indicating that NGAT1aR are sufficient to elicit appropriate compensatory responses to vascular mechanosensation. Optical excitation also elicited hypotensive and bradycardic responses in ChR2-expressing mice that were subjected to deoxycorticosterone acetate (DOCA)-salt hypertension; however, the duration of these effects was altered, suggestive of hypertension-induced impairment of the baroreflex. Similarly, increased GCaMP6s fluorescence observed after administration of phenylephrine was delayed in mice subjected to DOCA-salt or chronic delivery of angiotensin II. Collectively, these results reveal the structure and function of NGAT1aR and suggest that such neurons may be exploited to discern and relieve hypertension. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) describes a set of disorders that collectively influence cardiovascular health, and includes hypertension, obesity, insulin resistance, diabetes, and dyslipidemia. All these components (hypertension, obesity, dyslipidemia, and prediabetes/diabetes) have been shown to modify autonomic function. The major autonomic dysfunction that has been documented with each of these components is in the control of sympathetic outflow to the heart and periphery at rest and during exercise through modulation of the arterial baroreflex and the muscle metaboreflex. Many studies have described MetS components in singularity or in combination with the other major components of metabolic syndrome. However, many studies lack the capability to study all the factors of metabolic syndrome in one model or have not focused on studying the effects of how each component as it arises influences overall autonomic function. The goal of this review is to describe the current understanding of major aspects of metabolic syndrome that most likely contribute to the consequent/associated autonomic alterations during exercise and discuss their effects, as well as bring light to alternative mechanisms of study. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the effect of levodopa on postural blood pressure changes in individuals with Parkinson disease (PD) with (PD+OH) and without neurogenic OH (PD−OH). Methods: We performed a prospective randomized crossover study with autonomic testing performed ON and OFF levodopa. The primary outcome was the change in systolic blood pressure (SBP) from supine to 70° tilt at 3 min (ΔSBP-3'). Secondary outcomes included indices of baroreflex function and blood pressure and heart rate during tilt. Results: We enrolled 40 individuals with PD (21 PD+OH, 19 PD−OH), mean age (SD) 73.2 years (7.9), 13 women (32.5%)). There was no difference in age, sex, disease duration, and severity between PD+OH and PD−OH. Mean difference in ΔSBP-3' ON versus OFF levodopa in the whole study population was − 3.20 mmHg [− 7.36 to 0.96] (p = 0.14). Mean difference in ΔSBP-3' was − 2.14 mmHg [− 7.55 to 3.28] (p = 0.45) in PD+OH and − 5.14 mmHg [− 11.63 to 1.35] (p = 0.14) in PD−OH. Mean difference in ΔSBP ON versus OFF levodopa was greater at 7 and 10 min (− 7.52 mmHg [− 11.89 to − 3.15], p = 0.002, and − 7.82 mmHg [− 14.02 to − 1.67], p = 0.02 respectively). Levodopa was associated with lower absolute values of blood pressure in both PD+OH and PD−OH and cardiovascular noradrenergic baroreflex impairment. Conclusion: Levodopa decreases blood pressure in both PD with and without autonomic failure, but it does not cause a greater fall in blood pressure from supine to standing at 3 min. Levodopa-induced baroreflex sympathetic noradrenergic impairment may contribute to lower blood pressure. Lower standing blood pressure with levodopa may increase the risks of fall and syncope. [ABSTRACT FROM AUTHOR]

Purpose: Orthostasis increases the variability of continuously recorded blood pressure (BP). Low-frequency (LF) BP oscillations (Mayer waves) in this setting are related to the vascular-sympathetic baroreflex. Mechanisms of increased high-frequency (HF) BP oscillations at the periodicity of respiration during orthostasis have received less research attention. A previously reported patient with post-neurosurgical orthostatic hypotension (OH) and vascular-sympathetic baroreflex failure had large tilt-evoked, breathing-driven BP oscillations, suggesting that such oscillations can occur independently of vascular-sympathetic baroreflex modulation. In the present study we assessed effects of orthostasis on BP variability in the frequency domain in patient cohorts with or without OH. Methods: Power spectral analysis of systolic BP variability was conducted on recordings from 73 research participants, 42 with neurogenic OH [13 pure autonomic failure, 14 Parkinson's disease (PD) with OH, 12 parkinsonian multiple system atrophy, and 3 status post-brainstem neurosurgery] and 31 without OH (control group of 16 healthy volunteers and 15 patients with PD lacking OH), before, during, and after 5′ of head-up tilt at 90 degrees from horizontal. The data were log transformed for statistical testing. Results: Across all subjects, head-up tilting increased HF power of systolic BP variability (p = 0.001), without a difference between the neurogenic OH and control groups. LF power during orthostasis was higher in the control than in the OH groups (p = 0.009). Conclusions: The results of this observational cohort study confirm those based on our case report and lead us to propose that even in the setting of vascular-sympathetic baroreflex failure orthostasis increases HF power of BP variability. [ABSTRACT FROM AUTHOR]

