Article

Effects of Chronic Baroreceptor Stimulation on the Autonomic Cardiovascular Regulation in Patients With Drug-Resistant Arterial Hypertension

August 2009
Hypertension 54(3):530-6

August 2009
54(3):530-6

DOI:10.1161/HYPERTENSIONAHA.109.134023

Source
PubMed

Authors:

Kerstin Wustmann

Deutsches Herzzentrum München

Ingrid Scheffers

Hogeschool Fontys

Markus Mohaupt

Inselspital, Universitätsspital Bern

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In patients with drug-resistant hypertension, chronic electric stimulation of the carotid baroreflex is an investigational therapy for blood pressure reduction. We hypothesized that changes in cardiac autonomic regulation can be demonstrated in response to chronic baroreceptor stimulation, and we analyzed the correlation with blood pressure changes. Twenty-one patients with drug-resistant hypertension were prospectively included in a substudy of the Device Based Therapy in Hypertension Trial. Heart rate variability and heart rate turbulence were analyzed using 24-hour ECG. Recordings were obtained 1 month after device implantation with the stimulator off and after 3 months of chronic electric stimulation (stimulator on). Chronic baroreceptor stimulation decreased office blood pressure from 185+/-31/109+/-24 mm Hg to 154+/-23/95+/-16 mm Hg (P<0.0001/P=0.002). Mean heart rate decreased from 81+/-11 to 76+/-10 beats per minute(-1) (P=0.001). Heart rate variability frequency-domain parameters assessed using fast Fourier transformation (FFT; ratio of low frequency:high frequency: 2.78 versus 2.24 for off versus on; P<0.001) were significantly changed during stimulation of the carotid baroreceptor, and heart rate turbulence onset was significantly decreased (turbulence onset: -0.002 versus -0.015 for off versus on; P=0.004). In conclusion, chronic baroreceptor stimulation causes sustained changes in heart rate variability and heart rate turbulence that are consistent with inhibition of sympathetic activity and increase of parasympathetic activity in patients with drug-resistant systemic hypertension; these changes correlate with blood pressure reduction. Whether the autonomic modulation has favorable cardiovascular effects beyond blood pressure control should be investigated in further studies.

Baroreflex activation therapy in patients with heart failure with reduced ejection fraction: a single-centre experience

Article

Full-text available

Sep 2023

Aims: Heart failure with reduced ejection fraction (HFrEF) is associated with excessive sympathetic and impaired parasympathetic activity. The Barostim Neo™ device is used for electronical baroreflex activation therapy (BAT) to counteract autonomic nervous system dysbalance. Randomized trials have shown that BAT improves walking distance and reduces N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels at least in patients with only moderate elevation at baseline. Its impact on the risk of heart failure hospitalization (HFH) and death is not yet established, and experience in clinical routine is limited. Methods and results: We report on patient characteristics and clinical outcome in a retrospective, non-randomized single-centre registry of BAT in HFrEF. Patients in the New York Heart Association (NYHA) Classes III and IV with a left ventricular ejection fraction (LVEF) <35% despite guideline-directed medical therapy were eligible. Symptom burden, echocardiography, and laboratory testing were assessed at baseline and after 12 months. Clinical events of HFH and death were recorded at routine clinical follow-up. Data are shown as number (%) or median (inter-quartile range). Between 2014 and 2020, 30 patients were treated with BAT. Median age was 67 (63-77) years, and 27 patients (90%) were male. Most patients (83%) had previous HFH. Device implantation was successful in all patients. At 12 months, six patients had died and three were alive but did not attend follow-up. NYHA class was III/IV in 26 (87%)/4 (13%) patients at baseline, improved in 19 patients, and remained unchanged in 5 patients (P < 0.001). LVEF improved from 25.5 (20.0-30.5) % at baseline to 30.0 (25.0-36.0) % at 12 months (P = 0.014). Left ventricular end-diastolic diameter remained unchanged. A numerical decrease in NT-proBNP [3165 (880-8085) vs. 1001 (599-3820) pg/mL] was not significant (P = 0.526). Median follow-up for clinical events was 16 (10-33) months. Mortality at 1 (n = 6, 20%) and 3 years (n = 10, 33%) was as expected by the Meta-Analysis Global Group in Chronic Heart Failure risk score. Despite BAT, event rate was high in patients with NYHA Class IV, NT-proBNP levels >1600 pg/mL, or estimated glomerular filtration rate (eGFR) <30 mL/min at baseline. NYHA class and eGFR were independent predictors of mortality. Conclusions: Patients with HFrEF who are selected for BAT are in a stage of worsening or even advanced heart failure. BAT appears to be safe and improves clinical symptoms and-to a modest degree-left ventricular function. The risk of death remains high in advanced disease stages. Patient selection seems to be crucial, and the impact of BAT in earlier disease stages needs to be established.

Effect of baroreflex activation therapy on dipping pattern in patients with resistant hypertension

Article

Full-text available

Dec 2022
J Clin Hypertens

A relevant number of patients with resistant hypertension do not achieve blood pressure (BP) dipping during nighttime. This inadequate nocturnal BP reduction is associated with elevated cardiovascular risks. The aim of this study was to evaluate whether a nighttime intensification of BAT might improve nocturnal BP dipping. In this prospective observational study, non-dippers treated with BAT for at least 6 months were included. BAT programming was modified in a two-step intensification of nighttime stimulation at baseline and week 6. Twenty-four hours ambulatory BP (ABP) was measured at inclusion and after 3 months. A number of 24 patients with non- or inverted dipping pattern, treated with BAT for a median of 44 months (IQR 25-52) were included. At baseline of the study, patients were 66 ± 9 years old, had a BMI of 33 ± 6 kg/m2 , showed an office BP of 135 ± 22/72 ± 10 mmHg, and took a median number of antihypertensives of 6 (IQR 4-9). Nighttime stimulation of BAT was adapted by an intensification of pulse width from 237 ± 161 to 267 ± 170 μs (p = .003) while frequency (p = .10) and amplitude (p = .95) remained unchanged. Uptitration of BAT programming resulted in an increase of systolic dipping from 2 ± 6 to 6 ± 8% (p = .03) accompanied with a significant improvement of dipping pattern (p = .02). Twenty four hours ABP, day- and nighttime ABP remained unchanged. Programming of an intensified nighttime BAT interval improved dipping profile in patients treated with BAT, while the overall 24 h ABP did not change. Whether the improved dipping response contributes to a reduction of cardiovascular risk beyond the BP-lowering effects of BAT, however, remains to be shown.

Exaggerated Exercise Blood Pressure as a Marker of Baroreflex Dysfunction in Normotensive Metabolic Syndrome Patients

Article

Full-text available

Jun 2021

Introduction Exaggerated blood pressure response to exercise (EEBP = SBP ≥ 190 mmHg for women and ≥210 mmHg for men) during cardiopulmonary exercise test (CPET) is a predictor of cardiovascular risk. Sympathetic hyperactivation and decreased baroreflex sensitivity (BRS) seem to be involved in the progression of metabolic syndrome (MetS) to cardiovascular disease. Objective To test the hypotheses: (1) MetS patients within normal clinical blood pressure (BP) may present EEBP response to maximal exercise and (2) increased muscle sympathetic nerve activity (MSNA) and reduced BRS are associated with this impairment. Methods We selected MetS (ATP III) patients with normal BP (MetS_NT, n = 27, 59.3% males, 46.1 ± 7.2 years) and a control group without MetS (C, n = 19, 48.4 ± 7.4 years). We evaluated BRS for increases (BRS+) and decreases (BRS−) in spontaneous BP and HR fluctuations, MSNA (microneurography), BP from ambulatory blood pressure monitoring (ABPM), and auscultatory BP during CPET. Results Normotensive MetS (MetS_NT) had higher body mass index and impairment in all MetS risk factors when compared to the C group. MetS_NT had higher peak systolic BP (SBP) (195 ± 17 vs. 177 ± 24 mmHg, P = 0.007) and diastolic BP (91 ± 11 vs. 79 ± 10 mmHg, P = 0.001) during CPET than C. Additionally, we found that MetS patients with normal BP had lower spontaneous BRS− (9.6 ± 3.3 vs. 12.2 ± 4.9 ms/mmHg, P = 0.044) and higher levels of MSNA (29 ± 6 vs. 18 ± 4 bursts/min, P < 0.001) compared to C. Interestingly, 10 out of 27 MetS_NT (37%) showed EEBP (MetS_NT+), whereas 2 out of 19 C (10.5%) presented (P = 0.044). The subgroup of MetS_NT with EEBP (MetS_NT+, n = 10) had similar MSNA (P = 0.437), but lower BRS+ (P = 0.039) and BRS− (P = 0.039) compared with the subgroup without EEBP (MetS_NT−, n = 17). Either office BP or BP from ABPM was similar between subgroups MetS_NT+ and MetS_NT−, regardless of EEBP response. In the MetS_NT+ subgroup, there was an association of peak SBP with BRS− (R = −0.70; P = 0.02), triglycerides with peak SBP during CPET (R = 0.66; P = 0.039), and of triglycerides with BRS− (R = 0.71; P = 0.022). Conclusion Normotensive MetS patients already presented higher peak systolic and diastolic BP during maximal exercise, in addition to sympathetic hyperactivation and decreased baroreflex sensitivity. The EEBP in MetS_NT with apparent well-controlled BP may indicate a potential depressed neural baroreflex function, predisposing these patients to increased cardiovascular risk.

The ability of baroreflex activation to improve blood pressure and resistance vessel function in spontaneously hypertensive rats is dependent on stimulation parameters

Article

Mar 2021

Baroreflex activation by electric stimulation of the carotid sinus (CS) effectively lowers blood pressure. However, the degree to which differences between stimulation protocols impinge on cardiovascular outcomes has not been defined. To address this, we examined the effects of short- and long-duration (SD and LD) CS stimulation on hemodynamic and vascular function in spontaneously hypertensive rats (SHRs). We fit animals with miniature electrical stimulators coupled to electrodes positioned around the left CS nerve that delivered intermittent 5/25 s ON/OFF (SD) or 20/20 s ON/OFF (LD) square pulses (1 ms, 3 V, 30 Hz) continuously applied for 48 h in conscious animals. A sham-operated control group was also studied. We measured mean arterial pressure (MAP), systolic blood pressure variability (SBPV), heart rate (HR), and heart rate variability (HRV) for 60 min before stimulation, 24 h into the protocol, and 60 min after stimulation had stopped. SD stimulation reversibly lowered MAP and HR during stimulation. LD stimulation evoked a decrease in MAP that was sustained even after stimulation was stopped. Neither SD nor LD had any effect on SBPV or HRV when recorded after stimulation, indicating no adaptation in autonomic activity. Both the contractile response to phenylephrine and the relaxation response to acetylcholine were increased in mesenteric resistance vessels isolated from LD-stimulated rats only. In conclusion, the ability of baroreflex activation to modulate hemodynamics and induce lasting vascular adaptation is critically dependent on the electrical parameters and duration of CS stimulation.

Maternal Separation Diminishes Alpha-Adrenergic Receptors Density and Function in Renal Vasculature from male Wistar Kyoto rats

Article

Mar 2017

Analysis of beat-to-beat blood pressure variability response to the cold pressor test in the offspring of hypertensive and normotensive parents

Article

Feb 2017

Abnormal autonomic nervous regulation has an important role in the development of hypertension. As to whether blood pressure (BP) or BP variability represents the proper characteristics for predisposition to hypertension in Chinese young adults remains controversial. We studied the properties of the indices extracted from beat-to-beat BP during a 13 min cold pressor test (CPT). In this study, 69 Chinese young adults including 34 offspring of hypertensive parents (OHPs; 25.6±2.5 years) and 35 offspring of normotensive parents (ONPs; 25.3±2.3 years) were analyzed. We assessed the differences between the two groups regarding mean beat-to-beat BP and variability indices. Beat-to-beat BP variability indices included time-domain indices and frequency-domain indices. Our results showed that the differences in beat-to-beat systolic BP and mean BP levels between the OHPs and the ONPs were statistically significant (P<0.05). Furthermore, more BP variability indices in the frequency domain were significantly different between the two groups. We concluded that BP variability was superior to BP as an index to evaluate the cardiovascular and sympathetic reactivity to the CPT. Moreover, compared with time-domain BP variability, we found more differences in frequency-domain BP variability between the two groups, thus indicating that frequency-domain BP variability may be a potential index of predisposition to hypertension.Hypertension Research advance online publication, 9 February 2017; doi:10.1038/hr.2017.4.

Neurovisceral interactions within the brain-heart axis as the basis of neurocardiology

Article

Full-text available

Nov 2022

The use of a systematic approach to the study of the etiology of a certain pathology makes it possible to improve the understanding of its pathogenesis, as well as to develop more effective diagnostic and therapeutic approaches, including improving the prediction of its risk. Within this review, we will consider such an area of interdisciplinary research as neurocardiology, which studies the brain-heart axis. Examples of cardiovascular diseases associated with organic and functional disorders of this axis will be considered, as well as the prospects for research in this area and their translational significance for clinical medicine.

