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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 -
Respiratory Physiology & Neurobiology Aug 2021The integrative physiological effects of O treatment on patients with pulmonary hypertension (PH) during exercise, have not been fully investigated. We simultaneously... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized placebo-control trial of the acute effects of oxygen supplementation on exercise hemodynamics, autonomic modulation, and brain oxygenation in patients with pulmonary hypertension.
BACKGROUND
The integrative physiological effects of O treatment on patients with pulmonary hypertension (PH) during exercise, have not been fully investigated. We simultaneously evaluated, for the first time, the effect of oxygen supplementation on hemodynamic responses, autonomic modulation, tissue oxygenation, and exercise performance in patients with pulmonary arterial hypertension (PAH)/Chronic Thromboembolic PH(CTEPH).
MATERIAL-METHODS
In this randomized, cross-over, placebo-controlled trial, stable outpatients with PAH/CTEPH underwent maximal cardiopulmonary exercise testing, followed by two submaximal trials, during which they received supplementary oxygen (O) or medical-air. Continuous, non-invasive hemodynamics were monitored via photophlythesmography. Cerebral and quadriceps muscle oxygenation were recorded via near-infrared spectroscopy. Autonomic function was assessed by heart rate variability; root mean square of successive differences (RMSSD) and standard-deviation-Poincare-plot (SD1) were used as indices of parasympathetic output. Baroreceptor sensitivity (BRS) was assessed throughout the protocols.
RESULTS
Nine patients (51.4 ± 9.4 years) were included. With O-supplementation patients exercised for longer (p = 0.01), maintained higher cerebral oxygenated hemoglobin (OHb;p = 0.02) levels, exhibited an amelioration in cortical deoxygenation (HHb;p = 0.02), and had higher average cardiac output (CO) during exercise (p < 0.05), compared to medical air; with no differences in muscle oxygenation. With O-supplementation patients exhibited higher BRS and sample-entropy throughout the protocol (p < 0.05) vs. medical air, and improved the blunted RMSSD, SD1 responses during exercise (p = 0.024).
CONCLUSION
We show that O administration improves BRS and autonomic function during submaximal exercise in PAH/CTEPH, without significantly affecting muscle oxygenation. The improved autonomic function, along with enhancements in cardiovascular function and cerebral oxygenation, probably contributes to increased exercise tolerance with O-supplementation in PH patients.
Topics: Adult; Autonomic Nervous System; Cross-Over Studies; Exercise; Exercise Test; Hemodynamics; Humans; Hypertension, Pulmonary; Middle Aged; Oxygen; Oxygen Inhalation Therapy; Pressoreceptors; Treatment Outcome
PubMed: 33957299
DOI: 10.1016/j.resp.2021.103677 -
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 -
Nutrition, Metabolism, and... May 2021Our previous study found carotid baroreceptor stimulation (CBS) reduces body weight and white adipose tissue (WAT) weight, restores abnormal secretion of adipocytokines...
BACKGROUND AND AIM
Our previous study found carotid baroreceptor stimulation (CBS) reduces body weight and white adipose tissue (WAT) weight, restores abnormal secretion of adipocytokines and inflammation factors, decreases systolic blood pressure (SBP) by inhibiting activation of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in obese rats. In this study, we explore effects of CBS on aortic remodeling in obese rats.
METHODS AND RESULTS
Rats were fed high-fat diet (HFD) for 16 weeks to induce obesity and underwent either CBS device implantation and stimulation or sham operation at 8 weeks. BP and body weight were measured weekly. RAS activity of WAT, histological, biochemical and functional profiles of aortas were detected after 16 weeks. CBS effectively decreased BP in obese rats, downregulated mRNA expression of angiotensinogen (AGT) and renin in WAT, concentrations of AGT, renin, angiotensin II (Ang II), protein levels of Ang II receptor 1 (AT1R) and Ang II receptor 2 (AT2R) in WAT were declined. CBS inhibited reactive oxygen species (ROS) generation, inflammatory response and endoplasmic reticulum (ER) stress in aortas of obese rats, restrained vascular wall thickening and vascular smooth muscle cells (VSMCs) phenotypic switching, increased nitric oxide (NO) synthesis, promoted endothelium-dependent vasodilatation by decreasing protein expression of AT1R and leptin receptor (LepR), increasing protein expression of adiponectin receptor 1 (AdipoR1) in aortic VSMCs.
CONCLUSION
CBS reduced BP and reversed aortic remodeling in obese rats, the underlying mechanism might be related to the suppressed SNS activity, restored adipocytokine secretion and restrained RAS activity of WAT.
Topics: Adipokines; Adipose Tissue, White; Animals; Aorta, Thoracic; Arterial Pressure; Disease Models, Animal; Electric Stimulation Therapy; Endothelial Cells; Implantable Neurostimulators; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Obesity; Pressoreceptors; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptors, Adiponectin; Receptors, Leptin; Renin-Angiotensin System; Vascular Remodeling; Vasodilation; Rats
PubMed: 33812737
DOI: 10.1016/j.numecd.2021.01.021 -
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 -
The American Journal of Cardiology Jun 2021The ECG findings during sudden collapse (syncope or sudden death) in severe aortic stenosis (AS) are not well defined. We conducted a comprehensive review of the... (Review)
Review
The ECG findings during sudden collapse (syncope or sudden death) in severe aortic stenosis (AS) are not well defined. We conducted a comprehensive review of the literature for ECG data during sudden collapse in patients with AS and provided a case report of our own. There were 37 published cases of syncope or sudden death in patients with severe AS which were documented by ECG. Brady- or ventricular arrhythmias were documented in 34 cases (92%). Bradyarrhythmia (n = 24; 71%) was more common at the time of collapse than ventricular tachyarrhythmia (n = 10; 29%). There was slowing of the sinus rate before bradyarrhythmia in the vast majority of patients with bradyarrhythmia but not in those presenting with ventricular tachyarrhythmia (75% vs 0%; p <0.001). ECG evidence of ischemia (ST-segment depression or elevation) was present in most patients with bradyarrhythmia but not in those with ventricular tachyarrhythmia (75% vs 0%; p = 0.011). In conclusion, our findings suggest that left ventricular baroreceptor activation plays a dominant role in the pathophysiology of sudden collapse in patients with severe AS and suggest that ischemia may play a role as well.
Topics: Aged; Aortic Valve Stenosis; Bicuspid Aortic Valve Disease; Bradycardia; Death, Sudden, Cardiac; Electrocardiography; Heart Ventricles; Humans; Male; Myocardial Ischemia; Pressoreceptors; Severity of Illness Index; Syncope; Tachycardia, Ventricular
PubMed: 33667448
DOI: 10.1016/j.amjcard.2021.02.023 -
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