Study objective: African Americans (AAs) show early signs of vascular dysfunction paired with elevated blood pressure (BP) and total peripheral resistance (TPR), which is thought to underlie their increased rates of cardiovascular health complications relative to European Americans (EAs). AAs paradoxically have higher cardiac vagal tone, indexed by heart rate variability (HRV), which is cardio-protective. This paradox has been termed the Cardiovascular Conundrum. The physiological mechanism underlying this phenomenon is not well understood. We examined race differences in baroreflex function, which might be an important mechanism underlying the Cardiovascular Conundrum. Design: Participants completed a 5-minute baseline period where resting cardiac metrics were assessed. Setting: Laboratory. Participants: 130 college-aged individuals (54 women, 57 AAs). Main outcome measures: Baroreflex function was indexed as baroreflex sensitivity (BRS; the magnitude of changes in cardiovascular activity in accordance with BP changes) and effectiveness (BEI; the ratio of BP changes that elicit changes in cardiovascular activity) in the cardiac, vascular, and myocardial limbs. Results and conclusions: Results showed AAs to have higher HRV and cardiac BRS in comparison to EAs, suggesting the baroreflex is more sensitive to correcting the heart period for changes in BP among AAs compared to EAs. However, AAs showed lower vascular BEI relative to EAs, suggesting less effective control of TPR. In sum, lower BEI in the vascular branch might be an important mechanism underlying the Cardiovascular Conundrum (i.e., higher HRV and BP) and by extension, health disparities in cardiovascular diseases between AAs and EAs.

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.

Background: Heart rate variability (HRV) modulates both the sympathetic nervous system and the parasympathetic nervous system (PNS) of the autonomic nervous system. Mood disorder is one of the contributing factors to influence HRV. The warm-water footbath as a relaxing way is used to enhance the PNS. In this study, we intended to explore the association between HRV and a footbath in the mood disorder group. Methods: We recruited 14 young male study participants to receive a 30-minute warm-water footbath three times a week. Furthermore, we monitored the heart rates electrocardiographically before, during, and after the intervention. Results: This study showed that the footbath not only significantly enhanced standard deviation of NN (SDNN) intervals, high-frequency (HF) power, and low-frequency (LF) power during the first five minutes footbath (p < 0.01) but also increased all the parameters in five minutes after finishing the footbath. SDNN intervals, HF power, and LF power remained significantly upward in the next five minutes (p < 0.05). Conclusion: In line with previous studies, this study showed that a footbath elevated the PNS-related HRV parameters. We suggest that a warm-water footbath improves the PNS modulation possibly through baroreflex. In addition, those with cardiac conditions and depression should be particularly attentive to their condition during and following a footbath.