Correction of carotid artery stenosis by stent placement ameliorated paroxysmal hypertension after radiation treatment of hypopharyngeal carcinoma: a case report

Article

Full-text available

Feb 2022
J Med Case Rep

Background Paroxysmal hypertension can be associated with failure of the carotid artery baroreceptors due to past exposure to radiation treatment. This report describes a patient whose repeated paroxysmal hypertensive episodes were ameliorated following placement of a carotid artery stent for the treatment of carotid artery stenosis. Case report A 79-year-old caucasian male was diagnosed with hypopharyngeal squamous cell carcinoma (T1, L0, M0) in 2006, and received 70 Gy intensity-modulated radiotherapy in 2006 and underwent a total laryngectomy in 2008. He experienced paroxysmal hypertensive episodes since 2010 that exacerbated in frequency in 2019. Eighty percent left internal carotid artery stenosis was demonstrated by ultrasound and arteriography. Angioplasty and stenting of the left carotid artery was performed. A Doppler ultrasound study performed 5 months after the stent placement did not reveal any hemodynamic stenosis in the left carotid artery. The patient experienced postprandial hypotension and had experienced only three episodes of paroxysmal hypertension in the following 24 months. He was able to abort paroxysmal hypertensive episodes by eating warm food. Discussion This is the first report of a patient whose paroxysmal hypertensive episodes that occurred following radiation of the neck subsided after placement of a stent in a stenotic carotid artery. The exact mechanism leading to this phenomena is unknown but may be due to several factors. The reversal of the carotid artery stent and improvement in blood flow to the carotid artery baroceptors may play a role in this phenomenon. Conclusion The ability to ameliorate paroxysmal hypertensive episodes in a patient with carotid artery stenosis by stent placement may be a promising therapeutic intervention for paroxysmal hypertension.

Targeting sympathetic glia for treating cardiovascular diseases

Method

Full-text available

Aug 2017

Gq G protein-coupled receptor (Gq-GPCR) signaling in glial fibrillary acidic protein-expressing (GFAP +) glia is essential for neuron-glia interaction in the Central Nervous System (CNS). However, the exploration of the roles of Gq-GPCR signaling in peripheral GFAP + glia has just begun. Our recent study showed that GFAP + glia in the sympathetic ganglia, namely satellite glial cells (SGCs), positively modulate sympathetic-regulated cardiac functions following their Gq-GPCR activation. In this research highlight, we discuss the significance of satellite glial modulation of sympathetic nerve activity (SNA) in both physiology and in diseases. We also present a new experimental strategy for manipulating satellite glial signaling in the sympathetic ganglia using adeno-associated virus (AAV). The success of targeted viral transduction in ganglionic SGCs suggest a strong therapeutic potential of targeting sympathetic glia for the treatment of cardiovascular diseases (CVDs).

Chronic Limb Remote Ischemic Conditioning may have an Antihypertensive Effect in Patients with Hypertension

Article

Full-text available

Dec 2021

Hypertension is the leading preventable risk factor for all-cause morbidity and mortality worldwide. Despite antihypertensive medications have been available for decades, a big challenge we are facing is to increase the blood pressure (BP) control rate among the population. Therefore, it is necessary to search for new antihypertensive means to reduce the burden of disease caused by hypertension. Limb remote ischemic conditioning (LRIC) can trigger endogenous protective effects through transient and repeated ischemia on the limb to protect specific organs and tissues including the brain, heart, and kidney. The mechanisms of LRIC involve the regulation of the autonomic nervous system, releasing humoral factors, improvement of vascular endothelial function, and modulation of immune/inflammatory responses. These underlying mechanisms of LRIC may restrain the pathogenesis of hypertension through multiple pathways theoretically, leading to a potential decline in BP. Several existing studies have explored the impact of LRIC on BP, however, controversial findings were reported. To explore the potential antihypertensive effect of LRIC and the underlying mechanisms, we systematically reviewed the relevant articles to provide an insight into the novel therapy of hypertension.

Device-Based Sympathetic Nerve Regulation for Cardiovascular Diseases

Article

Full-text available

Dec 2021

Sympathetic overactivation plays an important role in promoting a variety of pathophysiological processes in cardiovascular diseases (CVDs), including ventricular remodeling, vascular endothelial injury and atherosclerotic plaque progression. Device-based sympathetic nerve (SN) regulation offers a new therapeutic option for some CVDs. Renal denervation (RDN) is the most well-documented method of device-based SN regulation in clinical studies, and several large-scale randomized controlled trials have confirmed its value in patients with resistant hypertension, and some studies have also found RDN to be effective in the control of heart failure and arrhythmias. Pulmonary artery denervation (PADN) has been clinically shown to be effective in controlling pulmonary hypertension. Hepatic artery denervation (HADN) and splenic artery denervation (SADN) are relatively novel approaches that hold promise for a role in cardiovascular metabolic and inflammatory-immune related diseases, and their first-in-man studies are ongoing. In addition, baroreflex activation, spinal cord stimulation and other device-based therapies also show favorable outcomes. This review summarizes the pathophysiological rationale and the latest clinical evidence for device-based therapies for some CVDs.

Stress-sensitive arterial hypertension and tolerance to the salt loading in the ISIAH rats

Article

Full-text available

Dec 2020

The aim of the study is to investigate the ability of ISIAH rats with stress-sensitive arterial hypertension to cope with the salt loading. Hypertensive ISIAH and normotensive WAG rats were kept in metabolic cages for 7 days on three drinking regimes: group 1 – no salt loading (tap water), group 2 – saline solution (0.87% NaCl), and group 3 – 1,5% NaCl solution. After 7 days, no significant changes in the blood pressure in either WAG or ISIAH rats was observed. No differences between hypertensive and normotensive rats were found in the ability to excrete NaCl with urine. Glomerular filtration rates in ISIAH rats receiving both isotonic (saline) and hypertonic salt solutions were significantly higher than in the corresponding groups of WAG rats. In ISIAH, but not in WAG rats, receiving a hypertonic salt solution was accompanied by an increase in the concentrations of norepinephrine and epinephrine in urine. No significant changes in the function of renin-aldosterone system were observed. These and previously obtained results lead to the conclusion that not renal mechanisms but rather sympathetic nervous activity underlies the early development of arterial hypertension in stress-sensitive ISIAH rats, which are well tolerated to the salt loadings at this period of ascending pathology.

Device Therapy of Hypertension

Article

Full-text available

Apr 2021
CIRC RES

In the past decade, efforts to improve blood pressure control have looked beyond conventional approaches of lifestyle modification and drug therapy to embrace interventional therapies. Based upon animal and human studies clearly demonstrating a key role for the sympathetic nervous system in the etiology of hypertension, the newer technologies that have emerged are predominantly aimed at neuromodulation of peripheral nervous system targets. These include renal denervation, baroreflex activation therapy, endovascular baroreflex amplification therapy, carotid body ablation, and pacemaker-mediated programmable hypertension control. Of these, renal denervation is the most mature, and with a recent series of proof-of-concept trials demonstrating the safety and efficacy of radiofrequency and more recently ultrasound-based renal denervation, this technology is poised to become available as a viable treatment option for hypertension in the foreseeable future. With regard to baroreflex activation therapy, endovascular baroreflex amplification, carotid body ablation, and programmable hypertension control, these are developing technologies for which more human data are required. Importantly, central nervous system control of the circulation remains a poorly understood yet vital component of the hypertension pathway and mandates further investigation. Technology to improve blood pressure control through deep brain stimulation of key cardiovascular control territories is, therefore, of interest. Furthermore, alternative nonsympathomodulatory intervention targeting the hemodynamics of the circulation may also be worth exploring for patients in whom sympathetic drive is less relevant to hypertension perpetuation. Herein, we review the aforementioned technologies with an emphasis on the preclinical data that underpin their rationale and the human evidence that supports their use.

Protective Face Masks: Effect on the Oxygenation and Heart Rate Status of Oral Surgeons during Surgery

Article

Full-text available

Feb 2021
Int J Environ Res Publ Health

Background: Safety in medical work requires eye protection, such as glasses, and protective facial masks (PFM) during clinical practice to prevent viral respiratory infections. The use of facial masks and other full personal protective equipment increases air flow resistance, facial skin temperature and physical discomfort. The aim of the present study was to measure surgeons' oxygenation status and discomfort before and after their daily routine activities of oral interventions. Methods: 10 male voluntary dentists, specializing in oral surgery, and 10 male voluntary doctors in dentistry, participating in master's courses in oral surgery in the Department of Oral Surgery of the University of Chieti, with mean age 29 ± 6 (27-35), were enrolled. This study was undertaken to investigate the effects of wearing a PFM on oxygenation status while the oral surgeons were actively working. Disposable sterile one-way surgical paper masks (Surgical Face Mask, Euronda, Italy) and FFP2 (Surgical Face Mask, Euronda, Italy) were used and the mask position covering the nose did not vary during the procedures. The FFP2 was covered by a surgical mask during surgical treatment. A pulse oximeter was used to measure the blood oximetry saturation during the study. Results: In all 20 surgeons wearing FFP2 covered by surgical masks, a reduction in arterial O2 saturation from around 97.5% before surgery to 94% after surgery was recorded with increase of heart rates. A shortness of breath and light-headedness/headaches were also noted. Conclusions: In conclusion, wearing an FFP2 covered by a surgical mask induces a reduction in circulating O2 concentrations without clinical relevance, while an increase of heart frequency and a sensation of shortness of breath, light-headedness/headaches were recorded.

Barorezeptoraktivierungstherapie bei Herzinsuffizienz mit reduzierter systolischer Funktion

Article

Nov 2020

There is an urgent need for novel therapeutic concepts as adjuncts to guideline-directed medicinal and nonpharmaceutical treatment of heart failure. The sympathetic nervous system is central to the neurohumoral activation during heart failure due to impaired feedback inhibition, leading to direct and indirect cardiotoxicity and adverse myocardial remodeling. Baroreceptor activation therapy (BAT) is an innovative treatment of heart failure based on electrical stimulation of carotid artery baroreceptors. On stimulation of these receptors, sympathetic outflow is reduced through negative feedback loops. In this review article we briefly review the underlying basic physiology of the baroreflex and present the currently available preclinical and clinical data on BAT in heart failure.

Microchannel Electrode Stimulation of Deep Peroneal Nerve Fascicles Induced Mean Arterial Depressor Response in Hypertensive Rats

Article

Full-text available

Jun 2015

Simulating bidirectional peripheral neural interfaces in EIDORS

Conference Paper

Jul 2020

Bioelectronic neural interfaces that deliver adaptive therapeutic stimulation in an intelligent manner must be able to sense and stimulate activity within the same nerve. Existing minimally-invasive peripheral neural interfaces can provide a read-out of the aggregate level of activity via electrical recordings of nerve activity, but these recordings are limited in terms of their specificity. Computational simulations can provide fine-grained insight into the contributions of different neural populations to the extracellular recording, but integration of the signals from individual nerve fibers requires knowledge of spread of current in the complex (heterogenous, anisotropic) extracellular space. We have developed a model which uses the open-source EIDORS package for extracellular stimulation and recording in the pelvic nerve. The pelvic nerve is the primary source of autonomic innervation to the pelvic organs, and a prime target for electrical stimulation to treat a variety of voiding disorders. We simulated recordings of spontaneous and electrically-evoked activity using biophysical models for myelinated and unmyelinated axons. As expected, stimulus thresholds depended strongly on both fibre type and electrode-fibre distance. In conclusion, EIDORS can be used to accurately simulate extracellular recording in complex, heterogenous neural geometries.

Effect of Sheetali pranayama on cardiac autonomic function among patients with primary hypertension - A randomized controlled trial

Article

Mar 2020
Compl Ther Clin Pract

Background Sheetali pranayama is a cooling pranayama practiced for hypertension (HTN). The effects of Sheetali pranayama, as a solitary intervention on cardiovascular and autonomic changes in hypertension is unknown. Materials and methods The current study was conducted on 100 patients with HTN, randomly allocated to HTN with pranayama (Intervention group,n = 50) and HTN without pranayama (control group,n = 50) group. The intervention group practiced Sheetali pranayama for a period of 3 months. Blood pressure and HRV was assessed before and after the intervention. Results Intervention group showed a significant (P < 0.05) reduction in blood pressure variables when compared to the control group. In short term HRV, time and frequency domain parameters showed parasympathetic dominance (P < 0.05) in the intervention group. Conclusion Sheetali pranayama significantly reduces blood pressure in patients with HTN and improved heart rate variability. Sheetali pranayama could thus be practiced in addition to regular medications for the efficacious management of HTN.

Baroreflex stimulation for treating resistant hypertension: ready for the prime-time?

Article

Full-text available

May 2019

The search of alternative methods for improving clinical management and outcomes of individuals affected by resistant hypertension has become a true health priority. In this review, we aimed at providing a timely overview and evidence synthesis on baroreflex activation therapy (BAT) and endovascular baroreflex amplification (EBA), two device-based therapies which rely on the principle of lowering blood pressure by stimulating the carotid baroreflex to decrease the sympathetic and enhance the parasympathetic activity. In resistant forms of arterial hypertension, accruing evidence has confirmed the capacity of these techniques to improve blood pressure control and to reduce the amount of anti-hypertensive therapy at cost of few side effects. Future results from ongoing randomized sham-controlled trials are eagerly awaited to best define the efficacy, safety and durability of effects in the long term before such an invasive approach may be considered as a suitable option in daily clinical practice. © 2018 Bolignano et al. Published by IMR press. All rights reserved.

