Independent Factors Influencing Changes in Baroreceptor Sensitivity after Carotid Endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is a well-established standard therapy for patients with symptomatic or asymptomatic high-grade carotid stenosis. The aim of carotid endarterectomy is to decrease the risk of stroke and avoid relevant functional loss. However, carotid endarterectomy is known to be associated with hemodynamic dysregulation. In this study we compared eversion CEA (E-CEA) and conventional CEA (C-CEA) regarding postoperative blood pressure values as well as preoperative and postoperative baroreceptor sensitivity in the first 7 days after surgery. The aim was to find possible factors influencing changes in baroreceptor sensitivity. METHODS: Patients (111 patients were enrolled, of which 50 patients received C-CEA and 61 patients E-CEA) were prospectively enrolled in this study. For the measurement of baroreceptor sensitivity, a noninvasive Finometer measuring device from Finapres Medical System B.V. (Amsterdam, The Netherlands) was used. Measurements were performed 1 day before surgery (PRE), directly after surgery (F1), on day 1 (F2), day 2 (F3), and on day 7 (F4) postoperatively. RESULTS: Postoperative blood pressure values were significantly higher in the E-CEA group on the day of surgery (F1) (P < 0.001) and on day 1 (F2) (P < 0.001). From day 2 (F3, F4) postoperatively, no significant difference was found between the 2 groups. The invasive blood pressure measurement in the postoperative recovery room showed significantly higher systolic blood pressure values in the E-CEA group (P = 0.001). The need of acute antihypertensive therapy was significantly higher in the recovery room in the E-CEA group (P = 0.020). With regard to changes in baroreceptor sensitivity, significantly lower baroreceptor sensitivity (BRS) values were recorded in the E-CEA group at 1 day (F2) postoperatively (P = 0.005). The regression analysis showed that the applied surgical technique and the patient's age were significant factors influencing changes in baroreceptor sensitivity. CONCLUSIONS: In this study we could confirm higher blood pressure levels after E-CEA in the first 2 days after surgery. Additionally, we identified 22 factors possibly influencing baroreceptor sensitivity: surgical technique and age. Based on the data obtained in this study, hemodynamic dysregulation after CEA (E-CEA, C-CEA) is temporary and short-term. Already after the second postoperative day, there was no significant difference between the E-CEA and E-CEA groups, this effect remained stable after 7 days.

Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis.

[Figure: see text].

The protective role of SOD1 overexpression in central mediation of bradycardia following chronic intermittent hypoxia in mice.

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is associated with many cardiovascular complications. Similar to OSA, chronic intermittent hypoxia (CIH) (a model for OSA) leads to oxidative stress and impairs baroreflex control of the heart rate (HR) in rodents. The baroreflex arc includes the aortic depressor nerve (ADN), vagal efferent, and central neurons. In this study, we used mice as a model to examine the effects of CIH on baroreflex sensitivity, aortic baroreceptor afferents, and central and vagal efferent components of the baroreflex circuitry. Furthermore, we tested whether human Cu/Zn Superoxide Dismutase (SOD1) overexpression in transgenic mice offers protection against CIH-induced deficit of the baroreflex arc. Wild-type C57BL/6J and SOD1 mice were exposed to room air (RA) or CIH and were then anesthetized, ventilated, and catheterized for measurement of mean arterial pressure (MAP) and HR. Compared with wild-type RA control, CIH impaired baroreflex sensitivity but increased maximum baroreceptor gain and bradycardic response to vagal efferent stimulation. Additionally, CIH reduced the bradycardic response to ADN stimulation, indicating a diminished central regulation of bradycardia. Interestingly, SOD1 overexpression prevented CIH-induced attenuation of HR responses to ADN stimulation and preserved HR responses to vagal efferent stimulation in transgenic mice. We suggest that CIH decreased central mediation of the baroreflex and SOD1 overexpression may prevent the CIH-induced central deficit.

Cost-impact analysis of baroreflex activation therapy in chronic heart failure patients in the United States.