Introduction: Simultaneous beat-to-beat R-R intervals, blood pressure and respiration signals are routinely analyzed for the evaluation of autonomic cardiovascular and cardiorespiratory regulations for research or clinical purposes. The more recognized analyses are i) heart rate variability and cardiac coherence, which provides an evaluation of autonomic nervous system activity and more particularly parasympathetic and sympathetic autonomic arms; ii) blood pressure variability which is mainly linked to sympathetic modulation and myogenic vascular function; iii) baroreflex sensitivity; iv) time-frequency analyses to identify fast modifications of autonomic activity; and more recently, v) time and frequency domain Granger causality analyses were introduced for assessing bidirectional causal links between each considered signal, thus allowing the scrutiny of many physiological regulatory mechanisms. Methods: These analyses are commonly applied in various populations and conditions, including mortality and morbidity predictions, cardiac and respiratory rehabilitation, training and overtraining, diabetes, autonomic status of newborns, anesthesia, or neurophysiological studies. Results: We developed CVRanalysis, a free software to analyze cardiac, vascular and respiratory interactions, with a friendly graphical interface designed to meet laboratory requirements. The main strength of CVRanalysis resides in its wide scope of applications: recordings can arise from beat-to-beat preprocessed data (R-R, systolic, diastolic and mean blood pressure, respiration) or raw data (ECG, continuous blood pressure and respiratory waveforms). It has several tools for beat detection and correction, as well as setting of specific areas or events. In addition to the wide possibility of analyses cited above, the interface is also designed for easy study of large cohorts, including batch mode signal processing to avoid running repetitive operations. Results are displayed as figures or saved in text files that are easily employable in statistical softwares. Conclusion: CVRanalysis is freely available at this website: anslabtools.univ-st-etienne.fr. It has been developed using MATLAB® and works on Windows 64-bit operating systems. The software is a standalone application avoiding to have programming skills and to install MATLAB. The aims of this paper area are to describe the physiological, research and clinical contexts of CVRanalysis, to introduce the methodological approach of the different techniques used, and to show an overview of the software with the aid of screenshots. [ABSTRACT FROM AUTHOR]

The ratio of low-frequency (LF, ~0.1 Hz) waves of RR interval duration (RRI) and systolic blood pressure (SAP) reflects the cardiac baroreflex sensitivity (BRS). Gravitational unloading (GU) may alter BRS during head-up tilt test (HUT) and lower body negative pressure (LBNP) test. Both effects cause blood redistribution to the lower body, but HUT is accompanied by greater unloading of sinocarotid baroreceptors than LBNP and activation of the vestibulosympathetic reflex. However, GU effects on BRS in these tests have not been directly compared previously. In this study we tested the hypothesis that the effect of dry immersion (DI, on-ground model of GU) on BRS in the same subjects will be more pronounced during HUT than during LBNP, while causing a comparable decrease in stroke volume (SV). Nine healthy men participated in two test sessions (before and after 7-day DI) consisting of five 3-min HUT (65°C) and five 3-min LBNP (–35 mmHg) with data averaging in each test. Wavelet analysis was used to determine the amplitude of the RRI and SAP waves in the 0.05–0.13 Hz range. The amplitude of LF waves of SAP increased in both tests, after DI—more significantly in HUT. The amplitude of LF RRI waves decreased in two tests; the percentage decrease did not differ between tests and did not change under the influence of DI. The α-coefficient (the ratio of RRI and SAP LF wave amplitudes) decreased equally in two tests before DI. After DI, more pronounced α-coefficient reduction was observed in HUT test but not in LBNP test. Thus, the effect of DI on BRS is evident in HUT, but not in LBNP, which may be explained by the more pronounced influence of HUT on the mechanisms of neural control of heart rhythm. [ABSTRACT FROM AUTHOR]

Introduction: Although terlipressin is known to cause bradycardia, this adverse effect is usually described in association with hypertension and is considered a benign compensatory response mediated by arterial baroreceptors. Cardiac monitoring for patients receiving terlipressin is not routinely recommended. Case Presentation: A 77-year-old female patient with no history of coronary artery disease and no other coexisting risk factors for cardiac arrhythmias or conduction disturbances was admitted to intensive care unit with severe cholangitis, complicated by variceal bleeding. She developed severe sinus bradycardia following the use of terlipressin, which was associated with significant hypotension that required the infusion of norepinephrine. The bradycardia occurred again when terlipressin therapy was reattempted. Conclusion: Vasopressin is known to sensitize baroreceptor reflexes by a central mechanism though its actions on V1a receptors in the area postrema, and we speculate that vasopressin analogues such as terlipressin may act in the same manner. That this effect is not widely described in terlipressin safety literature may be due to the overall younger age range of the trial population. This raises the possibility that cardiac monitoring may be warranted for elderly patients receiving terlipressin. [ABSTRACT FROM AUTHOR]