Device-Based Neuromodulation for Resistant Hypertension Therapy

Article

Mar 2019

Despite availability of effective drugs for hypertension therapy, significant numbers of hypertensive patients fail to achieve recommended blood pressure levels on ≥3 antihypertensive drugs of different classes. These individuals have a high prevalence of adverse cardiovascular events and are defined as having resistant hypertension (RHT) although nonadherence to prescribed antihypertensive medications is common in patients with apparent RHT. Furthermore, apparent and true RHT often display increased sympathetic activity. Based on these findings, technology was developed to treat RHT by suppressing sympathetic activity with electrical stimulation of the carotid baroreflex and catheter-based renal denervation (RDN). Over the last 15 years, experimental and clinical studies have provided better understanding of the physiological mechanisms that account for blood pressure lowering with baroreflex activation and RDN and, in so doing, have provided insight into which patients in this heterogeneous hypertensive population are most likely to respond favorably to these device-based therapies. Experimental studies have also played a role in modifying device technology after early clinical trials failed to meet key endpoints for safety and efficacy. At the same time, these studies have exposed potential differences between baroreflex activation and RDN and common challenges that will likely impact antihypertensive treatment and clinical outcomes in patients with RHT. In this review, we emphasize physiological studies that provide mechanistic insights into blood pressure lowering with baroreflex activation and RDN in the context of progression of clinical studies, which are now at a critical point in determining their fate in RHT management.

Role of the Heart in Blood Pressure Lowering During Chronic Baroreflex Activation: Insight from an in Silico Analysis

Article

Full-text available

Jul 2018

Electrical stimulation of the baroreflex chronically suppresses sympathetic activity and arterial pressure and is currently being evaluated for the treatment of resistant hypertension. The antihypertensive effects of baroreflex activation are often attributed to renal sympathoinhibition. However, baroreflex activation also decreases heart rate, and robust blood pressure lowering occurs even after renal denervation. Because controlling renal sympathetic nerve activity and cardiac autonomic activity cannot be achieved experimentally, we used an established mathematical model of human physiology (HumMod) to provide mechanistic insight into their relative and combined contributions to the cardiovascular responses during baroreflex activation. Three week responses to baroreflex activation closely mimicked experimental observations in dogs including decreases in blood pressure, heart rate, and plasma norepinephrine, and increases in plasma atrial natriuretic peptide, providing validation of the model. Simulations showed that baroreflex-induced alterations in cardiac sympathetic and parasympathetic activity lead to sustained depression of cardiac function and increased secretion of atrial natriuretic peptide. Increased atrial natriuretic peptide and suppression of renal sympathetic nerve activity both enhanced renal excretory function and accounted for most of the chronic blood pressure lowering during baroreflex activation. However, when suppression of renal sympathetic nerve activity was blocked, the blood pressure response to baroreflex activation was not appreciably impaired due to inordinate fluid accumulation and further increases in atrial pressure and atrial natriuretic peptide secretion. These simulations provide a mechanistic understanding of experimental and clinical observations showing that baroreflex activation effectively lowers blood pressure in subjects with previous renal denervation.

The Role of the Vagus Nerve in Cancer Prognosis: A Systematic and a Comprehensive Review

Article

Full-text available

Jul 2018

This article reviews the role of the vagus nerve in tumor modulation and cancer prognosis. We present a systematic review of 12 epidemiological studies examining the relationship between heart rate variability, the main vagus nerve index, and prognosis in cancer patients (survival and tumor markers). These studies show that initially high vagal nerve activity predicts better cancer prognosis, and, in some studies, independent of confounders such as cancer stage and treatments. Since the design of the epidemiological studies is correlational, any causal relationship between heart rate variability and cancer prognosis cannot be inferred. However, various semi-experimental cohort studies in humans and experimental studies in animals have examined this causal relationship. The second part of this paper presents a comprehensive review including human and animal cohort and experimental studies showing that vagotomy accelerates tumor growth, while vagal nerve activation improves cancer prognosis. Based on all reviewed studies, it is concluded that the evidence supports a protective role of the vagus nerve in cancer and specifically in the metastatic stage.

Possible Breathing Influences on the Control of Arterial Pressure After Sino-aortic Denervation in Rats

Article

Full-text available

Jan 2018
Curr Hypertens Rep

Purpose of review: Surgical removal of the baroreceptor afferents [sino-aortic denervation (SAD)] leads to a lack of inhibitory feedback to sympathetic outflow, which in turn is expected to result in a large increase in mean arterial pressure (MAP). However, few days after surgery, the sympathetic nerve activity (SNA) and MAP of SAD rats return to a range similar to that observed in control rats. In this review, we present experimental evidence suggesting that breathing contributes to control of SNA and MAP following SAD.The purpose of this review was to discuss studies exploring SNA and MAP regulation in SAD rats, highlighting the possible role of breathing in the neural mechanisms of this modulation of SNA. Recent findings: Recent studies show that baroreceptor afferent stimulation or removal (SAD) results in changes in the respiratory pattern. Changes in the neural respiratory network and in the respiratory pattern must be considered among mechanisms involved in the modulation of the MAP after SAD.

Barorezeptorakivierungstherapie bei therapierefraktärer Hypertonie: Indikation und Patientenselektion: Empfehlungen der BAT-Konsensusgruppe 2017

Article

Aug 2017

Zur Behandlung der therapierefraktären Hypertonie (trHTN) steht seit einigen Jahren die Möglichkeit der Barorezeptoraktivierungstherapie (BAT) zur Verfügung. Das Verfahren wird derzeit in Deutschland an einer begrenzten Anzahl von Standorten durchgeführt, auch mit dem Ziel, eine hohe Expertise durch ausreichende Erfahrung anzubieten. Durch eine wachsende Zahl von Patienten, die mit einer BAT behandelt werden, treten jedoch im ärztlichen Alltag immer wieder Probleme im Umgang mit diesen Patienten auf. Um diese Probleme zu adressieren, wurde im November 2016 eine Konsensuskonferenz mit Experten auf dem Gebiet der trHTN durchgeführt, die die aktuellen Evidenzen und Erfahrungen, aber auch Problembereiche im Umgang mit BAT-Patienten zusammenfasst.

Insights into Pathophysiology of Carotid Baroreceptor Stimulation as a Method for Treatment of Resistant Hypertension

Article

Jan 2013

Branko Lovica

Resistant hypertension is the term used for patients who are tolerant to a maximum of three doses of antihypertensive drugs, where one of them is a diuretic. Resistant hypertension also applies to patients who are unable to reach the target blood pressure. Patients with resistant hypertension are at a higher risk of cardiovascular morbidity and mortality than those whose hypertension is controlled well. Evidence suggests that baroreceptors play an important role in a long-term blood pressure regulation. Previous studies in animals and humans have demonstrated safe and effective blood pressure decrease with chronic electrical stimulation of the carotid sinus. Electrical baroreflex stimulation appears safe and effective and may be a useful adjunct to medical treatment in patients with resistant hypertension. This review discusses the evolution and patophysiological basis of carotid baroreceptor stimulation as well as the current data available from ongoing trials.

Blood pressure after blinded, randomized withdrawal, and resumption of baroreceptor-activating therapy

Article

Mar 2017

Background: Baroreceptor-activating therapy (BAT) has been shown to control resistant hypertension in one sham-controlled and further observational studies. Incremental but significant reincrease of blood pressure (BP) have been described after open-label temporary withdrawal of such therapy. Method: Our study in 16 randomized patients investigated the course of automated office, ambulatory, and home BP in a randomized, controlled cross-over design. Results: After 4 weeks of blinded and randomized withdrawal in hypertension-controlled long-term carriers of BAT (2.67 ± 1.3 years, 145/104 mmHg), the primary end point of 35 mmHg difference, similar to initial BP drop after BAT initiation, was not reached in any patient. Ambulatory BP rose significantly during BAT off by 10/8 ± 4/3 mmHg (3.13/2.10, P = 0.007/0.002) and automated office BP by 10/4 ± 2/1 (4.17/0.58, P = 0.005/0.03) at 4 weeks after BAT on while mean home BP did not change significantly by 2/2 ± 3/2 mmHg (-5.9/-3.5, P = 0.6/0.5). Conclusion: Our data in a limited study population show, that BP rise after temporary BAT withdrawal is significant but does not reach a magnitude comparable with the initial drop after de novo implantation. Such results points to preserved hypertension control after electrical BAT withdrawal and deserves further pathophysiological and clinical clarification.

Autonomic Neuromodulation through Devices for Hypertension

Article

Dec 2016

Beneficial effects of prolonged blood pressure control after carotid artery stenting

Article

Full-text available

Jan 2017

Objectives The main purpose of this study was to investigate whether carotid artery stenting (CAS) plus medicine in patients with severe carotid artery stenosis provide a better long-term blood pressure (BP) control compared to other medical treatments alone. The other aim was to explore the correlation between post-CAS hypotension within 6 h and long-term BP reductions after CAS. Materials and methods Patients with severe carotid stenosis were recruited either in the CAS group or in the medication group. BPs and the number of classes of antihypertensive agents were recorded at baseline, 6, and 12 months. Extra BP information was collected at 6 h, 3 days, and 1 month after CAS. Univariate and multivariate linear regressions were performed to test the relationship of BP changes among CAS and medication groups after 6 and 12 months of follow-up. Univariate linear regressions were also used to determine the correlations between the mean or maximal systolic BP (SBP) reductions at 6 h and 1 year post-CAS. Results In total, 72 members in the CAS group and 82 members in the medication group were recruited. Compared with the medication group, patients in the CAS group had greater BP reductions at 6 and 12 months of follow-up after adjusting for confounding factors (13.56 mmHg at 6 months, P=0.0002; 16.98 mmHg at 12 months, P<0.0001). This study also shows significant positive correlations between the mean or maximal SBP reductions 6 h post-CAS and SBP reductions 1 year post-CAS (β =0.20±0.07, P=0.0067 and β =0.47±0.10, P<0.0001, respectively). Conclusion As compared to medical treatment alone, CAS may provide significant beneficial effect on long-term BP control 1 year post-CAS. Furthermore, SBP reductions 6 h post-CAS may predict the SBP reductions 1 year post-CAS.

Baroreflex activation therapy in patients with heart failure and a reduced ejection fraction: Long-term outcomes

Article

Apr 2024
EUR J HEART FAIL

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.

Baroreflex Activation Therapy in Patients with Heart Failure with a Reduced Ejection Fraction

Article

Jun 2023
Heart Fail Clin

New Approaches to Pathogenesis and Management of Hypertension

Article

Dec 2009

Immediate effects of the practise of Sheethali pranayama on heart rate and blood pressure parameters in healthy volunteers

Article

May 2021
J Compl Integr Med

Objectives: Sheetali pranayama, a cooling pranayama is best known for its calming and relaxing nature, widely used for many conditions like depression, anxiety and hypertension. The aim of the study was to evaluate the immediate effect of the practice of Sheetali pranayama on heart rate and blood pressure parameters in healthy volunteers. Methods: Apparently, 60 healthy volunteers were involved, from both sexes. They were split into pranayama (n=30) and control (n=30) groups at random. Sheetali pranayama was performed for 5 min (5 cycles) in the pranayama group and normal breathing (12-16 breaths/min) was permitted in the control group. Heart rate (HR) and blood pressure (BP) were recorded with RMS polyrite in the supine position after 5 min of rest. Results: The HR in the pranayama group significantly decreased (p=0.04). Systolic (SBP) and diastolic blood (DBP) pressure, pulse pressure (PP) and mean arterial pressure (MAP) decreased significantly (p<0.05) relative to control after pranayama practice. Pre-Post inter-group results has also shown that the pranayama group has substantially decreased HR and BP indices. Conclusions: Present study shows that the practice of Sheetlai pranayama creates a relaxed state, and parasympathetic activity overrides sympathetic activity in this state. It indicates that in healthy volunteers, pranayama strengthens the resting cardiovascular parameters.

Benefits of pharmacological and electrical cholinergic stimulation in hypertension and heart failure

Article

Apr 2021

Systemic arterial hypertension and heart failure are cardiovascular diseases that affect millions of individuals worldwide. They are characterized by a change in the autonomic nervous system balance, highlighted by an increase in sympathetic activity associated with a decrease in parasympathetic activity. Most therapeutic approaches seek to treat these diseases by medications that attenuate sympathetic activity. However, there is a growing number of studies demonstrating that the improvement of parasympathetic function, by means of pharmacological or electrical stimulation, can be an effective tool for the treatment of these cardiovascular diseases. Therefore, this review aims to describe the advances reported by experimental and clinical studies that addressed the potential of cholinergic stimulation to prevent autonomic and cardiovascular imbalance in hypertension and heart failure. Overall, the published data reviewed demonstrate that the use of central or peripheral acetylcholinesterase inhibitors is efficient to improve the autonomic imbalance and hemodynamic changes observed in heart failure and hypertension. Of note, the baroreflex and the vagus nerve activation have been shown to be safe and effective approaches to be used as an alternative treatment for these cardiovascular diseases. In conclusion, pharmacological and electrical stimulation of the parasympathetic nervous system has the potential to be used as a therapeutic tool for the treatment of hypertension and heart failure, deserving to be more explored in the clinical setting.

HRT assessment reviewed: A systematic review of Heart Rate Turbulence methodology

Article

Full-text available

Jun 2020

Heart rate turbulence (HRT) is a biphasic reaction to a ventricular premature contraction (VPC) mainly mediated by the baroreflex. It can be used for risk stratification in different disease patterns. Despite existing standards there is a lot of variation in terms of measuring and calculating HRT, which complicates research and application. Objective: This systematic review outlines and evaluates the methodological spectrum of HRT research, especially filtering criteria, parameter calculation and thresholds. Approach: The analysis includes all research papers written in English that have been published before 12.10.2018, are listed on PubMed and involve calculation of HRT parameter values. Main results: HRT assessment is still being performed in various ways and important specifications of the methodology are not given in many articles. Nevertheless, some suggestions regarding HRT methodology can be made: A normalised turbulence slope should be used to uncouple the parameter from heart rate and frequency of extrasystoles. Filtering criteria as formerly reviewed in the guidelines should be met and mentioned. The minimal number of VPCSs as well as new cut-off values for different risks need to be further evaluated. Most importantly, the exact and complete methodology must be described to ensure reproducibility and comparability. Significance: Methodical variation hinders comparability of research and medical application. Our continuing questions help to further standardise the measurement and calculation of HRT and increase its value for medical risk stratification.