BACKGROUND: The study evaluated the cost of baroreflex activation therapy plus guideline directed therapy (BAT + GDT) compared to GDT alone for HF patients with reduced ejection fraction and New York Heart Association Class III or II (with a recent history of III). Baroreflex activation therapy (BAT) is delivered by an implantable device that stimulates the baroreceptors through an electrode attached to the outside of the carotid artery, which rebalances the autonomic nervous system to regain cardiovascular (CV) homeostasis. The BeAT-HF trial evaluated the safety and effectiveness of BAT. METHODS: A cost impact model was developed from a U.S. health care payer or integrated delivery network perspective over a 3-year period for BAT + GDT versus GDT alone. Expected costs were calculated by utilizing 6-month data from the BeAT-HF trial and existing literature. HF hospitalization rates were extrapolated based on improvement in NT-proBNP. RESULTS: At baseline the expected cost of BAT + GDT were $29,526 per patient more than GDT alone due to BAT device and implantation costs. After 3 years, the predicted cost per patient was $9521 less expensive for BAT + GDT versus GDT alone due to lower rates of significant HF hospitalizations, CV non-HF hospitalizations, and resource intensive late-stage procedures (LVADs and heart transplants) among the BAT + GDT group. CONCLUSIONS: BAT + GDT treatment becomes less costly than GDT alone beginning between years 1 and 2 and becomes less costly cumulatively between years 2 and 3, potentially providing significant savings over time. As additional BeAT-HF trial data become available, the model can be updated to show longer term effects.

Effects of carotid baroreceptor stimulation on aortic remodeling in obese rats.

BACKGROUND AND AIM: Our previous study found carotid baroreceptor stimulation (CBS) reduces body weight and white adipose tissue (WAT) weight, restores abnormal secretion of adipocytokines and inflammation factors, decreases systolic blood pressure (SBP) by inhibiting activation of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in obese rats. In this study, we explore effects of CBS on aortic remodeling in obese rats. METHODS AND RESULTS: Rats were fed high-fat diet (HFD) for 16 weeks to induce obesity and underwent either CBS device implantation and stimulation or sham operation at 8 weeks. BP and body weight were measured weekly. RAS activity of WAT, histological, biochemical and functional profiles of aortas were detected after 16 weeks. CBS effectively decreased BP in obese rats, downregulated mRNA expression of angiotensinogen (AGT) and renin in WAT, concentrations of AGT, renin, angiotensin II (Ang II), protein levels of Ang II receptor 1 (AT1R) and Ang II receptor 2 (AT2R) in WAT were declined. CBS inhibited reactive oxygen species (ROS) generation, inflammatory response and endoplasmic reticulum (ER) stress in aortas of obese rats, restrained vascular wall thickening and vascular smooth muscle cells (VSMCs) phenotypic switching, increased nitric oxide (NO) synthesis, promoted endothelium-dependent vasodilatation by decreasing protein expression of AT1R and leptin receptor (LepR), increasing protein expression of adiponectin receptor 1 (AdipoR1) in aortic VSMCs. CONCLUSION: CBS reduced BP and reversed aortic remodeling in obese rats, the underlying mechanism might be related to the suppressed SNS activity, restored adipocytokine secretion and restrained RAS activity of WAT.

Transient Receptor Potential Vanilloid 4 Regulation of Adenosine Triphosphate Release by the Adenosine Triphosphate Transporter Vesicular Nucleotide Transporter, a Novel Therapeutic Target for Gastrointestinal Baroreception and Chronic Inflammation.

BACKGROUND: Transient receptor potential vanilloid 4 (TRPV4) is activated by stretch (mechanical), warm temperature, some epoxyeicosatrienoic acids, and lipopolysaccharide. TRPV4 is expressed throughout the gastrointestinal epithelia and its activation induces adenosine triphosphate (ATP) exocytosis that is involved in visceral hypersensitivity. As an ATP transporter, vesicular nucleotide transporter (VNUT) mediates ATP storage in secretory vesicles and ATP release via exocytosis upon stimulation. SUMMARY: TRPV4 is sensitized under inflammatory conditions by a variety of factors, including proteases and serotonin, whereas methylation-dependent silencing of TRPV4 expression is associated with various pathophysiological conditions. Gastrointestinal epithelia also release ATP in response to hypo-osmolality or acid through molecular mechanisms that remain unclear. These synergistically released ATP could be involved in visceral hypersensitivity. Low concentrations of the first generation bisphosphate, clodronate, were recently reported to inhibit VNUT activity and thus clodronate may be a safe and potent therapeutic option to treat visceral pain. Key Messages: This review focuses on: (1) ATP and TRPV4 activities in gastrointestinal epithelia; (2) factors that could modulate TRPV4 activity in gastrointestinal epithelia; and (3) the inhibition of VNUT as a potential novel therapeutic strategy for functional gastrointestinal disorders.