Premature birth may result in specific cardiovascular responses to hypoxia and hypercapnia, that might hamper high‐altitude acclimatization. This study investigated the consequences of premature birth on baroreflex sensitivity (BRS) under hypoxic, hypobaric and hypercapnic conditions. Seventeen preterm born males (gestational age, 29 ± 1 weeks), and 17 age‐matched term born adults (40 ± 0 weeks) underwent consecutive 6‐min stages breathing different oxygen and carbon dioxide concentrations at both sea‐level and high‐altitude (3375 m). Continuous blood pressure and ventilatory parameters were recorded in normobaric normoxia (NNx), normobaric normoxic hypercapnia (NNx + CO2), hypobaric hypoxia (HHx), hypobaric normoxia (HNx), hypobaric normoxia hypercapnia (HNx + CO2), and hypobaric hypoxia with end‐tidal CO2 clamped at NNx value (HHx + clamp). BRS was assessed using the sequence method. Across all conditions, BRS was lower in term born compared to preterm (13.0 ± 7.5 vs. 21.2 ± 8.8 ms⋅mmHg−1, main group effect: p < 0.01) participants. BRS was lower in HHx compared to NNx in term born (10.5 ± 4.9 vs. 16.0 ± 6.0 ms⋅mmHg−1, p = 0.05), but not in preterm (27.3 ± 15.7 vs. 17.6 ± 8.3 ms⋅mmHg−1, p = 0.43) participants, leading to a lower BRS in HHx in term born compared to preterm (p < 0.01). In conclusion, this study reports a blunted response of BRS during acute high‐altitude exposure without any influence of changes in inspired CO2 in healthy prematurely born adults. [ABSTRACT FROM AUTHOR]

Aging is accompanied by considerable deterioration of homeostatic systems, such as autonomic imbalance characterized by heightened sympathetic activity, lower parasympathetic tone, and depressed heart rate (HR) variability, which are aggravated by hypertension. Here, we hypothesized that these age-related deficits in aged hypertensive rats can be ameliorated by exercise training, with benefits to the cardiovascular system. Therefore, male 22-mo-old spontaneously hypertensive rats (SHRs) and agematched Wistar Kyoto (WKY) submitted to moderate-intensity exercise training (T) or kept sedentary (S) for 8 wk were evaluated for hemodynamic/autonomic parameters, baroreflex sensitivity, cardiac sympathetic/parasympathetic tone and analysis of dopamine β-hydroxylase (DBH+) and oxytocin (OT+) pathways of autonomic brain nuclei. Aged SHR-S versus WKY-S exhibited elevated mean arterial pressure (MAP: +51%) and HR (+20%), augmented pressure/HR variability, no cardiac vagal tone, and depressed reflex control of the heart (HR range, -28%; gain, -49%). SHR-T exhibited a lower resting HR, a partial reduction in the MAP (-14%), in the pressure/HR variabilities, and restored parasympathetic modulation, with improvement of baroreceptor reflex control when compared with SHR-S. Exercise training increased the ascending DBH+ projections conveying peripheral information to the paraventricular nucleus of hypothalamus (PVN), augmented the expression of OT+ neurons, and reduced the density of DBH+ neurons in the rostral ventrolateral medulla (RVLM) of SHR-T. Data indicate that exercise training induces beneficial neuroplasticity in brain autonomic circuitry, and it is highly effective to restore the parasympathetic tone, and attenuation of age-related autonomic imbalance and baroreflex dysfunction, thus conferring long-term benefits for cardiovascular control in aged hypertensive individuals. [ABSTRACT FROM AUTHOR]