Electrical stimulation of the carotid sinus lowers arterial pressure and improves heart rate variability in L-NAME hypertensive conscious rats

Article

May 2020

We evaluated the effects of long-term (48 h) electrical stimulation of the carotid sinus (CS) in hypertensive rats. l-NAME-treated (10 days) Wistar rats were implanted with a catheter in the femoral artery and a miniaturized electrical stimulator attached to electrodes positioned around the left CS, encompassing the CS nerve. One day after implantation, arterial pressure (AP) was directly recorded in conscious animals for 60 min. Square pulses (1 ms, 3 V, 30 Hz) were applied intermittently (20/20 s ON/OFF) to the CS for 48 h. After the end of stimulation, AP was recorded again. Nonstimulated rats (control group) and rats without electrodes around the CS (sham-operated) were also studied. Next, the animals were decapitated, and segments of mesenteric resistance arteries were removed to study vascular function. After the stimulation period, AP was 16 ± 5 mmHg lower in the stimulated group, whereas sham-operated and control rats showed similar AP between the first and second recording periods. Heart rate variability (HRV) evaluated using time and frequency domain tools and a nonlinear approach (symbolic analysis) suggested that hypertensive rats with electrodes around the CS, stimulated or not, exhibited a shift in cardiac sympathovagal balance towards parasympathetic tone. The relaxation response to acetylcholine in endothelium-intact mesenteric arteries was enhanced in rats that underwent CS stimulation for 48 h. In conclusion, long-term CS stimulation is effective in reducing AP levels, improving HRV and increasing mesenteric vascular relaxation in l-NAME hypertensive rats. Moreover, only the presence of electrodes around the CS is effective in eliciting changes in HRV similar to those observed in stimulated rats.

Device-based therapies for arterial hypertension

Article

Apr 2020

Arterial hypertension is the most prevalent modifiable risk factor associated with cardiovascular morbidity and mortality. Although antihypertensive drugs are widely available, in many patients blood pressure control to guideline-recommended target values is not achieved. Several device-based approaches have been introduced to lower blood pressure; most of these strategies aim to modulate autonomic nervous system activity. Clinical trials have moved from including patients with resistant hypertension receiving intensive pharmacological treatment to including patients with mild-to-moderate hypertension in the presence or absence of antihypertensive medications. Renal sympathetic denervation is the most extensively investigated device-based therapy for hypertension, and randomized, sham-controlled trials have provided proof-of-principle data for its blood pressure-lowering efficacy. Unilateral electrical baroreflex activation, endovascular baroreflex amplification and pacemaker-mediated cardiac neuromodulation therapy have yielded promising results in observational trials, which need to be confirmed in larger, adequately powered, sham-controlled trials. Until further evidence becomes available, device-based therapy for hypertension should not be considered for routine treatment. However, when considering a device-based treatment for hypertension, the underlying pathophysiology in each patient has to be taken into consideration, and the procedural risks weighed against the cardiovascular risk attributable to the elevated blood pressure. This Review summarizes the pathophysiological rationale and the latest clinical evidence for device-based therapies for hypertension.

Endovascular Baroreflex Amplification for Resistant Hypertension: What You Need to Know

Article

Feb 2020

Endovascular baroreflex amplification is an alternative treatment strategy for patients with resistant hypertension. In endovascular baroreflex, the carotid baroreflex is activated by a MobiusHD ® device (MD) which has been implanted in the internal carotid artery. This review will discuss the MD technology and mechanism of action and promising results in the first-in-human prospective study involving the use of the MD in patients with resistant hypertension.

Smart Baroreceptor Activation Therapy Strikingly Attenuates Blood Pressure Variability in Hypertensive Rats With Impaired Baroreceptor

Article

Dec 2019

Increased blood pressure (BP) variability (BPV) is an independent risk factor of cardiovascular events among hypertensive patients. The arterial baroreceptor reflex is a powerful regulator of BP and attenuates BPV via a sympathetic negative feedback control. Conventional baroreceptor activation therapy (cBAT) electrically stimulates the carotid baroreceptors with constant stimulation parameters. While cBAT lowers BP, it does not mount a pressure feedback mechanism. We hypothesized that baroreceptor activation therapy with a pressure feedback system (smart BAT [sBAT]) is able to reduce BPV as well as lower BP. We developed sBAT that electrically stimulated baroreceptors at a frequency proportional to the difference between instantaneous BP and a preset reference pressure, and compared its performance with cBAT. In 14-week-old spontaneously hypertensive rats (n=6), we implanted BP telemeter and created impaired arterial baroreceptors by modified sino-aortic denervation. One week after surgical preparation, we administered sBAT, cBAT or no stimulation (sham) for 15 minutes and compared BP and BPV under freely moving condition. Both cBAT and sBAT significantly lowered mean BP (sham, 141.3±12.8; cBAT, 114.3±11.4; and sBAT, 112.0±7.3 mm Hg). Conventional BAT did not affect BPV at all, while sBAT significantly reduced BPV (sham, 15.4±2.6; cBAT, 16.0±5.2; and sBAT, 9.7±3.3 mm Hg). sBAT also prevented transient excessive BP rise and fall. In conclusion, sBAT was capable of reducing BP and attenuating BPV in hypertensive rats with impaired baroreceptor. sBAT is a novel treatment option for hypertensive patients with increased BPV.

Anatomische und prozedurale Determinanten einer Blutdruckreduktion nach kathetergestützter renaler Denervation bei Patienten mit therapieresistenter Hypertonie

Thesis

Jan 2018

Lucas Lauder

Carotid Baroreceptor Stimulation

Chapter

Jan 2019

Baroreflex activation through electrical carotid sinus stimulation has been developed for resistant arterial hypertension and heart failure management. Electrical carotid sinus stimulation lowered blood pressure in various hypertensive animal models and improved cardiac remodeling and survival in experimental heart failure. In human mechanistic profiling studies, electrical carotid sinus stimulation was shown to lower blood pressure through sympathetic inhibition; however, the response showed substantial interindividual variability. The first-generation device reduced blood pressure in controlled and uncontrolled clinical trials. Controlled clinical trials proving efficacy in blood pressure reduction do not exist for the currently available second-generation carotid sinus stimulator. Investigations in heart failure patients showed symptomatic improvements; however, echocardiography measurements did not change significantly. Overall, electrical carotid sinus stimulation is a promising approach. Yet, data from properly controlled trials is required before introducing electrical carotid sinus stimulation in clinical routine.

Effets bénéfiques de l’activité physique dans le syndrome d’apnées-hypopnées obstructives du sommeil

Thesis

Full-text available

May 2018

Mathieu Berger

L’objectif de ce travail de thèse était d’évaluer le bénéfice d’une activité physique régulière sur le syndrome d’apnées-hypopnées obstructives du sommeil (SAHOS). Pour répondre à notre objectif, cinq études ont été conduites pendant cette thèse et seront présentées au cours de ce manuscrit. Ces études se sont déroulées dans deux contextes de pratique distincts : un contexte associatif au sein de la Fédération Française d’Éducation Physique et de Gymnastique Volontaire (FFEPGV) et un contexte hospitalier au sein de l’Unité de réhabilitation cardio-respiratoire du CHU de Saint-Etienne. Notre étude principale, l’étude EXESAS, a évalué le bénéfice d’un programme d’activité physique pratiqué au sein de la FFEPGV (programme NeuroGyV™) dans une étude contrôlée randomisée incluant 96 patients avec un SAHOS modéré et âgés de 40 à 80 ans. Nous avons montré que neuf mois de ce programme, incluant trois heures d’activité physique par semaine, permettait de « guérir » 58% des patients du groupe exercice alors que seulement 20% des patients du groupe contrôle ayant bénéficié de conseils diététiques et de recommandations de bonne pratique en activité physique étaient considérés comme guéris (index d’apnées-hypopnées [IAH] < 15 évènements/heure). A l’issue du programme, les patients du groupe exercice amélioraient également leur qualité de vie et réduisaient leur somnolence. Au-delà de l’amélioration de l’IAH, nous avons mis en évidence une augmentation de la consommation maximale d’oxygène, suggérant une réduction du risque cardiovasculaire. L’étude EXESAS s’est par ailleurs intéressée à l’effet du programme NeuroGyV™ sur l’activité du système nerveux autonome (SNA) mesurée par la variabilité de fréquence cardiaque (VFC). Il a été montré que l’activité du SNA était préservée chez les patients SAHOS ayant bénéficié du programme d’activité physique. En revanche, le groupe contrôle présentait quant à lui une charge hypoxémique plus importante et une variabilité de fréquence cardiaque diminuée, suggérant que le SAHOS et le risque cardiovasculaire associé s’aggravaient spontanément en l’absence d’une activité physique régulière. Le screening de l’étude EXESAS a permis de réaliser un abstract sur le choix du questionnaire de dépistage du SAHOS le plus pertinent en population générale. Nous avons alors montré que le questionnaire STOP-BANG avait une meilleure sensibilité que le questionnaire de Berlin et qu’il devrait être privilégié en dépistage clinique même si sa spécificité reste faible.Enfin, nos travaux de recherche en réhabilitation cardiaque ont permis de confirmer le bénéfice du réentrainement à l’effort sur la sévérité du SAHOS et le rééquilibrage du SNA chez des patients coronariens. Par contre, les résultats préliminaires de l’étude RICAOS ont révélé que le renforcement des muscles inspiratoires chez les patients coronariens souffrant d’un SAHOS modéré n’apportait pas de bénéfice supplémentaire par rapport à un programme de réhabilitation cardiaque classique.En conclusion, l’activité physique régulière réduit efficacement la sévérité du SAHOS chez des patients avec ou sans antécédents cardiaques. Les résultats des différentes études conduites au cours de cette thèse suggèrent que l’activité physique régulière devrait être considérée comme une pierre angulaire dans la prévention et dans la prise en charge des formes légères et modérées. De futurs études devraient être conduites afin d’explorer plus en détail les mécanismes physiologiques sous-jacents et déterminer quels patients doivent bénéficier en priorité de cette alternative thérapeutique.

Baroreflexaktivierungstherapie bei therapieresistenter Hypertonie: Empfehlungen der BAT-Konsensusgruppe zu Implantation und Nachsorge

Article

Jan 2019

Die Hemmung eines erhöhten Sympathikotonus stellt für verschiedene Erkrankungen ein effektives und in vielen Fällen kausales Therapieprinzip dar. Neben pharmakologischen Ansätzen mit Betablockern oder zentralen Sympatholytika sind in den letzten Jahren zunehmend auch interventionelle Verfahren, wie die renale Sympathikusdenervation oder die Baroreflexaktivierungstherapie (BAT) v. a. in der Behandlung der therapierefraktären arteriellen Hypertonie zur Anwendung gekommen. Kontroverse Studienergebnisse zur Wirksamkeit dieser Verfahren haben jedoch die Diskussion um Patientenselektion und Qualitätsstandards in der Anwendung entfacht. Infolge der aktuellen Indikationserweiterung findet zudem die BAT zunehmend Verbreitung in der Behandlung der systolischen Herzinsuffizienz. Eine Gruppe führender Anwender und Wissenschaftler auf dem Gebiet der BAT hat daher zusammen mit interdisziplinären Hypertensiologen in einer Konsensuskonferenz Voraussetzungen für die Etablierung eines BAT-Programms und Standards zur Implantation, Programmierung und Nachsorge definiert.

Interaction between baroreflex and chemoreflex in the cardiorespiratory responses to stimulation of the carotid sinus/nerve in conscious rats

Article

Dec 2018
AUTON NEUROSCI-BASIC

Electrical stimulation of the carotid baroreflex has been thoroughly investigated for treating drug-resistant hypertension in humans. However, a previous study from our laboratory, performed in conscious rats, has demonstrated that electrical stimulation of the carotid sinus/nerve (CS) activated both the carotid baroreflex as well as the carotid chemoreflex, resulting in hypotension. Additionally, we also demonstrated that the carotid chemoreceptor deactivation potentiated this hypotensive response. Therefore, to further investigate this carotid baroreflex/chemoreflex interaction, besides the hemodynamic responses, we evaluated the respiratory responses to the electrical stimulation of the CS in both intact (CONT) and carotid chemoreceptors deactivated (CHEMO-X) conscious rats. CONT rats showed increased ventilation in response to electrical stimulation of the CS as measured by the respiratory frequency (fR), tidal volume (VT) and minute ventilation (VE), suggesting a carotid chemoreflex activation. The carotid chemoreceptor deactivation abolished all respiratory responses to the electrical stimulation of the CS. Regarding the hemodynamic responses, the electrical stimulation of the CS caused hypotensive responses in CONT rats, which were potentiated by the carotid chemoreceptors deactivation. Heart rate (HR) responses did not differ between groups. In conclusion, the present study showed that the electrical stimulation of the CS, in conscious rats, activates both the carotid baroreflex and the carotid chemoreflex driving an increase in ventilation and a decrease in AP. These findings further contribute to our understanding of the electrical stimulation of CS.