Hydraulic stimulation of carotid artery baroreceptors as a likely cause of transient asystolic cardiac arrest during diagnostic angiography or surgical endarterectomy.

We describe two patients-both who underwent general anesthesia-in whom we theorize that hydraulic pressure on carotid artery baroreceptors resulted in transient asystolic cardiac arrest (TACA) during diagnostic or therapeutic procedures. Patient #1 was a 58-year-old female who experienced TACA in response to rapid injection of radiocontrast material into the carotid artery during diagnostic cerebral angiography. Her history was remarkable for aneurysmal subarachnoid hemorrhage at least 13 hr prior to angiography, radiographic evidence of intracranial hypertension, and baseline bradycardia, collectively suggestive of increases in baseline vagal tone. Potentially contributing to TACA, the patient had a 90° curve in the internal carotid artery, just distal to the carotid bifurcation and tip of the angiography catheter, that likely diminished runoff of injected contrast solution and, in turn, would have exacerbated any intracarotid pressure increases in response to injection. There was no evidence of increased baseline vagal tone in Patient #2, a 79-year-old female having carotid endarterectomy surgery. She experienced TACA immediately after full release of an occlusive clamp on the common carotid artery proximal to the now closed carotid arteriotomy, but while the internal carotid was still occluded. Of note, the carotid artery baroreceptors were not treated with local anesthetic in these patients, thus they should have retained much of their normal function. We describe the possible pathomechanisms involved in TACA in these patients, measures to diminish the likelihood of the phenomenon occurring in future patients, and methods for treating the asystole.

Pulmonary Artery Denervation: Update on Clinical Studies.

PURPOSE OF REVIEW: Sympathetic overactivity plays an important role in the progression of pulmonary arterial hypertension (PAH). The purpose of this review is to illustrate localization of pulmonary arterial sympathetic nerves, the key steps of pulmonary artery denervation (PADN) procedure, and to highlight clinical outcomes. RECENT FINDINGS: Sympathetic nerves mostly occurred in the posterior region of the bifurcation and pulmonary trunk. Emerging preclinical data provided the potential of PADN for PAH. PADN, produced at bifurcation area, improved a profound reduction of pulmonary arterial pressure and ameliorated clinical outcomes with an exclusive ablation catheter. The application of PADN in the patients of PAH or combined pre-capillary and post-capillary PH (CpcPH) improved the hemodynamic parameters and increased 6MWD. Sympathetic overactivity aggravates PAH. PADN is a promising interventional treatment for PAH and CpcPH. Additional clinical trials are warranted to confirm the efficacy of PADN.

Carotid Endarterectomy with Autoarterial Remodeling of Bifurcation of the Common Carotid Artery and Carotid Endarterectomy with Patch Closure: Comparison of Methods.

BACKGROUND: The objectives of our research were to identify whether the new method of carotid endarterectomy (CEA) with autoarterial remodeling of bifurcation of the common carotid artery (ARBCCA) influences daily parameters of blood pressure and heart rate (HR) while monitoring them on a daily basis and to assess the efficacy of the suggested method. MATERIALS AND METHODS: It is a prospective randomized comparative study. The first group (n = 100) included patients that underwent ARBCCA, the second group (n = 100) included patients that underwent "classic" CEA with xenopericardial patch closure. Diurnal Holter recording of blood pressure and (HR) was performed before and after the surgical treatment in both groups. RESULTS: Surgical treatment in both groups leads to an increase of HR, arterial hypertension time index by systolic blood pressure, and arterial hypertension time index by diastolic arterial blood pressure. The damage of carotid artery bulb increases sympathetic innervation and causes dysregulation of the baroreceptor mechanism. CONCLUSIONS: In our study, we did not reveal a significant difference in the incidence of postoperative hypertension and the dependence of HR on the choice of surgical technique. Thus, the proposed ARBCCA method does not lead to an increased risk of pre-existing arterial hypertension development. A significant difference is found out on the parameter of the clamping time of carotid arteries in favor to ARBCCA group. Another advantage of the suggested technique is the number of restenosis greater than 50% during the 2-year follow-up (4 [4%] cases (ARBCCA group) versus 12 [12%] cases ["classic" CEA], respectively, P = .037).