The evaluation of propensity to postural syncope necessitates the concomitant characterization of the cardiovascular and cerebrovascular controls and a method capable of disentangling closed loop relationships and decomposing causal links in the frequency domain. We applied Geweke spectral causality (GSC) to assess cardiovascular control from heart period and systolic arterial pressure variability and cerebrovascular regulation from mean arterial pressure and mean cerebral blood velocity variability in 13 control subjects and 13 individuals prone to develop orthostatic syncope. Analysis was made at rest in supine position and during head-up tilt at 60°, well before observing presyncope signs. Two different linear model structures were compared, namely bivariate autoregressive and bivariate dynamic adjustment classes. We found that (i) GSC markers did not depend on the model structure; (ii) the concomitant assessment of cardiovascular and cerebrovascular controls was useful for a deeper comprehension of postural disturbances; (iii) orthostatic syncope appeared to be favored by the loss of a coordinated behavior between the baroreflex feedback and mechanical feedforward pathway in the frequency band typical of the baroreflex functioning during the postural challenge, and by a weak cerebral autoregulation as revealed by the increased strength of the pressure-to-flow link in the respiratory band. GSC applied to spontaneous cardiovascular and cerebrovascular oscillations is a promising tool for describing and monitoring disturbances associated with posture modification. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to test the hypothesis that patients with chronic kidney disease (CKD) would exhibit augmented resting beat-to-beat blood pressure variability (BPV) that is associated with poor clinical outcomes independent of mean blood pressure (BP). In addition, since the arterial baroreflex plays a critical role in beat-to-beat BP regulation, we further hypothesized that an impaired baroreflex control would be associated with an augmented resting beat-to-beat BPV. Methods: In 25 sedentary patients with CKD stages III–IV (62 ± 9 years) and 20 controls (57 ± 10 years), resting beat-to-beat BP (finger photoplethysmography) and heart rate (electrocardiography) were continuously measured for 10 min. We calculated the standard deviation (SD), average real variability (ARV) and other indices of BPV. The sequence technique was used to estimate spontaneous cardiac baroreflex sensitivity. Results: Compared with controls (CON), the CKD group had significantly increased resting BPV. The ARV (2.2 ± 0.6 versus 1.6 ± 0.5 mmHg, P < 0.001; 1.6 ± 0.7 versus 1.3 ± 0.3 mmHg, P = 0.039; 1.4 ± 0.5 versus 1.0 ± 0.2 mmHg, P < 0.001) of systolic, diastolic and mean BP, respectively, was increased in CKD versus controls. Other traditional measures of variability showed similar results. The cardiac baroreflex sensitivity was lower in CKD compared with controls (CKD: 8.4 ± 4.5 ms/mmHg versus CON: 14.0 ± 8.2 ms/mmHg, P = 0.008). In addition, cardiac baroreflex sensitivity was negatively associated with BPV [systolic blood pressure (SBP) ARV; r = −0.44, P = 0.003]. Conclusion: In summary, our data demonstrate that patients with CKD have augmented beat-to-beat BPV and lower cardiac baroreflex sensitivity. BPV and cardiac baroreflex sensitivity were negatively correlated in this cohort. These findings may further our understanding about cardiovascular dysregulation observed in patients with CKD. [ABSTRACT FROM AUTHOR]

Uncontrolled hypertension drives the global burden of increased cardiovascular disease (CVD) morbidity and mortality. Although high blood pressure (BP) is treatable and preventable, only half of the patients with hypertension undergoing treatment have their BP controlled. The failure of polypharmacy to attain adequate BP control may be due to a lack of physiological response, however, medication non-adherence and clinician inertia to increase treatment intensity are critical factors associated with poor hypertension management. The long-time medication titration, lifelong drug therapy, and often multi-drug treatment strategy are frustrating when the BP goal is not achieved, leading to increased CVD risk and a substantial burden on the healthcare system. Growing evidence indicates that neurohumoral activation is critical in initiating and maintaining elevated BP and its adverse consequences. Over the past decades, device-based therapies targeting the mechanisms underlying hypertension pathophysiology have been extensively studied. Among these, robust clinical experience for hypertension management exists for renal denervation (RDN) and baroreflex activation therapy (BAT), carotid body denervation (CBD), central arteriovenous anastomosis, and to a lesser extent, deep brain stimulation. Future studies are warranted to define the role of device-based approaches as an alternative or adjunctive treatment option to treat hypertension. Systemic hypertension is a growing contributor to global disease burden and premature cause of death worldwide. The percentage of patients achieving target BP levels remains largely inadequate. Hypertension is characterised by activation of the sympathetic nervous system, with the magnitude depending on age and the disease severity. Device-based interventions have been extensively studied to directly target the relevant sympathetic neural pathophysiological mechanisms involved in BP control. Modulation of the chronic sympathetic outflow with CBD or BAT shows promise for the treatment of poorly controlled hypertension in addition to antihypertensive medicines. The BP response to device-based therapies appears variable and cannot be predicted before the procedure. Until more robust evidence related to patient selection, procedural and technical aspects is available, chemoreflex and baroreflex neuromodulation therapy should be restricted to randomised sham-controlled trials performed in experienced centres. [ABSTRACT FROM AUTHOR]