Obstructive Sleep Apnea in Cardiac Rehabilitation Patients

Article

Jul 2018

Study objectives: Although regular physical activity improves obstructive sleep apnea (OSA) in the general population, this finding has not been assessed in postmyocardial infarction (MI) patients in a rehabilitation setting (coronary artery disease, CAD). We aimed to determine whether cardiac rehabilitation may benefit post-MI patients in terms of OSA disease and associated autonomic nervous system (ANS) activity. Methods: Consecutive post-MI patients participating in the ambulatory cardiac rehabilitation program of St-Etienne University Hospital were included in this study. The apnea-hypopnea index calculated from electrocardiogram (ECG)-derived respiration (AHIEDR) was obtained through nocturnal Holter ECG recordings. According to AHIEDR, patients were classified as normal, mild, moderate, or severe OSA (< 5, 5-14, 15-29, ≥ 30, respectively). Physiological performance (peak VO2) was established via cardiopulmonary exercise testing. ANS activity was evaluated through spontaneous baroreflex sensibility as well as heart rate variability analysis. Results: Of the 105 patients with CAD and OSA included (95 men, 55.2 ± 12.4 years), 100 had at least 1 cardiovascular risk factor (98%) and 52 patients (50%) had an ANS dysfunction. Surprisingly, 68 of these patients with OSA (65%) were free of classical diurnal symptoms usually associated with sleep apnea. In response to cardiac rehabilitation, AHIEDR decreased significantly (-9.3 ± 9.5, P < .0001) only in patients with severe OSA, and the decrease was even greater when peak VO2 and baroreflex sensibility improved beyond 20% compared to basal values (-11.6 ± 9.1, P < .001). Conclusions: Severe OSA in patients with CAD is significantly improved after 2 months of cardiopulmonary rehabilitation. Reviving ANS activity through physical activity might be a target for complementary therapy of OSA in patients with CAD.

Efficacy and safety of baroreflex activation therapy for treatment of resistant hypertension: a systematic review and meta-analysis

Article

Apr 2018

To provide definite evidence for the anti-hypertensive benefit of Baroreflex Activation Therapy (BAT) for resistant hypertension, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of BAT. Electronic searches were conducted in PubMed, EMBASE, The Cochrane Library and Web of Science. Two reviewers independently determined the eligibility of studies and extracted the data. The quality of all included studies was evaluated by the use of the Newcastle Ottawa Scale (NOS). Disagreements were settled through discussion. Twelve studies, included one randomized clinical trials (RCTs) and eleven prospective studies were eligible for qualitative analysis and five prospective studies were selected for meta-analysis. The data of analysis showed office systolic blood pressure (SBP)(WMD = −24.01, 95% CI = −28.65 to −19.36, P= 0.753I² = 0.0%) and diastolic blood pressure (DBP)(WMD = −12.53, 95% CI = −15.82 to −9.24,P = 0.893,I² = 0.893) decreased by BAT treatment.The effect on SBP was both significant in the Barostim neo TM device (WMD = −22.49, 95% CI = −29.13 to 15.84, P= 0.443; I² = 0.0%) and Rheos System (WMD = 25.46, 95% CI = −31.96 to −18.96, P= 0.703; I² = 0.0%). Our study found office BP were significantly decreased by BAT treatment, but available evidence is limited by risk of bias, small sample size, and few RCTs. Thus, there is presently insufficient evidence to fully evaluate the efficacy and safety of BAT for Patients with Resistant Hypertension. Additional high-quality RCT research with long-term follow-up is required.

Baroreceptor Stimulation

Chapter

Jan 2018

Pathogenesis of Hypertension

Chapter

Jan 2018

Tonic aortic depressor nerve stimulation does not impede baroreflex dynamic characteristics concomitantly mediated by the stimulated nerve

Article

Nov 2017
AM J PHYSIOL-REG I

Although electrical activation of the carotid sinus baroreflex (baroreflex activation therapy) is being explored as a device therapy for resistant hypertension, possible effects on baroreflex dynamic characteristics of interaction between electrical stimulation and pressure inputs are not fully elucidated. To examine whether the electrical stimulation of the baroreceptor afferent nerve impedes normal short-term arterial pressure (AP) regulation mediated by the stimulated nerve, we electrically stimulated the right aortic depressor nerve (ADN) while estimating the baroreflex dynamic characteristics by imposing pressure inputs to the isolated baroreceptor region of the right ADN in nine anesthetized rats. A Gaussian white noise signal with a mean of 120 mmHg and standard deviation of 20 mmHg was used for the pressure perturbation. A tonic ADN stimulation (2 or 5 Hz, 10 V, 0.1-ms pulse width) decreased mean sympathetic nerve activity (367.0 ± 70.9 vs. 247.3 ± 47.2 arbitrary units, P < 0.01) and mean AP (98.4 ± 7.8 vs. 89.2 ± 4.5 mmHg, P < 0.01) during dynamic pressure perturbation. The ADN stimulation did not affect the slope of dynamic gain in the neural arc transfer function from pressure perturbation to sympathetic nerve activity (16.9 ± 1.0 vs. 14.7 ± 1.6 dB/decade, not significant). These results indicate that electrical stimulation of the baroreceptor afferent nerve does not significantly impede the dynamic characteristics of the arterial baroreflex concomitantly mediated by the stimulated nerve. Short-term AP regulation by the arterial baroreflex may be preserved during the baroreflex activation therapy.

Hoffnungsvolle Therapieergänzung bei therapieresistentem Hypertonus: Barorezeptor-Stimulation

Article

Feb 2012

Trotz der Entwicklung von potenten antihypertensiven Medikamenten stellt die Behandlung der therapieresistenten Hypertonie eine große Herausforderung dar, insbesondere aufgrund assoziierter kardiovaskulärer Folgen für Patienten und der sozioökonomischen Bedeutung für das Gesundheitssystem. Aufgrund des technischen Fortschrittes konnten minimalinvasive interventionelle Verfahren entwickelt werden, deren physiologische Grundlagen bereits mehrere Jahrzehnte bekannt sind. Neben der renalen Denervation stellt die Barorezeptor-Stimulation einen innovativen Ansatz dar, auf deren Gebiet erhebliche methodische Fortschritte erzielt werden konnten. Im Rahmen von kontrollierten Studien konnte die Wirksamkeit dieses Verfahrens bei therapieresistenten Hypertonikern erfolgreich gezeigt werden. Aufgrund beschriebener möglicher prozeduraler Komplikationen und der fehlenden Langzeiterfahrungen ist allerdings eine fundierte Evaluation der Patienten mit sicherem Ausschluss sekundärer Ursachen oder der Sicherstellung einer adäquaten antihypertensiven Therapie mit ausreichender diuretischer Medikation von grundlegender Bedeutung. Dafür ist eine sehr enge und intensive Kooperation zwischen Hypertensiologen und interventionellen Angiologen eine Grundvoraussetzung, denn nur die richtige Indikationsstellung kann Grundlage für den interventionellen Erfolg sein.

ASSESSMENT OF DRUG IMPACT ON HEART RATE TURBULENCE

Article

Full-text available

Aug 2016

Heart Rate Turbulence: Standards of Measurement, Physiological Interpretation, and Clinical Use

Article

Full-text available

Nov 2008

This consensus statement has been compiled on behalf of the International Society for Holter and Noninvasive Electrophysiology. It reviews the topic of heart rate turbulence (HRT) and concentrates on technologies for measurement, physiologic background and interpretation, and clinical use of HRT. It also lists suggestions for future research. The phenomenon of HRT refers to sinus rhythm cycle-length perturbations after isolated premature ventricular complexes. The physiologic pattern of HRT consists of brief heart rate acceleration (quantified by the so-called turbulence onset) followed by more gradual heart rate deceleration (quantified by the so-called turbulence slope) before the rate returns to a pre-ectopic level. Available physiologic investigations confirm that the initial heart rate acceleration is triggered by transient vagal inhibition in response to the missed baroreflex afferent input caused by hemodynamically inefficient ventricular contraction. A sympathetically mediated overshoot of arterial pressure is responsible for the subsequent heart rate deceleration through vagal recruitment. Hence, the HRT pattern is blunted in patients with reduced baroreflex. The HRT pattern is influenced by a number of factors, provocations, treatments, and pathologies reviewed in this consensus. As HRT measurement provides an indirect assessment of baroreflex, it is useful in those clinical situations that benefit from baroreflex evaluation. The HRT evaluation has thus been found appropriate in risk stratification after acute myocardial infarction, risk prediction, and monitoring of disease progression in heart failure, as well as in several other pathologies.

Prognostic value of baroreflex testing after acute myocardial infarction

Article

Full-text available

Mar 1992
Br Heart J

Disturbances of autonomic function are recognised in both the acute and convalescent phases of myocardial infarction. Recent studies have suggested that disordered autonomic function, particularly the loss of protective vagal reflexes, is associated with an increased incidence of arrhythmic deaths. The purpose of this study was to compare the value of differing prognostic indicators with measures of autonomic function and to assess the safety of arterial baroreflex testing early after infarction. As part of a prospective trial of risk stratification in post-infarction patients arterial baroreflex sensitivity, heart rate variability, long term electrocardiographic recordings, exercise stress testing, and ejection fraction were recorded between days 7 and 10 in 122 patients with acute myocardial infarction. During a one year follow up period there were 10 arrhythmic events. Baroreflex sensitivity was appreciably reduced in these patients suffering arrhythmic events (1.73 SD (1.49) v 7.83 (4.5) ms/mm hg, 95% confidence interval (CI) 4.8 to 7.3, p = 0.0001). Significant correlations were noted with age (r = -0.68, p less than 0.001) but not left ventricular function. When baroreflex sensitivity was adjusted for the effects of age and ventricular function baroreflex sensitivity was still considerably reduced in the arrhythmic group (2.1 v 7.57 ms/mm Hg, p less than 0.0001). Depressed baroreflex sensitivity carried the highest relative risk for arrhythmic events (23.1, 95% CI 7.7 to 69.2) and was superior to other prognostic variables including left ventricular function (10.4, 95% CI 3.3 to 32.6) and heart rate variability (10.1, 95% CI 5.6 to 18.1). No major complications were noted with baroreflex testing and in particular no patients developed ischaemic or arrhythmic symptoms during the procedure. Disordered autonomic function as measured by depressed baroreflex sensitivity or reduced heart rate variability was associated with an increase incidence of arrhythmic events in post-infarction patients. Baroreflex testing can be safely performed in the immediate post-infarction period.

Heart rate spectral analysis, cardiac norepinephrine spillover, and muscle sympathetic nerve activity during human sympathetic nervous activation and failure

Article

Full-text available

Aug 1994

Although heart rate variability (HRV) at 0.1 Hz has been proposed as a noninvasive clinical measure of cardiac sympathetic nerve firing, this premise has not been sufficiently validated by comparison with techniques such as microneurography and the measurement of norepinephrine spillover from the heart that more directly reflect presynaptic sympathetic activity. We compared the three techniques under conditions of effective cardiac sympathetic denervation, pure autonomic failure (n = 4), dopamine beta-hydroxylase deficiency (n = 1), and after cardiac transplantation (n = 9) as well as in the context of sympathetic nervous activation in cardiac failure (n = 15) and with aging (n = 10). Age-matched comparisons were made in each case with healthy individuals drawn from a pool of 52 volunteers. In pure autonomic failure and early after transplantation, cardiac norepinephrine spillover was negligible, and HRV was low. Late after transplantation, however, cardiac norepinephrine spillover returned to normal levels, and HRV remained low. In comparison to younger subjects (18 to 35 years old), older individuals (60 to 75 years old) had higher muscle sympathetic nerve activity (young, 22.9 +/- 1.9; old, 31.3 +/- 5.8 bursts per minute; P < .05) and cardiac norepinephrine spillover (young, 14.3 +/- 2.5; old, 20.1 +/- 3.0 ng/min; P < .05). In contrast, total HRV was reduced by 89%, and at 0.1 Hz it was reduced by 93% (P < .05). Cardiac failure was also characterized by elevated cardiac norepinephrine spillover (cardiac failure patients, 59 +/- 4; healthy volunteers, 18 +/- 3 ng/min; P < .01) but reduced 0.1 Hz HRV (cardiac failure patients, 49 +/- 17; healthy volunteers, 243 +/- 4 ms2; P < .05). HRV at 0.1 Hz depends on factors in addition to cardiac sympathetic nerve firing rates, including multiple neural reflexes, cardiac adrenergic receptor sensitivity, postsynaptic signal transduction, and electrochemical coupling, and is not directly related to cardiac norepinephrine spillover, which is a more direct measure of the sympathetic nerve firing rate.

Long-term effects of carotid sinus denervation on arterial blood pressure in humans

Article

Full-text available

Apr 2002
CIRCULATION

After experimental carotid sinus denervation in animals, blood pressure (BP) level and variability increase markedly but normalize to preoperative levels within 10 to 14 days. We investigated the course of arterial BP level and variability after bilateral denervation of the carotid sinus baroreceptors in humans. We studied 4 women (age 41 to 63 years) who were referred for evaluation of arterial baroreflex function because of clinical suspicion of carotid sinus denervation attributable to bilateral carotid body tumor resection. The course of BP level and variability was assessed from repeated office and 24-hour ambulatory measurements (Spacelabs/Portapres) during 1 to 10 years of (retrospective) follow-up. Rapid cardiovascular reflex adjustments to active standing and Valsalva's maneuver were assessed. Office BP level increased from 132/86 mm Hg (range, 118 to 148/80 to 92 mm Hg) before bilateral surgery to 160/105 mm Hg (range, 143 to 194/90 to 116 mm Hg) 1 to 10 years after surgery. During continuous 24-hour noninvasive BP recording (Portapres), a marked BP variability was apparent in all 4 patients. Initial symptomatic hypotension on change to the upright posture and abnormal responses to Valsalva's maneuver were observed. Acute carotid sinus denervation, as a result of bilateral carotid body tumor resection, has a long-term effect on the level, variability, and rapid reflex control of arterial BP. Therefore, in contrast to earlier experimental observations, the compensatory ability of the baroreceptor areas outside the carotid sinus seems to be of limited importance in the regulation of BP in humans.