Role of the heart in blood pressure lowering during chronic baroreflex activation: insight from an in silico analysis.

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 (RSNA) and cardiac autonomic activity cannot be achieved experimentally, we used an established mathematical model of human physiology (HumMod) to provide mechanistic insights 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 (ANP), providing validation of the model. Simulations showed that baroreflex-induced alterations in cardiac sympathetic and parasympathetic activity lead to a sustained depression of cardiac function and increased secretion of ANP. Increased ANP and suppression of RSNA both enhanced renal excretory function and accounted for most of the chronic blood pressure lowering during baroreflex activation. However, when suppression of RSNA 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 ANP 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. NEW & NOTEWORTHY Both experimental and clinical studies have shown that the presence of renal nerves is not an obligate requirement for sustained reductions in blood pressure during chronic electrical stimulation of the carotid baroreflex. Simulations using HumMod, a mathematical model of integrative human physiology, indicated that both increased secretion of atrial natriuretic peptide and suppressed renal sympathetic nerve activity play key roles in mediating long-term reductions in blood pressure during chronic baroreflex activation.

Altered arterial baroreflex-muscle metaboreflex interaction in heart failure.

Two powerful reflexes controlling cardiovascular function during exercise are the muscle metaboreflex and arterial baroreflex. In heart failure (HF), the strength and mechanisms of these reflexes are altered. Muscle metaboreflex activation (MMA) in normal subjects increases mean arterial pressure (MAP) primarily via increases in cardiac output (CO), whereas in HF the mechanism shifts to peripheral vasoconstriction. Baroreceptor unloading increases MAP via peripheral vasoconstriction, and this pressor response is blunted in HF. Baroreceptor unloading during MMA in normal animals elicits an enormous pressor response via combined increases in CO and peripheral vasoconstriction. The mode of interaction between these reflexes is intimately dependent on the parameter (e.g., MAP and CO) being investigated. The interaction between the two reflexes when activated simultaneously during dynamic exercise in HF is unknown. We activated the muscle metaboreflex in chronically instrumented dogs during mild exercise (via graded reductions in hindlimb blood flow) followed by baroreceptor unloading [via bilateral carotid occlusion (BCO)] before and after induction of HF. We hypothesized that BCO during MMA in HF would cause a smaller increase in MAP and a larger vasoconstriction of ischemic hindlimb vasculature, which would attenuate the restoration of blood flow to ischemic muscle observed in normal dogs. We observed that BCO during MMA in HF increases MAP by substantial vasoconstriction of all vascular beds, including ischemic active muscle, and that all cardiovascular responses, except ventricular function, exhibit occlusive interaction. We conclude that vasoconstriction of ischemic active skeletal muscle in response to baroreceptor unloading during MMA attenuates restoration of hindlimb blood flow. NEW & NOTEWORTHY We found that baroreceptor unloading during the muscle metaboreflex in heart failure results in occlusive interaction (except for ventricular function) with significant vasoconstriction of all vascular beds. In addition, restoration of blood flow to ischemic active muscle, via preferentially larger vasoconstriction of nonischemic beds, is significantly attenuated in heart failure.

Cardiac vanilloid receptor-1 afferent depletion enhances stellate ganglion neuronal activity and efferent sympathetic response to cardiac stress.

