Electrical Stimulation Of Carotid Sinus Research Articles

Efficacy of Electrical Baroreflex Activation Is Independent of Peripheral Chemoreceptor Modulation.

Arterial baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of resistant hypertension. Previous studies suggested that the peripheral chemoreflex is tonically active in hypertensive patients and may inhibit baroreflex responses. We hypothesized that peripheral chemoreflex activation attenuates baroreflex efficacy evoked by electrical carotid sinus stimulation. We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients with consistent acute depressor response were selected (7 men/4 women, age: 67±8 years, body mass index: 31.6±5.2 kg/m2, 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO2: 79.0±1.5%), and hyperoxia (40% end-tidal O2 fraction) by measuring heart rate, blood pressure, ventilation, oxygen saturation, end-tidal CO2 and O2 fractions, and muscle sympathetic nerve activity. During normoxia, baroreflex activation reduced systolic blood pressure from 164±27 to 151±25 mm Hg (mean±SD, P<0.001), heart rate from 64±13 to 61±13 bpm (P=0.002), and muscle sympathetic nerve activity from 42±12 to 36±12 bursts/min (P=0.004). Hypoxia increased systolic blood pressure 8±12 mm Hg (P=0.057), heart rate 10±6 bpm (P<0.001), muscle sympathetic nerve activity 7±7 bursts/min (P=0.031), and ventilation 10±7 L/min (P=0.002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions: systolic blood pressure: -15±7 versus -14±8 mm Hg (P=0.938), heart rate: -2±3 versus -2±2 bpm (P=0.701), and muscle sympathetic nerve activity: -6±4 versus -4±3 bursts/min (P=0.531). We conclude that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy in patients with resistant hypertension. These patients provided insight into human baroreflex-chemoreflex interactions that could not be gained otherwise.

The Efficacy of Electrical Baroreflex Activation Therapy is Independent of Peripheral Chemoreceptor Modulation

IntroductionBaroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of patients with arterial hypertension not sufficiently responding to pharmacological therapy. Previous studies suggested that peripheral chemoreflex afferents located in proximity to carotid baroreceptors are tonically active in hypertensive patients and may inhibit baroreflex responses. Therefore, we hypothesized that peripheral chemoreflex activation attenuates the efficacy of electrical carotid sinus stimulation.MethodsWe screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients exhibited a consistent acute depressor response and were included in the study (7 men/4 women, age: 67±8 years, BMI: 31.6±5.2 kg/m2, 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO2: 79.0±1.5%), and hyperoxia (40% end‐tidal O2 fraction) by recording ECG, blood pressure (SBP), ventilation, SpO2, end‐tidal CO2 and O2 fractions, and muscle sympathetic nerve activity (MSNA).ResultsDuring normoxia, baroreflex activation reduced SBP from 164±27 to 151±25 mmHg (means±SD, p&lt;0.001), HR from 64±13 to 61±13 bpm (p=0.002), and MSNA from 42±12 to 36±12 bursts/min (p=0.004). Hypoxia increased SBP 8±12 mmHg (p=0.057), HR 10±6 bpm (p&lt;0.001), MSNA 7±7 bursts/min (p=0.031), and ventilation 10±7 l/min (p=0. 002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions; SBP: −15±7 vs −14±8 mmHg (p=0.938), HR: −2±3 vs −2±2 bpm (p=0.701), and MSNA: −6±4 vs −4±3 bursts/min (p=0.531).ConclusionThe main finding of our study is that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy (BAT) in patients with resistant hypertension. These patients provide insight in human baroreflex physiology and baroreflex‐chemoreflex interactions that could not be gained otherwise.Support or Funding InformationFinancial support by Boston Scientific Corporation (St. Paul, MN, U.S.A.)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hemodynamic responses to magnetic stimulation of carotid sinus in normotensive rabbits.