Heart Rate Variability: Measurement and Clinical Utility

Article

Full-text available

Feb 2005

Electrocardiographic RR intervals fluctuate cyclically, modulated by ventilation, baroreflexes, and other genetic and environmental factors that are mediated through the autonomic nervous system. Short term electrocardiographic recordings (5 to 15 minutes), made under controlled conditions, e.g., lying supine or standing or tilted upright can elucidate physiologic, pharmacologic, or pathologic changes in autonomic nervous system function. Long-term, usually 24-hour recordings, can be used to assess autonomic nervous responses during normal daily activities in health, disease, and in response to therapeutic interventions, e.g., exercise or drugs. RR interval variability is useful for assessing risk of cardiovascular death or arrhythmic events, especially when combined with other tests, e.g., left ventricular ejection fraction or ventricular arrhythmias.

An Implantable Carotid Sinus Baroreflex Activating System: Surgical Technique and Short-Term Outcome from a Multi-Center Feasibility Trial for the Treatment of Resistant Hypertension

Article

Full-text available

May 2007
EUR J VASC ENDOVASC

To assess perioperative outcomes and blood pressure (BP) responses to an implantable carotid sinus baroreflex activating system being investigated for the treatment of resistant hypertension. We report on the first seventeen patients enrolled in a multicenter study. Bilateral perivascular carotid sinus electrodes (CSL) and a pulse generator (IPG) are permanently implanted. Optimal placement of the CSL is determined by intraoperative BP responses to test activations. Acute BP responses were tested postoperatively and during the first four months of follow-up. Prior to implant, BP was 189.6+/-27.5/110.7+/-15.3 mmHg despite stable therapy (5.2+/-1.8 antihypertensive drugs). The mean procedure time was 202+/-43 minutes. No perioperative strokes or deaths occurred. System tests performed 1 or up to 3 days postoperatively resulted in significant (all p < or = 0.0001) mean maximum reduction, with standard deviations and 95% confidence limits for systolic BP, diastolic BP and heart rate of 28+/-22 (17, 39) mmHg, 16+/-11 (10, 22) mmHg and 8+/-4 (6, 11) BPM, respectively. Repeated testing during 3 months of therapeutic electrical activation demonstrated a durable response. These preliminary data suggest an acceptable safety of the procedure with a low rate of adverse events and support further clinical development of baroreflex activation as a new concept to treat resistant hypertension.

Acute Device-Based Blood Pressure Reduction: Electrical Activation of the Carotid Baroreflex in Patients Undergoing Elective Carotid Surgery

Article

Full-text available

Apr 2007

Carotid sinus baroreceptors are involved in controlling blood pressure (BP) by providing input to the cardiovascular regulatory centers of the medulla. The acute effect of temporarily placing an electrode on the carotid sinus wall to electrically activate the baroreflex was investigated. We studied 11 patients undergoing elective carotid surgery. Baseline BP was 146+30/66+/-17 mm Hg and heart rate (HR) 72+/-7 bpm (mean +/- standard deviation). An electrode was placed upon the carotid sinus and after obtaining a steady state baseline of BP and HR, an electric current was applied and increased in 1-volt increments. A voltage dependent and highly significant reduction in BP was observed which averaged 18+/-26* and 8.0+/-12 mm Hg for systolic BP and diastolic BP, respectively. Maximal reductions occurred at 4.4+/-1.2 V: 23+/-24 mm Hg*, 16+/-10 mm Hg* and 7+/-12 bpm* for systolic BP, diastolic BP and HR, respectively ( = p <.05). Thus, electrical stimulation of the carotid sinus activates the carotid baroreflex resulting in a reduction in BP and HR. This presents a proof of concept for device based baroreflex modulation in acute BP regulation and adds to the available data which provide a rationale for evaluating this system in the context of chronic BP reduction in hypertensive patients.

Heart rate variability: Standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology

Article

Jan 1996

Heart rate variability. Standards of measurement, physiological interpretation, and clinical use Eur Heart J Electrophysiology TFESCNASP 1996 17 3 354 381 8737210

Article

Mar 1996

PLASMA RENIN ACTIVITY DURING HYPOTENSIVE RESPONSES TO ELECTRICAL STIMULATION OF CAROTID SINUS NERVES IN CONSCIOUS DOGS

Article

Jan 1994
CLIN EXP PHARMACOL P

1. The interaction of electrical stimulation of the carotid sinus nerves (carotid sinus nerve stimulation, CSNS) with mechanisms of renin release was studied in conscious and unrestrained resting beagle dogs receiving a standardized diet (sodium intake, 4.5 mmol/kg bodyweight (bw); water intake, 91 mL/kg bw). 2. By CSNS, mean arterial blood pressure (MAP) was lowered for periods of 20 min to levels between 101 ± 4 and 56 ± 5 mmHg. 3. In another group of conscious dogs, renal perfusion pressure (RPP) was lowered to 95 ± 4 mmHg for periods of 20 min by partial suprarenal aortic occlusion in order to assess the influence of a reduced RPP on plasma renin activity (PRA) without concomitant CSNS. 4. During CSNS, PRA increased markedly (> 100%) only when MAP was reduced below 75 mmHg. 5. With aortic constriction and an RPP of 95 mmHg, the increase in PRA was 955%, which is more than three‐fold higher than the increase in PRA during CSNS at MAP levels <65 mmHg (314%). 6. The observed responses indirectly support the hypothesis that basal activity in efferent renal nerve discharge is present even at rest and can be inhibited by CSNS, and furthermore suggests that CSNS attenuated the pressure‐dependent renin release.

Heart rate turbulence predicts all-cause mortality and sudden death in congestive heart failure patients

Article

Aug 2008

Abnormal heart rate turbulence (HRT) has been documented as a strong predictor of total mortality and sudden death in postinfarction patients, but data in patients with congestive heart failure (CHF) are limited. The aim of this study was to evaluate the prognostic significance of HRT for predicting mortality in CHF patients in New York Heart Association (NYHA) class II-III. In 651 CHF patients with sinus rhythm enrolled into the MUSIC (Muerte Subita en Insuficiencia Cardiaca) study, the standard HRT parameters turbulence onset (TO) and slope (TS), as well as HRT categories, were assessed for predicting total mortality and sudden death. HRT was analyzable in 607 patients, mean age 63 years (434 male), 50% of ischemic etiology. During a median follow up of 44 months, 129 patients died, 52 from sudden death. Abnormal TS and HRT category 2 (HRT2) were independently associated with increased all-cause mortality (HR: 2.10, CI: 1.41 to 3.12, P <.001 and HR: 2.52, CI: 1.56 to 4.05, P <.001; respectively), sudden death (HR: 2.25, CI: 1.13 to 4.46, P = .021 for HRT2), and death due to heart failure progression (HR: 4.11, CI: 1.84 to 9.19, P <.001 for HRT2) after adjustment for clinical covariates in multivariate analysis. The prognostic value of TS for predicting total mortality was similar in various groups dichotomized by age, gender, NYHA class, left ventricular ejection fraction, and CHF etiology. TS was found to be predictive for total mortality only in patients with QRS > 120 ms. HRT is a potent risk predictor for both heart failure and arrhythmic death in patients with class II and III CHF.

Electrical stimulation of the carotid sinus nerve as an experimental treatment of hypertension

Article

Jun 1969

Surgical treatment of hypertension with reference to baropacing

Article

Jun 1966
AM J CARDIOL

Hypertension is a serious cardiovascular disorder. The most common forms of hypertension are those due to increased total peripheral resistance. Currently, two mechanisms are held responsible for increased total peripheral resistance; (1) salt and water retention and (2) neurogenic vasoconstriction. The latter constitutes a significant component of hypertension as may be judged by the effectiveness of sympatholytic drugs, ganglion-blocking agents and sympathectomy in reducing the vasoconstriction on a neurogenic basis. Baropacing attempts to achieve this result through restoring the baroreceptor function in hypertensive states towards normal, thus lowering the blood pressure. Baropacing might be considered a form of “total body physiologic sympathectomy.” The account of baropacing in the first two clinical cases is presented.

Chronic carotid sinus nerve stimulation in the treatment of essential hypertension

Article

Aug 1967
AM J SURG

Electrical stimulation of the carotid nerve has effected reversal of systemic arterial hypertension. The physiologic basis for this new therapeutic approach and the laboratory experiences with acute and prolonged stimulation are reviewed. The engineering specifications of electrical devices employed to date are outlined, and the clinical experience with eleven patients treated with chronic stimulation of the carotid sinus nerves is presented.

Chronic angiotensin II infusion decreases renal norepinephrine overflow in conscious dogs

Article

Sep 1984

Sympathetic nerve activity and in particular renal sympathetic nerve activity were monitored in six conscious dogs subjected to 6 days of intravenous angiotensin (ANG II) infusion (20 ng/kg/min). This was accomplished by measurement of both arterial and renal venous plasma catecholamine concentration. During the initial 4 hours of ANG II infusion, mean arterial pressure (MAP) increased 35 +/- 8 mm Hg from a control value of 101 +/- 4 mm Hg. Although there were no significant changes in arterial plasma norepinephrine (NE) concentration at this time (control = 148 +/- 40 pg/ml), arterial plasma epinephrine (E) concentration increased threefold (control 42 +/- 15 pg/ml). After 24 hours of ANG II infusion, MAP remained elevated (132 +/- 5 mm Hg), but plasma E concentration returned to control levels. From Days 2 through 6 of ANG II infusion, MAP was elevated approximately 40 mm Hg, but there were no chronic increases in either arterial plasma E or NE concentrations. In contrast to arterial plasma catecholamine concentration, renal vein plasma NE concentration (control = 216 +/- 27 pg/ml) actually decreased during both the acute (122 +/- 12 pg/ml) and chronic (103 +/- 26 pg/ml) phases of ANG II infusion. Moreover, renal NE overflow (renal venous plasma NE concentration-arterial plasma NE concentration X effective renal plasma flow), an index of renal sympathetic nerve activity, was depressed during the chronic phase of ANG II hypertension. These results, therefore, do not support the contention that the sympathetic nervous system mediates the hypertension produced by elevated plasma levels of ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

The Relationship of Postoperative Hypertension to Complications following Carotid Endarterectomy

Article

Oct 1980
SURGERY

Severe postoperative hypertension following carotid endarterectomy is a serious and poorly understood clinical problem associated with an increased mortality rate and increased incidence of neurologic deficit. This complication, which is defined as a sustained elevation of systolic pressure greater than 200 mm Hg requiring pharmacologic control, occurred following 19% of 253 carotid procedures. Preoperative hypertension is the single most important determinate in the development of postoperative hypertension. The incidence of preoperative hypertension in patients who developed postoperative hypertension was 79.6% to 57.4% in patients who did not develop this complication (P < 0.01). There was a significantly increased incidence of neurologic deficit and operative mortality rate in the group who developed postoperative hypertension. There were five neurologic deficits in the group who developed postoperative hypertension, for an incidence of 10.2%. The incidence of neurologic deficit in the group who did not develop postoperative hypertension was 3.4%. The only deaths were in the postoperative hypertensive group. The hypertensive patient is at greater risk for postoperative hypertension, which is associated with increased neurologic morbidity and mortality.

Blood pressure responses after carotid surgery: Relationship to postoperative baroreceptor sensitivity

Article

May 1993
AM J MED

Among hypertensive patients after carotid surgery, a group of patients with increased baroreflex sensitivity was identified. In the other group of hypertensive patients, blood pressure and reflex sensitivity were unchanged postoperatively. We hypothesized that a partial readjustment of baroreceptor sensitivity would produce more stable blood pressure profiles. In order to test this hypothesis, a prospective, long-term follow-up study was designed. Blood pressure was monitored in 18 hypertensive and 6 normotensive patients during 6 months using a self-measurement technique. In addition, continuous 24-hour blood pressure monitoring was performed 6 months after surgery. The mean values and the ranges (amplitudes) of systolic and diastolic blood pressure were calculated as indicators for the stability of the circulatory system. Hypertensive patients with unchanged postoperative baroreceptor sensitivity showed significantly more pronounced instabilities of their blood pressure profiles (amplitudes of systolic and diastolic blood pressure p < 0.05 to p < 0.001). A relationship between baroreceptor function and antihypertensive therapy could also be demonstrated, with adequate therapy being much more difficult in patients with reduced or unchanged baroreceptor sensitivity. In contrast to vascular surgery on the aorta or in the region of the lower limbs, carotid surgery is frequently associated with blood pressure changes, demonstrating the essential role of the baroreceptors in the carotid sinus for the regulation of postoperative blood pressure. Since it seems to be the variability of blood pressure, and not the blood pressure level alone, that is critical, close blood pressure monitoring--allowing for an assessment of blood pressure variability--appears to be of particular importance in such patients.

