-
Frontiers in Immunology 2021Baroreflex and chemoreflex act through the autonomic nervous system, which is involved with the neural regulation of inflammation. The present study reports the effects...
Baroreflex and chemoreflex act through the autonomic nervous system, which is involved with the neural regulation of inflammation. The present study reports the effects of reflex physiological sympathetic activation in endotoxemic rats using bilateral carotid occlusion (BCO), a physiological approach involving the baroreflex and chemoreflex mechanisms and the influence of the baroreceptors and peripheral chemoreceptors in the cardiovascular and systemic inflammatory responses. After lipopolysaccharide (LPS) administration, the arterial pressure was recorded during 360 min in unanesthetized rats, and serial blood samples were collected to analyze the plasma cytokine levels. BCO elicited the reflex activation of the sympathetic nervous system, providing the following outcomes: (I) increased the power of the low-frequency band in the spectrum of the systolic arterial pressure during the BCO period; (II) reduced the levels of pro-inflammatory cytokines in plasma, including the tumor necrosis factor (TNF) and the interleukin (IL)-1; (III) increased the plasma levels of anti-inflammatory cytokine IL-10, 90 min after LPS administration. Moreover, selective baroreceptor or chemoreceptor denervation deactivated mechanosensitive and chemical sensors, respectively, and decreased the release of the LPS-induced cytokine but did not alter the BCO modulatory effects. These results show, for the first time, that physiological reflex activation of the sympathetic circuit decreases the inflammatory response in endotoxemic rats and suggest a novel function for the baroreceptors as immunosensors during the systemic inflammation.
Topics: Animals; Autonomic Nervous System; Baroreflex; Blood Pressure; Chemoreceptor Cells; Endotoxemia; Inflammation; Interleukin-10; Interleukin-1beta; Lipopolysaccharides; Pressoreceptors; Rats; Rats, Wistar; Sympathetic Nervous System; Tumor Necrosis Factor-alpha
PubMed: 33995355
DOI: 10.3389/fimmu.2021.637845 -
Circulation Research Jul 2021[Figure: see text].
[Figure: see text].
Topics: Animals; Aortic Coarctation; Arterial Pressure; Cell Line; Cell Nucleus; Chromatin Assembly and Disassembly; Disease Models, Animal; Endocrine Cells; Female; Homeostasis; Integrin beta1; Kidney; Lamin Type A; Male; Mechanotransduction, Cellular; Mice, Knockout; Pressoreceptors; Renin; Stress, Mechanical; Mice
PubMed: 33993729
DOI: 10.1161/CIRCRESAHA.120.318711 -
Life Sciences Aug 2021Diabetes promotes renal sympathetic hyperactivity, autonomic imbalance, and cardiovascular and renal dysfunction. Bilateral renal denervation (BRD) has emerged as a...
UNLABELLED
Diabetes promotes renal sympathetic hyperactivity, autonomic imbalance, and cardiovascular and renal dysfunction. Bilateral renal denervation (BRD) has emerged as a treatment for diabetes; however, the mechanisms that underlie the beneficial effects of BRD are unknown.
AIMS
The present study evaluated the effects of BRD on autonomic, cardiovascular, metabolic, and renal function in streptozotocin-diabetic rats.
MAIN METHODS
Wistar rats were separated into three experimental groups: control (CTR), diabetic (DM), and diabetic that underwent BRD (DM BRD). BRD was performed two weeks after STZ-diabetes induction, the experiments were performed four weeks after DM induction. This study evaluated sympathetic vasomotor nerve activity in different territories (renal, lumbar and splanchnic), arterial baroreceptor reflex, metabolic and renal function.
KEY FINDINGS
BRD significantly reduced glycemia, glycosuria, albuminuria, and SGLT2 gene expression in the kidney in DM rats. Renal sympathetic nerve activity (rSNA) was significantly increased and splanchnic sympathetic nerve activity (sSNA) was significantly decreased in DM rats, without changes in lumbar sympathetic nerve activity (lSNA). BRD was able to normalize sSNA and significantly increase lSNA in DM rats compared to control rats. Additionally, cardiac baroreceptor sensitivity was impaired in DM rats, and BRD significantly improved baroreflex sensitivity.