Afferent fibers expressing the vanilloid receptor 1 (VR1) channel have been implicated in cardiac nociception; however, their role in modulating reflex responses to cardiac stress is not well understood. We evaluated this role in Yorkshire pigs by percutaneous epicardial application of resiniferatoxin (RTX), a toxic activator of the VR1 channel, resulting in the depletion of cardiac VR1-expressing afferents. Hemodynamics, epicardial activation recovery intervals, and in vivo activity of stellate ganglion neurons (SGNs) were recorded in control and RTX-treated animals. Stressors included inferior vena cava or aortic occlusion and rapid right ventricular pacing (RVP) to induce dyssynchrony and ischemia. In the epicardium, stellate ganglia, and dorsal root ganglia, immunostaining for the VR1 channel, calcitonin gene-related peptide, and substance P was significantly diminished by RTX. RTX-treated animals exhibited higher basal systolic blood pressures and contractility than control animals. Reflex responses to epicardial bradykinin and capsaicin were mitigated by RTX. Cardiovascular reflex function, as assessed by inferior vena cava or aortic occlusion, was similar in RTX-treated versus control animals. RTX-treated animals exhibited resistance to hemodynamic collapse induced by RVP. Activation recovery interval shortening during RVP, a marker of cardiac sympathetic outflow, was greater in RTX-treated animals and exhibited significant delay in returning to baseline values after cessation of RVP. The basal firing rate of SGNs and firing rates in response to RVP were also greater in RTX-treated animals, as was the SGN network activity in response to cardiac stressors. These data suggest that elimination of cardiac nociceptive afferents reorganizes the central-peripheral nervous system interaction to enhance cardiac sympathetic outflow. NEW & NOTEWORTHY Our work demonstrates a role for cardiac vanilloid receptor-1-expressing afferents in reflex processing of cardiovascular stress. Current understanding suggests that elimination of vanilloid receptor-1 afferents would decrease reflex cardiac sympathetic outflow. We found, paradoxically, that sympathetic outflow to the heart is instead enhanced at baseline and during cardiac stress.

Sympathetically mediated cardiac responses to isolated muscle metaboreflex activation following exercise are modulated by body position in humans.

Isolated muscle metaboreflex activation with posthandgrip exercise ischemia (PEI) increases sympathetic nerve activity and partially maintains the exercise-induced increase in blood pressure, but a smaller heart rate (HR) response occurs. The cardiopulmonary baroreceptors, mechanically sensitive receptors that respond to changes in central blood volume and pressure, are strongly associated with changes in body position and upon activation elicit reflex sympathoinhibition. Here, we tested the hypothesis that postural changes modulate the sympathetically mediated cardiac response to PEI in humans. Beat-to-beat HR (electrocardiography) and blood pressure (finger photoplethysmography) were continuously measured, and cardiac function was assessed by echocardiography in 13 healthy men (21 ± 3 yr). After a 15-min rest period, 90-s static handgrip at 40% maximum voluntary contraction was performed followed by 3 min of PEI. Four trials were randomly conducted during either seated or supine position with and without ß1-adrenergic blockade (25 mg atenolol). During PEI under control conditions, HR remained elevated from baseline in the seated [change (Δ): 4 ± 1 beats/min] but not in the supine (change: -1 ± 1 beats/min) position. Similarly, stroke volume and cardiac output were increased from baseline in the seated (∆13.0 ± 2.4 ml and ∆1.1 ± 0.2 l/min, respectively) but not in the supine (∆2.5 ± 2.9 ml and ∆0.13 ± 0.20 l/min, respectively) position. During ß1-adrenergic blockade, HR, stroke volume, and cardiac output remained unchanged in both conditions. We conclude that sympathetically mediated cardiac responses to PEI are influenced by changes in body position. These findings indicated that muscle metaboreflex and cardiopulmonary baroreflex have an interactive influence on the neural control of cardiovascular function in humans. NEW & NOTEWORTHY In the present study, we demonstrated that muscle metaboreflex activation increases heart rate, stroke volume, and cardiac output in the seated position but not in the supine position and not after ß1-adrenergic blockade. These findings indicate that sympathetically mediated cardiac responses to isolated muscle metaboreflex activation after exercise are modulated by central blood volume mobilization.

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

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.

Anaphylactic hypotension causes renal and adrenal sympathoexcitaion and induces c-fos in the hypothalamus and medulla oblongata.