Patients with heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF) exhibit severe exercise intolerance that may be due, in part, to inappropriate cardiovascular and hemodynamic adjustments to exercise. Several neural mechanisms and locally released vasoactive substances work in concert through complex interactions to ensure proper adjustments to meet the metabolic demands of the contracting skeletal muscle. Specifically, accumulating evidence suggests that disease-related alterations in neural mechanisms (e.g., central command, exercise pressor reflex, arterial baroreflex, and cardiopulmonary baroreflex) contribute to heightened sympathetic activation and impaired ability to attenuate sympathetic vasoconstrictor responsiveness that may contribute to reduced skeletal muscle blood flow and severe exercise intolerance in patients with HFrEF. In contrast, little is known regarding these important aspects of physiology in patients with HFpEF, though emerging data reveal heightened sympathetic activation and attenuated skeletal muscle blood flow during exercise in this patient population that may be attributable to dysregulated neural control of the circulation. The overall goal of this review is to provide a brief overview of the current understanding of disease-related alterations in the integrative neural cardiovascular responses to exercise in both HFrEF and HFpEF phenotypes, with a focus on sympathetic nervous system regulation during exercise. [ABSTRACT FROM AUTHOR]

Abstract An age‐associated increase in arterial blood pressure is evident for apparently healthy humans. This is frequently attributed to stiffening of the central arteries and a concurrent increase in sympathetic outflow, potentially mediated by a reduced ability of the baroreceptive vessels to distend. This is supported, in part, by a reduced mechanical component of the vascular sympathetic baroreflex (i.e., a reduction in distension for a given pressure). Previous characterization of the mechanical component has assessed only carotid artery distension; however, evidence suggests that both the aortic and carotid baroreflexes are integral to blood pressure regulation. In addition, given that baroreceptors are located in the vessel wall, the change in wall tension, comprising diameter, pressure and vessel wall thickness, and the mechanics of this change might provide a better index of the baroreceptor stimulus than the previous method used to characterize the mechanical component that relies on diameter alone. This brief review summarizes the data using this new method of assessing barosensory vessel mechanics and their influence on the vascular sympathetic baroreflex across the lifespan.

Aims: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) affects vital organs and causes vascular injury. There are concerns that this injury may have long-term consequences on the cardiovascular system after recovery from COVID-19. We investigated the incidence and predictors of new-onset hypertension at 1-year follow-up post-COVID-19 disease. Methods: In this prospective observational study, 393 patients hospitalised and diagnosed with COVID-19 disease at a tertiary cardiac care hospital during 27th March 2021 to 27th May 2021. Eligible 248 patients whose baseline characteristics, laboratory findings, treatment and outcome data were received systematically. Patients were followed up at 1 year of COVID-19 disease recovery. Results: We found that 32.3% of the population had new onset of hypertension at 1 year follow-up post-COVID-19 disease recovery. More hypertensive patients had severe computed tomography (CT) score severity (28.7 vs 14.9%; P 0.02). More number of patients in the hypertensive group were treated with steroids (73.8% vs 39%; p

This document summarizes a research letter that explores the effects of a drug called MK-2075 on heart rate and blood pressure in monkeys and humans. The study found that the drug caused a decrease in heart rate variability and baroreceptor sensitivity in monkeys, indicating an impact on sympathetic and parasympathetic tone. In human participants, the drug led to syncope in some cases. The study suggests that the drug may have negative effects on cardiovascular autonomic regulation, but more research is needed to fully understand its potential risks and benefits. [Extracted from the article]

Self-organized criticality is a universal theory for dynamical systems that has recently been applied to the cardiovascular system. Precise methodological approaches are essential for understanding the dynamics of cardiovascular self-organized criticality. This study examines how the duration and quality of data recording affect the analysis of cardiovascular self-organized criticality, with a focus on the beat-by-beat heart rate variability time series obtained from seven healthy subjects in a standing position. Drawing a Zipf diagram, we evaluated the distribution of cardiovascular events of bradycardia and tachycardia. We identified tipping points for the distribution of both bradycardia and tachycardia events. By varying the recording durations (1, 2, 5, 10, 20, 30, and 40 min) and sampling frequencies (500, 250, and 100 Hz), we investigated their influence on the observed distributions. While shorter recordings can effectively capture cardiovascular events, they may underestimate the variables describing their distribution. Additionally, the tipping point of the Zipf distribution differs between bradycardia and tachycardia events. Comparisons of the distribution of bradycardia and tachycardia events should be conducted using long data recordings. Utilizing devices with lower sampling frequencies may compromise data fidelity. These insights contribute to refining experimental protocols and advancing our understanding of the complex dynamics underlying cardiovascular regulation.