Carotid baroreflex plays a crucial role in regulating arterial pressure. Based on this knowledge, electrical stimulation of carotid sinus was designed for treating resistant hypertension. However, the clinical implication of electrical stimulation of carotid sinus is largely restrained due to obvious invasiveness. This study aimed to evaluate the efficacy of magnetic stimulation of carotid sinus (MSCS), a noninvasive strategy, for lowering blood pressure in rabbits. MSCS with graded intensities and frequencies were systematically attempted in normotensive rabbits. Blood pressure was recorded dynamically. Sinoaortic denervation and plasma hormone level analyses were performed. When the right carotid sinus was stimulated at 1 Hz frequency, a dose-effect relationship was observed between stimulation intensity (100-250% motor threshold) and mean arterial pressure (MAP) decrement (3.6 ± 1.0 to 10.4 ± 2.3 mmHg). When stimulation intensity was fixed at 200% motor threshold, the median reduction of MAP in 1-Hz group [10.8 (8.6-14.9) mmHg] was significantly higher than that in other frequency groups (all P < 0.05). Heart rates declined transiently after the initiation of MSCS. Compared with baseline (33.9 ± 5.5 pg/ml), plasma epinephrine level increased during MSCS (88.1 ± 9.6, P = 0.002). After ipsilateral sinoaortic denervation, MAP decrement (7.0 ± 0.8 mmHg) was remarkably blunted compared with that in sham animals (13.0 ± 1.1 mmHg, P = 0.001). The current study demonstrated that MSCS treatment can lower the arterial pressure in normotensive rabbits. This preliminarily result warrants further studies to establish the efficacy of MSCS in treating refractory hypertension.

Device-Based Approaches for the Treatment of Arterial Hypertension.

Device-based antihypertensive treatments have primarily been developed and clinically tested for patients with hypertension refractory to pharmacological treatment. Most but not all device-based treatments target the sympathetic nervous system and provided important new insight in the mechanisms of human hypertension. This review provides an overview on the scientific rational and clinical data on recent device-based antihypertensive treatment approaches. Device-based treatments targeting the sympathetic nervous system include catheter-based renal nerve ablation, electrical carotid sinus stimulation, modulation of baroreflex transduction through a dedicated carotid stent, carotid body denervation, and deep brain stimulation. Creation of a defined arteriovenous stent with a coupler device and removal of stimulatory antibodies against alpha adrenoreceptors have also been tested. The clinical evidence differs from therapy to therapy with the largest dataset for renal nerve ablation followed by electrical carotid sinus stimulation. Yet, none has been proven efficacious in sham-controlled clinical trials, and none has been shown to reduce cardiovascular morbidity or mortality. Before efficacy is proven, these treatments should not be part of routine medical care and only be applied in the setting of clinical studies.

Intravascular electrical stimulation of carotid sinus augments baroreflex and decreases arterial pressure in an anesthetized dog

Intravascular electrical stimulation of carotid sinus augments baroreflex and decreases arterial pressure in an anesthetized dog

Acute Response to Unilateral Unipolar Electrical Carotid Sinus Stimulation in Patients With Resistant Arterial Hypertension.

Bilateral bipolar electric carotid sinus stimulation acutely reduced muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in patients with resistant arterial hypertension but is no longer available. The second-generation device uses a smaller unilateral unipolar disk electrode to reduce invasiveness while saving battery life. We hypothesized that the second-generation device acutely lowers BP and MSNA in treatment-resistant hypertensive patients. Eighteen treatment-resistant hypertensive patients (9 women/9 men; 53±11 years; 33±5 kg/m(2)) on stable medications have been included in the study. We monitored finger and brachial BP, heart rate, and MSNA. Without stimulation, BP was 165±31/91±18 mm Hg, heart rate was 75±17 bpm, and MSNA was 48±14 bursts per minute. Acute stimulation with intensities producing side effects that were tolerable in the short term elicited interindividually variable changes in systolic BP (-16.9±15.0 mm Hg; range, 0.0 to -40.8 mm Hg; P=0.002), heart rate (-3.6±3.6 bpm; P=0.004), and MSNA (-2.0±5.8 bursts per minute; P=0.375). Stimulation intensities had to be lowered in 12 patients to avoid side effects at the expense of efficacy (systolic BP, -6.3±7.0 mm Hg; range, 2.8 to -14.5 mm Hg; P=0.028 and heart rate, -1.5±2.3 bpm; P=0.078; comparison against responses with side effects). Reductions in diastolic BP and MSNA (total activity) were correlated (r(2)=0.329; P=0.025). In our patient cohort, unilateral unipolar electric baroreflex stimulation acutely lowered BP. However, side effects may limit efficacy. The approach should be tested in a controlled comparative study.