NEW FINDINGS: What is the central question of this study? Whether anaphylaxis affects sympathetic outflows to the brown adipose tissue (BAT) and adrenal gland and whether anaphylaxis affects some brain areas in association with sympathetic regulation. What is the main finding and its importance? Sympathoexcitatory responses to anaphylaxis occurred regionally in the kidney and adrenal gland, but not in the thermogenesis-related BAT. Further, anaphylactic hypotension also caused increase in c-fos immunoreactivity in the hypothalamic and medullary areas. Moreover, catecholaminergic neurons of the brainstem cause adrenal sympathoexcitation in a baroreceptor-independent manner. ABSTRACT: We previously reported that sympathetic nerve activity (SNA) to the kidney and the hindlimb increases during anaphylactic hypotension in anaesthetized rats. Based on this evidence, we examined effects of anaphylactic hypotension on SNA to the brown adipose tissue (BAT), and the adrenal gland and kidney in anaesthetized rats. We demonstrated that adrenal and renal SNA, but not BAT-SNA, were stimulated. In addition, the effects of anaphylaxis on neural activities of the hypothalamic and medullary nuclei, which are candidates for relaying efferent SNA to the peripheral organs, were investigated via immunohistochemical staining of c-fos. Anaphylaxis increased c-fos expression in the neurons of the paraventricular nucleus (PVN) of the hypothalamus and in those of the nucleus tractus solitarii (NTS) and rostral ventrolateral medulla (RVLM) of the medulla oblongata; c-fos was expressed in γ-aminobutyric acid (GABA)-ergic neurons of the NTS and in the catecholaminergic neurons of the RVLM. In addition, c-fos expression in the rostral NTS and mid NTS during anaphylaxis was reduced by sinoaortic baroreceptor denervation; however, increased c-fos expression in the caudal NTS and RVLM or adrenal sympathoexcitation were not affected by sinoaortic baroreceptor denervation. These results indicated that anaphylactic hypotension activates the hypothalamic PVN and the medullary NTS and RVLM independently of the baroreflex pathway. Further, it stimulated efferent SNA to the adrenal gland and kidney to restore blood pressure.

Baroreceptors in the carotid and hypertension-systematic review and meta-analysis of the effects of baroreflex activation therapy on blood pressure.

Activation of baroreceptors in the carotid modulates the autonomic nervous system. Baroreflex activation therapy (BAT), which activates baroreceptors in the carotid, has become available in the treatment of resistant hypertension. Besides this, a carotid implant modulating baroreceptors as well as pharmacological modulation of carotid bodies were quite recently presented. This review will underscore currently available and promising approaches that activate baroreceptors in the carotid, and thereby contribute to beneficial effects in patients with arterial hypertension, and discusses potential organoprotective BAT effects beyond blood pressure (BP) reduction. A systematic review and meta-analysis was conducted including observational studies or randomized controlled trials that investigated the effect of BAT on BP in resistant hypertension. Nine studies, seven observational and two randomized, with a total of 444 patients, were included in the evaluation. Analysing the longest follow-up visit from the different studies, there was a significant reduction of systolic BP after BAT of -36 mmHg [95% confidence interval (CI) -42 to -30 mmHg]. Separate meta-analysis of the short-term (1-6 months) and long-term effects (≥12 months) revealed a reduction of -21 mmHg (95% CI -26 to -17 mmHg) and -38 mmHg (95% CI -46 to -30 mmHg), respectively. There are promising data both in the experimental and the clinical application for BAT. Though the present meta-analysis suggests beneficial effects of BAT on BP, the results must be interpreted extremely carefully. Considering that evidence from controlled trials is very limited, it is evident that there is a strong need for further investigation.

Endovascular Baroreflex Amplification for Resistant Hypertension.