SIGNIFICANCE
Our data suggest that renal nerves play an important role in autonomic, cardiovascular, and renal dysfunction in STZ-DM rats. Thus, sympathetic renal hyperactivity should be considered a possible therapeutic target in diabetic patients.
Topics: Animals; Baroreflex; Blood Pressure; Cardiovascular System; Catheterization; Denervation; Diabetes Mellitus, Experimental; Heart; Heart Rate; Hematocrit; Kidney; Male; Pressoreceptors; Rats; Rats, Wistar; Sodium-Glucose Transporter 2; Streptozocin; Sympathetic Nervous System
PubMed: 33933461
DOI: 10.1016/j.lfs.2021.119534 -
Circulation. Arrhythmia and... Apr 2021Symptomatic heart failure (HF) patients despite optimal medical therapy and advances such as invasive hemodynamic monitoring remain challenging to manage. While cardiac... (Review)
Review
Symptomatic heart failure (HF) patients despite optimal medical therapy and advances such as invasive hemodynamic monitoring remain challenging to manage. While cardiac resynchronization therapy remains a highly effective therapy for a subset of HF patients with wide QRS, a majority of symptomatic HF patients are poor candidates for such. Recently, cardiac contractility modulation, neuromodulation based on carotid baroreceptor stimulation, and phrenic nerve stimulation have been approved by the US Food and Drug Administration and are emerging as therapeutic options for symptomatic HF patients. This state-of-the-art review examines the role of these evolving electrical therapies in advanced HF.
Topics: Animals; Autonomic Nervous System; Cardiac Pacing, Artificial; Electric Stimulation Therapy; Heart; Heart Failure; Humans; Myocardial Contraction; Pacemaker, Artificial; Prevalence; Recovery of Function; Spinal Cord Stimulation; Stroke Volume; Treatment Outcome; Vagus Nerve Stimulation; Ventricular Function, Left
PubMed: 33858178
DOI: 10.1161/CIRCEP.120.009668 -
BMC Cardiovascular Disorders Mar 2021The study evaluated the cost of baroreflex activation therapy plus guideline directed therapy (BAT + GDT) compared to GDT alone for HF patients with reduced ejection... (Comparative Study)
Comparative Study
BACKGROUND
The study evaluated the cost of baroreflex activation therapy plus guideline directed therapy (BAT + GDT) compared to GDT alone for HF patients with reduced ejection fraction and New York Heart Association Class III or II (with a recent history of III). Baroreflex activation therapy (BAT) is delivered by an implantable device that stimulates the baroreceptors through an electrode attached to the outside of the carotid artery, which rebalances the autonomic nervous system to regain cardiovascular (CV) homeostasis. The BeAT-HF trial evaluated the safety and effectiveness of BAT.
METHODS
A cost impact model was developed from a U.S. health care payer or integrated delivery network perspective over a 3-year period for BAT + GDT versus GDT alone. Expected costs were calculated by utilizing 6-month data from the BeAT-HF trial and existing literature. HF hospitalization rates were extrapolated based on improvement in NT-proBNP.
RESULTS
At baseline the expected cost of BAT + GDT were $29,526 per patient more than GDT alone due to BAT device and implantation costs. After 3 years, the predicted cost per patient was $9521 less expensive for BAT + GDT versus GDT alone due to lower rates of significant HF hospitalizations, CV non-HF hospitalizations, and resource intensive late-stage procedures (LVADs and heart transplants) among the BAT + GDT group.
CONCLUSIONS
BAT + GDT treatment becomes less costly than GDT alone beginning between years 1 and 2 and becomes less costly cumulatively between years 2 and 3, potentially providing significant savings over time. As additional BeAT-HF trial data become available, the model can be updated to show longer term effects.