Renal Nerves Promote Sodium Excretion in Angiotensin-Induced Hypertension

Article

Feb 1998

To determine whether the sympathetic nervous system contributes to the hypertension induced by pathophysiological increments in plasma angiotensin II (Ang II) concentration, we determined the neurally induced changes in renal excretory function during chronic intravenous infusion of Ang II. Studies were carried out in five conscious chronically instrumented dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-hour urine collection from the denervated and innervated kidneys. After control measurements, Ang II was infused for 5 days at a rate of 4.8 pmol/kg per minute (5 ng/kg per minute); this was followed by a 5-day recovery period. Twenty-four-hour control values for mean arterial pressure (MAP) and for the ratio of denervated to innervated kidneys (DEN/INN) for urinary sodium, potassium, and creatinine excretion were 93±5 mm Hg, 1.17±0.09, 1.10±0.10, and 1.00±0.02, respectively. As expected, Ang II infusion caused sodium retention for several days before sodium balance was achieved at an elevated MAP (day 5=124±4 mm Hg). Moreover, by day 2 of Ang II-induced hypertension, there were significant reductions in the DEN/INN for sodium and potassium, which persisted for the 5 days of Ang II infusion; on day 5, the DEN/INN values for sodium and potassium were 0.71±0.10 and 0.91±0.12, respectively. In contrast, the DEN/INN for creatinine was unchanged from control levels during Ang II infusion, and measurements of renal hemodynamics indicated comparable reductions in glomerular filtration rate (≈13%) and renal plasma flow (≈25%) during Ang II infusion. This indicates that the renal nerves promoted sodium and potassium excretion during Ang II-induced hypertension by inhibiting tubular reabsorption of these electrolytes. Thus, this study provides no support for the hypothesis that increased renal sympathetic nerve activity impairs sodium excretion and contributes to Ang II-induced hypertension.

Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction

Article

Apr 1999

Identification of high-risk patients after acute myocardial infarction is essential for successful prophylactic therapy. The predictive accuracy of currently used risk predictors is modest even when several factors are combined. Thus, establishment of a new powerful method for risk prediction independent of the available stratifiers is of considerable practical value. The study investigated fluctuations of sinus-rhythm cycle length after a single ventricular premature beat recorded in Holter electrocardiograms, and characterised the fluctuations (termed heart-rate turbulence) by two numerical parameters, termed turbulence onset and slope. The method was developed on a population of 100 patients with coronary heart disease and blindly applied to the population of the Multicentre Post-Infarction Program (MPIP; 577 survivors of acute infarction, 75 deaths during a median follow-up of 22 months) and to the placebo population of the European Myocardial Amiodarone Trial (EMIAT; 614 survivors of acute myocardial infarction, 87 deaths during median follow-up of 21 months). Multivariate risk stratification was done with the new parameters and conventional risk factors. One of the new parameters (turbulence slope) was the most powerful stratifier of follow-up mortality in EMIAT and the second most powerful stratifier in MPIP: MPIP risk ratio 3.5 (95% CI 2.2-5.5, p<0.0001), EMIAT risk ratio 2.7 (1.8-4.2, p<0.0001). In the multivariate analysis, low left-ventricular ejection fraction and turbulence slope were the only independent variables for mortality prediction in MPIP (p<0.001), whereas in EMIAT, five variables were independent mortality predictors: abnormal turbulence onset, abnormal turbulence slope, history of previous infarction, low left-ventricular ejection fraction, and high mean heart rate (p<0.001). In both MPIP and EMIAT, the combination of abnormal onset and slope was the most powerful multivariate risk stratifier: MPIP risk ratio 3.2 (1.7-6.0, p<0.0001), EMIAT risk ratio 3.2 (1.8-5.6, p<0.0001). The absence of the heart rate turbulence after ventricular premature beats is a very potent postinfarction risk stratifier that is independent of other known risk factors and which is stronger than other presently available risk predictors.

Baroreflexes prevent neurally induced sodium retention in angiotensin hypertension

Article

Nov 2000

Recent studies indicate that renal sympathetic nerve activity is chronically suppressed during ANG II hypertension. To determine whether cardiopulmonary reflexes and/or arterial baroreflexes mediate this chronic renal sympathoinhibition, experiments were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. Dogs were studied 1) intact, 2) after thoracic vagal stripping to eliminate afferents from cardiopulmonary and aortic receptors [cardiopulmonary denervation (CPD)], and 3) after subsequent denervation of the carotid sinuses to achieve CPD plus complete sinoaortic denervation (CPD + SAD). After control measurements, ANG II was infused for 5 days at a rate of 5 ng. kg(-1). min(-1). In the intact state, 24-h control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 98 +/- 4 mmHg and 1.04 +/- 0.04, respectively. ANG II caused sodium retention and a sustained increase in MAP of 30-35 mmHg. Throughout ANG II infusion, there was a greater rate of sodium excretion from Inn vs. Den kidneys (day 5 Den/Inn sodium = 0.51 +/- 0.05), indicating chronic suppression of renal sympathetic nerve activity. CPD and CPD + SAD had little or no influence on baseline values for either MAP or the Den/Inn sodium, nor did they alter the severity of ANG II hypertension. However, CPD totally abolished the fall in the Den/Inn sodium in response to ANG II. Furthermore, after CPD + SAD, there was a lower, rather than a higher, rate of sodium excretion from Inn vs. Den kidneys during ANG II infusion (day 5 Den/Inn sodium = 2.02 +/- 0.14). These data suggest that cardiac and/or arterial baroreflexes chronically inhibit renal sympathetic nerve activity during ANG II hypertension and that in the absence of these reflexes, ANG II has sustained renal sympathoexcitatory effects.

Sustained influence of the renal nerves to attenuate sodium retention in angiotensin hypertension

Article

Sep 2001

Recent studies indicate that baroreflex suppression of renal sympathetic nerve activity is sustained for up to 5 days of ANG II infusion; however, steady-state conditions are not associated with ANG II hypertension of this short duration. Thus the major goal of this study was to determine whether neurally induced increments in renal excretory function during chronic intravenous infusion of ANG II are sustained under more chronic conditions when hypertension is stable and sodium balance is achieved. Experiments were conducted in five conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. ANG II was infused after control measurements for 10 days at a rate of 5 ng. kg(-1). min(-1). Twenty-four-hour control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 92 +/- 4 mmHg and 0.99 +/- 0.05, respectively. On days 8-10 of ANG II infusion, MAP was stable (+30 +/- 3 mmHg) and sodium balance was achieved. Whereas equal amounts of sodium were excreted from the kidneys during the control period, throughout ANG II infusion there was a greater rate of sodium excretion from Inn vs. Den kidneys (day 10 Den/Inn sodium = 0.56 +/- 0.05), indicating chronic suppression of renal sympathetic nerve activity. The greater rate of sodium excretion in Inn vs. Den kidneys during renal sympathoinhibition also revealed a latent impairment in sodium excretion from Den kidneys. Although the Den/Inn for sodium and the major metabolites of nitric oxide (NO) decreased in parallel during ANG II hypertension, the Den/Inn for cGMP, a second messenger of NO, remained at control levels throughout this study. This disparity fails to support the notion that a deficiency in NO production and action in Den kidneys accounts for the impaired sodium excretion. Most importantly, these results support the contention that baroreflex suppression of renal sympathetic nerve activity is sustained during chronic ANG II hypertension, a response that may play an important role in attenuating the rise in arterial pressure.

Sustained Activation of the Central Baroreceptor Pathway in Angiotensin Hypertension

Article

Mar 2002
Hypertension

Recent studies indicate that renal sympathetic nerve activity is chronically suppressed in angiotensin (Ang II) hypertension and that baroreflexes play a critical role in mediating this response. To support these findings, we determined whether the hypertension associated with chronic infusion of Ang II at 4.8 pmol/kg per minute (5ng/kg per minute) produces sustained activation of medullary neurons that participate in the central baroreceptor reflex pathway. We used Fos-like (Fos-Li) protein immunohistochemical methods to determine activation of neurons in the nucleus tractus solitarius (NTS), caudal ventrolateral medulla (CVLM), and rostral ventrolateral medulla (RVLM). Results were compared in three groups of chronically instrumented dogs subjected to infusion of: 1) saline (control); 2) Ang II-2 hours (acute); and 3) Ang II-5 days (chronic). Mean arterial pressure increased 22 +/- 3 and 35 +/- 3 mm Hg during acute and chronic Ang II infusion, respectively. There was little Fos-Li immunoreactivity in medullary neurons in control dogs. In contrast, during acute Ang II infusion there was a 2- to 3-fold increase in Fos-Li staining in the NTS and CVLM, but no increase in staining in RVLM neurons. As baroreceptor suppression of sympathoexcitatory cells in the RVLM is mediated by activation of neurons in the NTS and CVLM, these results were expected. More importantly, this same pattern of central neuronal activation was observed during chronic Ang II hypertension. Therefore, these results support recent findings indicating that baroreflex suppression of renal sympathetic nerve activity is a long-term compensatory response in Ang II hypertension.

What Sets the Long-Term Level of Renal Sympathetic Nerve Activity A Role for Angiotensin II and Baroreflexes?

Article

Jul 2003
CIRC RES

Increasing evidence suggests elevated sympathetic outflow may be important in the genesis of hypertension. It is thought that peripheral angiotensin II, in addition to its pressor actions, may act centrally to increase sympathetic nerve activity (SNA). Without direct long-term recordings of SNA, testing the involvement of neural mechanisms in angiotensin II-induced increases in arterial pressure is difficult. Using a novel telemetry-based implantable amplifier, we made continuous recordings of renal SNA (RSNA) before, during, and after 1 week of angiotensin II-based hypertension in rabbits living in their home cages. Angiotensin II infusion (50 ng x kg(-1) x min(-1)) caused a sustained increase in arterial pressure (18+/-3 mm Hg). There was a sustained decrease in RSNA from 18+/-2 normalized units (n.u.) before angiotensin II to 8+/-2 n.u. on day 2 and 9+/-2 n.u. on day 7 of the angiotensin II infusion (P<0.01) before recovering to 17+/-2 n.u. after ceasing angiotensin II. Analysis of the baroreflex response showed that although angiotensin II-induced hypertension led to resetting of the relationship between mean arterial pressure (MAP) and heart rate, there was no evidence of resetting of the MAP-RSNA relationship. We propose that the lack of resetting of the MAP-RSNA curve, with the resting point lying near the lower plateau, suggests the sustained decrease in RSNA during angiotensin II is baroreflex mediated. These results suggest that baroreflex control of RSNA and thus renal function is likely to play a significant role in the control of arterial pressure not only in the short term but also in the long term.

Risk Stratification After Acute Myocardial Infarction by Heart Rate Turbulence

Article

Sep 2003
CIRCULATION

Retrospective postinfarction studies revealed that decreased heart rate turbulence (HRT) indicates increased risk for subsequent death. This is the first prospective study to validate HRT in a large cohort of the reperfusion era. One thousand four hundred fifty-five survivors of an acute myocardial infarction (age <76 years) in sinus rhythm were enrolled. HRT onset (TO) and slope (TS) were calculated from Holter records. Patients were classified into the following HRT categories: category 0 if both TO and TS were normal, category 1 if either TO or TS was abnormal, or category 2 if both TO and TS were abnormal. The primary end point was all-cause mortality. During a follow-up of 22 months, 70 patients died. Multivariately, HRT category 2 was the strongest predictor of death (hazard ratio, 5.9; 95% CI, 2.9 to 12.2), followed by left ventricular ejection fraction (LVEF) < or =30% (4.5; 2.6 to 7.8), diabetes mellitus (2.5; 1.6 to 4.1), age > or =65 years (2.4; 1.5 to 3.9), and HRT category 1 (2.4; 1.2 to 4.9). LVEF < or =30% had a sensitivity of 27% at a positive predictive accuracy level of 23%. The combined criteria of LVEF < or =30%, HRT category 2 or LVEF >30%, age > or =65 years, diabetes mellitus, and HRT category 2 had a sensitivity of 24% at a positive predictive accuracy level of 37%. The combined criteria of LVEF < or =30% or LVEF >30%, age > or =65 years, diabetes mellitus, and HRT category 1 or 2 had a sensitivity of 44% at a positive predictive accuracy level of 23%. HRT is a strong predictor of subsequent death in postinfarction patients of the reperfusion era.

Prolonged Activation of the Baroreflex Produces Sustained Hypotension

Article

Mar 2004
Hypertension

The role of baroreflexes in long-term control of arterial pressure is unresolved. To determine whether chronic activation of the baroreflex produces sustained hypotension, we developed a method for prolonged activation of the carotid baroreflex in conscious dogs. This was achieved by chronically implanting electrodes around both carotid sinuses and using an externally adjustable pulse generator to electrically activate the carotid baroreflex. Control values for mean arterial pressure (MAP) and heart rate were 93+/-3 mm Hg and 64+/-4 bpm, respectively. After control measurements, the carotid baroreflex was activated bilaterally for 7 days at a level that produced a prompt and substantial reduction in MAP, and for day 1 MAP was reduced to 75+/-4 mm Hg. Moreover, this hypotensive response was sustained throughout the entire 7 days of baroreflex activation (day 7, MAP=72+/-5 mm Hg). During prolonged baroreflex activation, heart rate decreased in parallel with MAP, although the changes were not as pronounced (day 7, heart rate=51+/-3 bpm). Prolonged baroreflex activation was also associated with approximately 35% reduction in plasma norepinephrine concentration (control=87+/-15 pg/mL). After baroreflex activation, hemodynamic measures and plasma levels of norepinephrine returned to control levels. Interestingly, despite the pronounced fall in MAP, plasma renin activity did not increase during prolonged baroreflex activation. These data indicate that prolonged baroreflex activation can lead to substantial reductions in MAP by suppressing the sympathetic nervous system. Furthermore, sustained sympathoinhibitory effects on renin secretion may play an important role in mediating the long-term hypotensive response.