Side effects limit acute efficacy of unilateral unipolar electrical carotid sinus stimulation in patients with treatment resistant arterial hypertension

Side effects limit acute efficacy of unilateral unipolar electrical carotid sinus stimulation in patients with treatment resistant arterial hypertension

Abstract P152: Acute Effect of Unilateral Unipolar Electrical Carotid Sinus Stimulation in Patients with Treatment-Resistant Arterial Hypertension

Electrical carotid sinus stimulation has been developed for treatment of resistant arterial hypertension. The first-generation device (Rheos™) relying on bilateral placement of bipolar electrodes acutely reduced muscle sympathetic nerve activity (MSNA) and blood pressure (BP) but is no longer available. The second-generation device (Neo™) utilizes a smaller unilateral unipolar disk electrode to reduce invasiveness while saving battery life. We tested acute effects of the latter on BP and MSNA. We studied 18 treatment-resistant hypertensive patients (9 women, 53±11 years, 34±5 kg/m 2 ) on stable medication who had been implanted with the second-generation device. We assessed acute BP (oscillometry), heart rate (HR, ECG), and MSNA (microneurography) responses to electrical stimulation in the supine position. Without stimulation, BP was 165±31/91±18 mmHg, HR was 75±17 bpm, and MSNA was 48±14 bursts/min. Acute stimulation with intensities producing side effects that were tolerable in the short term elicited variable changes in systolic BP (SBP: -16.9±15.0 mmHg, range: 0.0 to -40.8 mmHg, p=0.002), HR (-3.6±3.6 bpm, p=0.004), and MSNA (-1.9±5.3 bursts/min, p=0.194). Stimulation intensities had to be lowered in 12 patients to avoid side effects at the expense of efficacy (SBP: -6.3±7.0 mmHg, range: 2.8 to -14.5 mmHg, p=0.028; HR: -1.5±2.3 bpm, p=0.078; comparison against responses with side effects). Reductions in diastolic BP and MSNA (total activity) tended to be correlated (r 2 =0.202, p=0.093). In our patient cohort, unilateral unipolar electrical baroreflex stimulation acutely lowered BP. Side effects may limit efficacy. The novel approach should be tested in a controlled comparative study.

Electrical carotid sinus stimulation: chances and challenges in the management of treatment resistant arterial hypertension.

Treatment resistant arterial hypertension is associated with excess cardiovascular morbidity and mortality. Electrical carotid sinus stimulators engaging baroreflex afferent activity have been developed for such patients. Indeed, baroreflex mechanisms contribute to long-term blood pressure control by governing efferent sympathetic and parasympathetic activity. The first-generation carotid sinus stimulator applying bilateral bipolar stimulation reduced blood pressure in a controlled clinical trial but nevertheless failed to meet the primary efficacy endpoint. The second-generation device utilizes smaller unilateral unipolar electrodes, thus decreasing invasiveness of the implantation while saving battery. An uncontrolled clinical study suggested improvement in blood pressure with the second-generation device. We hope that these findings as well as preliminary observations suggesting cardiovascular and renal organ protection with electrical carotid sinus stimulation will be confirmed in properly controlled clinical trials. Meanwhile, we should find ways to better identify patients who are most likely to benefit from electrical carotid sinus stimulation.

Electrical Stimulation of Carotid Sinus in Conscious Normotensive and Spontaneously Hypertensive Rats

Electrical stimulation (ES) of the carotid sinus (CS) has been used to treat resistant arterial hypertension. Our aim was to evaluate, in conscious normotensive and spontaneously hypertensive rats (SHR), the effect of sustained (60 min) ES of CS on arterial pressure (AP), heart rate (HR) and heart rate variability (HRV). Male Wistar rats (n=8) and SHR (n=8) had the left CS surrounded by a pair of electrodes and insulated from adjacent tissues. A catheter was introduced into the femoral artery and exteriorized together with the CS electrodes. On the next day, conscious rats under continuous recording of AP had their CS stimulated with square pulses of 1 mA, 1 ms, and 30 Hz, delivered randomly, continuously or intermittently (20/20 s ON/OFF), during 60 min. On the following day the type of CS stimulation was inverted. To analyze HRV, segments of 5 min were selected immediately before, at the onset, middle and end of ES period. Greater sustained fall in AP due to ES of CS was observed in SHR (‐50±7 vs ‐11±2 mmHg). A conspicuous bradycardia was also elicited by sustained ES of the CS (‐62±15 and ‐32±11 bpm in SHR and Wistar rats). No difference was observed between continuous or intermittent ES of CS. Overall, HRV was increased by ES of CS only in SHR (from 4.8±0.6 to 11.7±3.2, 7.0±0.6 and 6.7±1.0 bpm at the onset, middle and end of ES). Surprisingly, no differences were observed in HR spectra during ES of CS in both groups. We conclude that ES of the CS was more effective to reduce AP and HR in SHR as compared to normotensive rats. Moreover, despite a marked effect of ES in overall HRV in SHR, no changes in HR spectra were observed.Financial Support: FAPESP, CAPES and CNPq.