Topics: Baroreflex; Chronic Disease; Cost Savings; Cost-Benefit Analysis; Electric Stimulation Therapy; Health Care Costs; Heart Failure; Humans; Models, Economic; Outcome and Process Assessment, Health Care; Pressoreceptors; Time Factors; Treatment Outcome; United States
PubMed: 33771104
DOI: 10.1186/s12872-021-01958-y -
Experimental Physiology May 2021Cardio-ventilatory coupling refers to the onset of inspiration occurring at a preferential latency following the last heartbeat (HB) in expiration. According to the...
NEW FINDINGS
Cardio-ventilatory coupling refers to the onset of inspiration occurring at a preferential latency following the last heartbeat (HB) in expiration. According to the cardiac-trigger hypothesis, the pulse pressure initiates an inspiration via baroreceptor activation. However, the central neural substrate mediating this coupling remains undefined. Using a combination of animal data, human data and mathematical modelling, this study tests the hypothesis that the HB, by way of pulsatile baroreflex activation, controls the initiation of inspiration that occurs through a rapid neural activation loop from the carotid baroreceptors to Bötzinger complex expiratory neurons.
ABSTRACT
Cardio-ventilatory coupling refers to a heartbeat (HB) occurring at a preferred latency prior to the next breath. We hypothesized that the pressure pulse generated by a HB activates baroreceptors that modulate brainstem expiratory neuronal activity and delay the initiation of inspiration. In supine male subjects, we recorded ventilation, electrocardiogram and blood pressure during 20-min epochs of baseline, slow-deep breathing and recovery. In in situ rodent preparations, we recorded brainstem activity in response to pulses of perfusion pressure. We applied a well-established respiratory network model to interpret these data. In humans, the latency between a HB and onset of inspiration was consistent across different breathing patterns. In in situ preparations, a transient pressure pulse during expiration activated a subpopulation of expiratory neurons normally active during post-inspiration, thus delaying the next inspiration. In the model, baroreceptor input to post-inspiratory neurons accounted for the effect. These studies are consistent with baroreflex activation modulating respiration through a pauci-synaptic circuit from baroreceptors to onset of inspiration.
Topics: Animals; Baroreflex; Blood Pressure; Heart Rate; Humans; Male; Pressoreceptors; Respiration
PubMed: 33749038
DOI: 10.1113/EP089365 -
Clinical Autonomic Research : Official... Aug 2021The present paper will review the impact of different therapeutic interventions on the autonomic dysfunction characterizing chronic renal failure. (Review)
Review
PURPOSE
The present paper will review the impact of different therapeutic interventions on the autonomic dysfunction characterizing chronic renal failure.
METHODS
We reviewed the results of the studies carried out in the last few years examining the effects of standard pharmacologic treatment, hemodialysis, kidney transplantation, renal nerve ablation and carotid baroreceptor stimulation on parasympathetic and sympathetic control of the cardiovascular system in patients with renal failure.
RESULTS
Drugs acting on the renin-angiotensin system as well as central sympatholytic agents have been documented to improve autonomic cardiovascular control. This has also been shown for hemodialysis, although with more heterogeneous results related to the type of dialytic procedure adopted. Kidney transplantation, in contrast, particularly when performed together with the surgical removal of the native diseased kidneys, has been shown to cause profound sympathoinhibitory effects. Finally, a small amount of promising data are available on the potential favorable autonomic effects (particularly the sympathetic ones) of renal nerve ablation and carotid baroreceptor stimulation in chronic kidney disease.
CONCLUSIONS
Further studies are needed to clarify several aspects of the autonomic responses to therapeutic interventions in chronic renal disease. These include (1) the potential to normalize sympathetic activity in uremic patients by the various therapeutic approaches and (2) the definition of the degree of sympathetic deactivation to be achieved during treatment.
Topics: Autonomic Nervous System; Cardiovascular System; Humans; Kidney; Pressoreceptors; Renal Insufficiency, Chronic; Sympathetic Nervous System
PubMed: 33606138
DOI: 10.1007/s10286-021-00786-6 -
Comprehensive Physiology Feb 2021Baroreceptors are mechanosensitive elements of the peripheral nervous system that maintain cardiovascular homeostasis by coordinating the responses to external and...