Software for advanced HRV Analysis

Article

Nov 2004
COMPUT METH PROG BIO

A computer program for advanced heart rate variability (HRV) analysis is presented. The program calculates all the commonly used time- and frequency-domain measures of HRV as well as the nonlinear Poincaré plot. In frequency-domain analysis parametric and nonparametric spectrum estimates are calculated. The program generates an informative printable report sheet which can be exported to various file formats including the portable document format (PDF). Results can also be saved as an ASCII file from which they can be imported to a spreadsheet program such as the Microsoft Excel. Together with a modern heart rate monitor capable of recording RR intervals this freely distributed program forms a complete low-cost HRV measuring and analysis system.

Baroreceptors, baroreceptor unloading, and the long-term control of blood pressure

Article

May 2005

T N Thrasher

Whether arterial baroreceptors play a role in setting the long-term level of mean arterial pressure (MAP) has been debated for more than 75 years. Because baroreceptor input is reciprocally related to efferent sympathetic nerve activity (SNA), it is obvious that baroreceptor unloading would cause an increase in MAP. Experimental proof of concept is evident acutely after baroreceptor denervation. Chronically, however, baroreceptor denervation is associated with highly variable changes in MAP but not sustained hypertension. The ability of baroreceptors to buffer imposed increases in MAP appears limited by a process termed "resetting," in which the threshold to fire shifts in the direction of the pressure change and if the pressure elevation is maintained, it leads to a rightward shift in the relationship between baroreceptor firing and MAP. The most common hypothesis linking baroreceptors to changes in MAP proposes that reduced vascular distensibility in baroreceptive areas would cause reduced firing at the same pulsatile pressure and, thus, reflexively increase SNA. This review focuses on effects of baroreceptor denervation in the regulation of MAP in human subjects compared with animal studies; the relationship between vascular compliance, MAP, and baroreceptor resetting; and, finally, the effect of chronic baroreceptor unloading on the regulation of MAP.

Baroreceptor Denervation Prevents Sympathoinhibition During Angiotensin II–Induced Hypertension

Article

Aug 2005
Hypertension

Arterial baroreflexes are well established to provide the basis for short-term control of arterial pressure; however, their role in long-term pressure control is more controversial. We proposed that if the sustained decrease in renal sympathetic nerve activity (RSNA) we observed previously in response to angiotensin II-induced hypertension is baroreflex mediated, then the decrease in RSNA in response to angiotensin II would not occur in sinoaortic-denervated (SAD) animals. Arterial pressure and RSNA were recorded continuously via telemetry in sham and SAD rabbits living in their home cages before, during, and after a 7-day infusion of angiotensin II (50 ng . kg(-1) . min(-1)). The arterial pressure responses in the 2 groups of rabbits were not significantly different (82+/-3 mm Hg sham versus 83+/-3 mm Hg SAD before angiotensin II infusion, and 101+/-6 mm Hg sham versus 100+/-4 mm Hg SAD day 6 of angiotensin II). In sham rabbits, there was a significant sustained decrease in RSNA (53+/-7% of baseline on day 2 and 65+/-7% on day 6 of the angiotensin II). On ceasing the angiotensin II, all variables recovered to baseline. In contrast, RSNA did not change in SAD rabbits with the angiotensin II infusion (RSNA was 98+/-8% of baseline on day 2 and 98+/-8% on day 6 of the angiotensin II infusion). These results support our hypothesis that the reduction in RSNA in response to a pressor dose of angiotensin II is dependent on an intact arterial baroreflex pathway.

Carotid artery stenting and endarterectomy have different effect on heart rate variability

Article

Mar 2006
J NEUROL SCI

Due to their close proximity to the carotid sinus baroreceptor region, carotid endarterectomy (CEA) and carotid angioplasty/stenting (CAS) carry an inherent risk of affecting baroreflex-mediated regulation of the heart rate. Variations in the heart rate can be studied by measuring heart rate variability (HRV), in which distinct frequency bands in the power spectrum represent sympathetic and parasympathetic modulations on sinus node pacemaker activity. We aimed to investigate the influence of CEA and CAS on HRV. One-hour recordings of R-R intervals on ECG were obtained before and after CEA (10 patients) or CAS (12 patients). The power spectrum of the R-R time series was estimated using the FFT technique. The power in low frequency (LF) and high frequency (HF) bands were computed and normalized to their total power (TP). The LF/HF ratio, an index of sympathovagal balance, was calculated. Compared to preoperative levels, LF/HF exhibited 85%, 96%, and 70% increase on the second, third, and fourth days after CEA, respectively. In contrast, LF/HF decreased by 26%, 32%, and 26% on the respective days following CAS; the difference between groups was significant (p=0.0069). Normalized LF increased after CEA and decreased after CAS, while the opposite was observed for normalized HF (p=0.0217). There was no significant change in TP. CEA and CAS have differential effects on the sympathovagal balance on the heart. The relative increase in sympathetic modulation after CEA and parasympathetic modulation after CAS are likely mediated by alterations in the sensitivity of carotid sinus baroreceptors. Altered cardiac autonomic modulation may play a role in the occurrence of cardiac disturbances following carotid interventions.

Increased Sympathetic Nerve Activity Correlates With Neurovascular Compression at the Rostral Ventrolateral Medulla

Article

Jun 2006
Hypertension

We used microneurography to measure muscle sympathetic nerve activity (MSNA) in 25 hypertensive subjects and correlated these results with the presence or absence of signs of neurovascular compression (NVC) at the rostral ventrolateral (RVL) medulla on MRI. Subjects were divided into 3 groups based on MRI findings: NVC-, no MRI evidence of NVC (N=9); NVC+contact, image showing artery in contact but not compressing the RVL medulla (N=8); and NVC+compression, image showing arterial compression of the RVL medulla (N=8). The MSNA measurements were performed at rest, after a hypothermic stimulus, and during isometric exercise. The MSNA during rest in the NVC+compression group was significantly higher than that in the NVC+contact and NVC- groups (30.4+/-3.4 versus 17.5+/-1.1 and 21.4+/-3.2 spikes per minute, respectively). However, the blood pressure in the NVC+compression group was slightly but not significantly higher than that in the other 2 groups (183+/-7/115+/-8, 174+/-6/108+/-7, and 171+/-5/110+/-5 mm Hg, respectively). The increases in MSNA, blood pressure, and heart rate during the cold pressor and isometric exercise tests were similar. Our results show that, although resting MSNA is elevated in patients with true NVC of the RVL medulla, patients without NVC or with arterial contact but not overt compression of the RVL medulla have similar MSNA. These findings are important for identifying, among hypertensive patients with NVC, individuals who may have associated physiological repercussions, such as increased sympathetic activity.

Noninvasive investigation of autonomic activity after carotid stenting or carotid endarterectomy

Article

Sep 2006
J VASC SURG

Objective: Carotid artery stenting (CAS) has been introduced as an alternative to carotid endarterectomy (CEA) for the treatment of carotid artery stenosis. Both techniques seem to be associated with postoperative hemodynamic lability. Both may induce baroreceptor dysfunction, possibly leading to transient impairment of cardiovascular autonomic activity and resulting in hemodynamic instability. This instability might contribute to postoperative morbidity. To elucidate these phenomena, we studied the cardiac baroreflex and autonomic cardiovascular control after CAS and CEA. Method: In 20 patients scheduled for CAS (n = 10) or CEA (n = 10), intra-arterial pressures and electrocardiograms were recorded during 10 minutes before and 8 and 24 hours after the procedure. Spontaneous cardiac baroreflex sensitivity was assessed using the sequence method and cross-spectral analysis. In addition, cardiovascular autonomic activity was investigated using spectral analysis of heart rate variability and systolic arterial pressure variability. Results: After CAS, we demonstrated an increase of the spontaneous baroreflex sensitivity median (interquartile range) from 5.6 (5.1 to 6.2) ms/mm Hg before the procedure to 8.8 (6.8 to 10.5) ms/mm Hg and 7.7 (3.9 to 8.6) ms/mm Hg (P < .001), 8 and 24 hours after the procedure. This was consistent with the increase of the high frequency component of heart rate variability reflecting cardiac parasympathetic activity and a decrease of the low frequency of systolic arterial pressure variability reflecting sympathetic vascular activity. The postoperative period was also associated with decreased systolic arterial pressure from 173 (162 to 190) mm Hg at baseline to 122 (109 to 143) mm Hg and 136 (121 to 143) mm Hg at 8 and 24 hours after CAS (P < .001). No changes in baroreflex sensitivity or in autonomic activity were observed after CEA. Conclusions: These preliminary data suggest that CAS is associated with parasympathetic predominance postoperatively and may probably explain the lower systolic arterial pressure observed after CAS.

An implantable carotid sinus stimulator for drug-resistant hypertension: Surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial

Article

Jan 2007
J VASC SURG

A large number of patients have hypertension that is resistant to currently available pharmacologic therapy. Electrical stimulation of the carotid sinus baroreflex system has been shown to produce significant chronic blood pressure decreases in animals. The phase II Rheos Feasibility Trial was performed to assess the response of patients with multidrug-resistant hypertension to such stimulation. The system consists of an implantable pulse generator with bilateral perivascular carotid sinus leads. Implantation is performed bilaterally with patients under narcotic anesthesia (to preserve the reflex for assessment of optimal lead placement). Dose-response testing at 0 to 6 V is assessed before discharge and at monthly intervals thereafter; the device is activated after 1 month's recovery time. This was a Food and Drug Administration-monitored phase II trial performed at five centers in the United States. Ten patients with resistant hypertension (taking a median of six antihypertensive medications) underwent implantation. All 10 were successful, with no significant morbidity. The mean procedure time was 198 minutes. There were no adverse events attributable to the device. Predischarge dose-response testing revealed consistent (r = .88) reductions in systolic blood pressure of 41 mm Hg (mean fall is from 180-139 mm Hg), with a peak response at 4.8 V (P < .001) and without significant bradycardia or bothersome symptoms. A surgically implantable device for electrical stimulation of the carotid baroreflex system can be placed safely and produces a significant acute decrease in blood pressure without significant side effects.

Prolonged Activation of the Baroreflex Abolishes Obesity-Induced Hypertension

Article

Jul 2007
Hypertension

Prolonged electrical activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure in normotensive dogs. The main goal of this study was to assess the influence of prolonged baroreflex activation on arterial pressure and neurohormonal responses in 6 dogs with obesity-induced hypertension. After control measurements, the diet was supplemented with cooked beef fat for 6 weeks, whereas sodium intake was held constant. After 4 weeks of the high-fat diet, there were increments in body weight from 25.8+/-0.7 to 38.6+/-1.0 kg, mean arterial pressure from 97+/-2 to 110+/-3 mm Hg, heart rate from 67+/-3 to 91+/-4 bpm, and plasma norepinephrine concentration from 141+/-35 to 280+/-52 pg/mL. Plasma glucose and insulin concentrations were elevated, but increases in plasma renin activity during the initial weeks of the high-fat diet were not sustained. During week 5, baroreflex activation resulted in sustained reductions in mean arterial pressure, heart rate, and plasma norepinephrine concentration; at the end of week 5, these values were 87+/-2 mm Hg, 77+/-4 bpm, and 166+/-45 pg/mL, respectively. These suppressed values returned to week 4 levels during a 7-day recovery period after baroreflex activation. There were no changes in plasma glucose or insulin concentrations, or plasma renin activity during prolonged baroreflex activation. These findings indicate that baroreflex activation can chronically suppress the sympathoexcitation associated with obesity and abolish the attendant hypertension while having no effect on hyperinsulinemia or hyperglycemia.

Chronic Baroreceptor Activation Enhances Survival in Dogs With Pacing-Induced Heart Failure

Article

Nov 2007
Hypertension

Much of the current pharmacological therapy for chronic heart failure targets neurohormonal activation. In spite of recent advances in drug therapy, the mortality rate for chronic heart failure remains high. Activation of the carotid baroreceptor (BR) reduces sympathetic outflow and augments vagal tone. We investigated the effect of chronic activation of the carotid BR on hemodynamic and neurohormonal parameters and on mortality in dogs with chronic heart failure. Fifteen dogs were instrumented to record hemodynamics. Electrodes were applied around the carotid sinuses to allow for activation of the BR. After 2 weeks of pacing (250 bpm), electrical carotid BR activation was initiated in 7 dogs and continued for the remainder of the study. The start of BR activation was used as a time reference point for the remaining 8 control dogs that did not receive BR activation. Survival was significantly greater for dogs undergoing carotid BR activation compared with control dogs (68.1+/-7.4 versus 37.3+/-3.2 days, respectively; P<0.01), although arterial pressure, resting heart rate, and left ventricular pressure were not different over time in BR-activated versus control dogs. Plasma norepinephrine was lower in dogs receiving BR activation therapy 31 days after the start of BR activation (401.9+/-151.5 versus 1121.9+/-389.1 pg/mL in dogs not receiving activation therapy; P<0.05). Plasma angiotensin II increased less in dogs receiving activation therapy (plasma angiotensin II increased by 157.4+/-58.6 pg/mL in control dogs versus 10.1+/-14.0 pg/mL in dogs receiving activation therapy; P<0.02). We conclude that chronic activation of the carotid BR improves survival and suppresses neurohormonal activation in chronic heart failure.

Management of Uncontrollable Hypertension With a Carotid Sinus Stimulation Device

Article

Dec 2007
Hypertension

Device Based Therapy in Hypertension Extension Trial (DEBuT-HET) Available at: http://clinicaltrials.gov/ct2

Mar 2009

National Institutes of Health. Device Based Therapy in Hypertension Extension Trial (DEBuT-HET). Available at: http://clinicaltrials.gov/ct2/ show/NCT00710294. Accessed March 15, 2009.

Effects of Chronic Baroreceptor Stimulation on the Autonomic Cardiovascular Regulation in Patients With Drug-Resistant Arterial Hypertension

Abstract

No full-text available

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