PURPOSE OF REVIEW: Most hypertension devices have been designed to interrupt or modify the sympathetic nervous system, which seems to be unbalanced in hypertension. Carotid baroreceptors play a pivotal role in maintaining adrenergic balance via a direct feedback interface and would be an exceptional target for intervention. The purpose of this review is to define the role of the baroreceptor in hypertension, to examine device-based therapies targeting the baroreflex and to explore future promises of endovascular baroreflex amplification (EBA). RECENT FINDINGS: In the last two decades, two therapeutic strategies targeting the carotid baroreceptor have evolved: baroreflex activation therapy (BAT) and EBA. Both therapies enhance baroreceptor activity, either directly by electrical stimulation or indirectly by changing the geometric shape of the carotid sinus and increasing pulsatile wall strain. By showing a significant, sympathetic inhibition-mediated effect on blood pressure, BAT has laid the foundation for baroreflex-targeting therapies for resistant hypertension. EBA is a less invasive therapy with promising first-in-man study results. Ongoing randomized sham-controlled trials are needed to better understand efficacy, durability, and long-term safety and define phenotypes that may most benefit from this treatment.

An early analysis of cost-utility of baroreflex activation therapy in advanced chronic heart failure in Germany.

BACKGROUND: This study aimed to evaluate cost-utility of baroreflex activation therapy (BAT) using the Barostim neo™ device (CVRx Inc., Minneapolis, MN, USA) compared with optimized medical management in patients with advanced chronic heart failure (NYHA class III) who were not eligible for treatment with cardiac resynchronization therapy, from a statutory health insurance perspective in Germany over a lifetime horizon. METHODS: A decision analytic model was developed using the combination of a decision tree and the Markov process. The model included transitions between New York Heart Association (NYHA) health states, each of which is associated with a risk of mortality, hospitalization, cost, and quality of life. The effectiveness of BAT was projected through relative risks for mortality (obtained by application of patient-level data to the Meta-analysis Global Group in Chronic Heart Failure risk prediction model) and hospitalization owing to worsening of heart failure (obtained from BAT Randomized Clinical Trial). All patients were in NYHA class III at baseline. RESULTS: BAT led to an incremental cost of €33,185 (95% credible interval [CI] €24,561-38,637) and incremental benefits of 1.78 [95% CI 0.45-2.71] life-years and 1.19 [95% CI 0.30-1.81] quality-adjusted life-years (QALYs). This resulted in an incremental cost-effectiveness ratio of €27,951/QALY (95% CI €21,357-82,970). BAT had a 59% probability of being cost-effective at a willingness-to-pay threshold of €35,000/QALY (but 84% at a threshold of €52,000/QALY). CONCLUSIONS: BAT can be cost-effective in European settings in those not eligible for cardiac resynchronization therapy among patients with advanced heart failure.

Baroreceptor Activation Therapy 2 Decades after Vascular Surgery on Both Carotid Arteries in a Patient with Resistant Hypertension: First Case Report in the Literature.

Patients with previous surgery of the carotids or significant stenosis are not included in the study populations of baroreceptor activation therapy (BAT). In this case report about a 78-year-old woman with implantation of a BAT system 2 decades after bilateral thromboendarterectomy, control of hypertensive dysregulation could be observed even 20 months after implantation. Successful modulation of the baroreceptors requires intact adventitial tissue near the carotid sinus. In our case with previous longitudinal incision and patch angioplasty, the nerval innervation had been preserved. After careful evaluation, patients with a history of carotid thromboendarterectomy might be considered for BAT.

Role of Vasopressin in Rat Models of Salt-Dependent Hypertension.

PURPOSE OF REVIEW: Dietary salt intake increases both plasma sodium and osmolality and therefore increases vasopressin (VP) release from the neurohypophysis. Although this effect could increase blood pressure by inducing fluid reabsorption and vasoconstriction, acute activation of arterial baroreceptors inhibits VP neurons via GABAA receptors to oppose high blood pressure. Here we review recent findings demonstrating that this protective mechanism fails during chronic high salt intake in rats. RECENT FINDINGS: Two recent studies showed that chronic high sodium intake causes an increase in intracellular chloride concentration in VP neurons. This effect causes GABAA receptors to become excitatory and leads to the emergence of VP-dependent hypertension. One study showed that the increase in intracellular chloride was provoked by a decrease in the expression of the chloride exporter KCC2 mediated by local secretion of brain-derived neurotrophic factor and activation of TrkB receptors. Prolonged high dietary salt intake can cause pathological plasticity in a central homeostatic circuit that controls VP secretion and thereby contribute to peripheral vasoconstriction and hypertension.