Baroreceptors are mechanosensitive elements of the peripheral nervous system that maintain cardiovascular homeostasis by coordinating the responses to external and internal environmental stressors. While it is well known that carotid and cardiopulmonary baroreceptors modulate sympathetic vasomotor and parasympathetic cardiac neural autonomic drive, to avoid excessive fluctuations in vascular tone and maintain intravascular volume, there is increasing recognition that baroreceptors also modulate a wide range of non-cardiovascular physiological responses via projections from the nucleus of the solitary tract to regions of the central nervous system, including the spinal cord. These projections regulate pain perception, sleep, consciousness, and cognition. In this article, we summarize the physiology of baroreceptor pathways and responses to baroreceptor activation with an emphasis on the mechanisms influencing cardiovascular function, pain perception, consciousness, and cognition. Understanding baroreceptor-mediated effects on cardiac and extra-cardiac autonomic activities will further our understanding of the pathophysiology of multiple common clinical conditions, such as chronic pain, disorders of consciousness (e.g., abnormalities in sleep-wake), and cognitive impairment, which may result in the identification and implementation of novel treatment modalities. © 2021 American Physiological Society. Compr Physiol 11:1373-1423, 2021.
Topics: Consciousness; Heart; Humans; Pain; Parasympathetic Nervous System; Pressoreceptors; Sympathetic Nervous System
PubMed: 33577130
DOI: 10.1002/cphy.c190038 -
Scientific Reports Jan 2021Head-down bed rest (HDBR) has previously been shown to alter cerebrovascular and autonomic control. Previous work found that sustained HDBR (≥ 20 days) attenuates... (Randomized Controlled Trial)
Randomized Controlled Trial
Head-down bed rest (HDBR) has previously been shown to alter cerebrovascular and autonomic control. Previous work found that sustained HDBR (≥ 20 days) attenuates the hypercapnic ventilatory response (HCVR); however, little is known about shorter-term effects of HDBR nor the influence of HDBR on the hypoxic ventilatory response (HVR). We investigated the effect of 4-h HDBR on HCVR and HVR and hypothesized attenuated ventilatory responses due to greater carotid and brain blood flow. Cardiorespiratory responses of young men (n = 11) and women (n = 3) to 5% CO or 10% O before and after 4-h HDBR were examined. HDBR resulted in lower HR, lower cardiac output index, lower common carotid artery flow, higher SpO, and higher pulse wave velocity. After HDBR, tidal volume and ventilation responses to 5% CO were enhanced (all P < 0.05), yet no other changes in cardiorespiratory variables were evident. There was no influence of HDBR on the cardiorespiratory responses to hypoxia (all P > 0.05). Short-duration HDBR does not alter the HVR, yet enhances the HCVR, which we hypothesize is a consequence of cephalic CO accumulation from cerebral congestion.
Topics: Bed Rest; Blood Pressure; Female; Head-Down Tilt; Heart Rate; Humans; Hypercapnia; Hypoxia; Male; Middle Cerebral Artery; Pressoreceptors; Respiration; Stroke Volume; Tidal Volume; Vascular Resistance; Young Adult
PubMed: 33495489
DOI: 10.1038/s41598-021-81837-w -
Circulation. Heart Failure Jan 2021Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse...
Impairments in Blood Pressure Regulation and Cardiac Baroreceptor Sensitivity Among Patients With Heart Failure Supported With Continuous-Flow Left Ventricular Assist Devices.
BACKGROUND
Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation.
METHODS
Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30 and 60. Heart rate and BP were monitored during cardiopulmonary exercise testing.
RESULTS
Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved-but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing.
CONCLUSIONS
Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078972.
Topics: Aged; Baroreflex; Blood Pressure; Exercise Test; Female; Heart Failure; Heart Rate; Heart-Assist Devices; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Pressoreceptors; Valsalva Maneuver
PubMed: 33464953
DOI: 10.1161/CIRCHEARTFAILURE.120.007448