Resistente Hypertonie

When blood pressure is poorly controlled despite treatment with a diuretic and two antihypertensive drugs at adequate doses, the hypertension is termed resistant. The prevalence of resistant hypertension is increasing. Once pseudo-resistance due to poor compliance, secondary forms of hypertension, and massive salt consumption have been excluded, some authorities maintain that blood pressure can be invariably lowered using minoxidil or mineralocorticoid receptor blockade. I also adhered to this belief until we encountered a patient who despite treatment with seven antihypertensive agents, electrical carotid sinus stimulation, and catheter-based renal denervation continued to exhibit extraordinarily high blood pressure values. I am now convinced that resistant hypertension does indeed exist. The prevalence of such patients can be substantially reduced by means of a thorough history and physical examination, determining drug serum concentrations, and excluding secondary causes.

Rebuttal from Markus P. Schlaich, Yusuke Sata and Murray D. Esler.

Extreme positions are rarely useful and almost invariably hinder rather than facilitate progress in clinical science. Dr Jordan (Jordan, 2014) and Dr Paton (Ratcliffe et al. 2014) and their colleagues seem to share this view and, while making a strong case for each of their points, have provided a reasonably balanced appraisal of the evidence surrounding the interventional approaches for resistant hypertension under debate. Importantly, we seem to share common ground in the view that resistant hypertension is a relevant clinical problem, that non-adherence to prescribed medication is common, that alternative and perhaps device-based therapeutic approaches are needed, and that sympathetic overactivity is a major contributor to the pathophysiology of resistant hypertension thereby providing a logical therapeutic target. Our views differ in how this is best achieved. Dr Jordan elegantly reviews the role of baroreflex circuits in long-term blood pressure (BP) control and how electrical carotid sinus stimulation (CCS) may ameliorate resistant hypertension. While highlighting potential advantages of CCS such as the ability of stimulation adjustment, it becomes clear from his pathophysiological considerations that sympathetic inhibition, specifically suppression of efferent renal sympathetic nerve activity, is an important mediator of CCS-induced depressor responses (Iliescu et al. 2012). Why not target the renal nerves directly when this can be achieved safely with catheter-based approaches (Esler et al. 2010; Bhatt et al. 2014)? Carotid body (CB) denervation is the least developed and investigated approach, which does not negate the physiological relevance of chemoreceptor activation and its role in modulation of both sympathetic nerve activity and blood pressure. Dr Paton promotes the concept of CB tonicity driving sympathetic vasomotor activity chronically, particularly in the scenario of hypertension (Paton et al. 2013). Surgical resection of the CB has been performed to alleviate dyspnoea in patients with obstructive airway disease and coincidentally, a BP reduction was observed in a subgroup of hypertensive patients (Nakayama, 1961). Clearly, recent experimental data is more convincing (McBryde et al. 2013). Nevertheless, evidence for a pivotal role of CB-related mechanisms in human resistant hypertension is weak and the concept far from proven. Major concerns that need to be addressed relate to the potential attenuation or loss of hypoxic ventilatory drive and the potentially serious procedural complications. In keeping with the hypothetical ideals for an interventional approach brought forward by Dr Paton, we would argue that renal denervation remains the most promising therapeutic approach despite the recent setback from a suboptimally conducted clinical trial (Bhatt et al. 2014).

Rebuttal from Jens Jordan.

The new interventional treatments discussed in this CrossTalk debate address fundamental physiological mechanisms regulating autonomic nervous system activity and blood pressure, namely renal innervation, peripheral chemoreceptors, or carotid baroreflexes. The solid physiological rationale behind catheter-based renal denervation (Ratcliffe et al. 2014) and carotid chemoreceptor denervation/modulation (Schlaich et al. 2014) has been reviewed by a group of internationally recognized experts in the field. There is not much I could add. I would argue that catheter-based renal denervation, carotid chemoreceptor denervation/modulation and electrical carotid sinus stimulation deserved to undergo rigorous clinical testing. However, the road from a good idea to an effective treatment that can be incorporated into routine clinical care is a long one. Both Ratcliffe et al. (2014) and Schlaich et al. (2014) suggest that silver bullet interventional cures are unlikely. I could not agree more. Interventional treatments for resistant primary hypertension may simply fail for technical reasons. The technology ought to be improved and we should find ways to identify technical failure early on. More importantly, there are pathophysiological reasons why not all patients will respond to a treatment lowering blood pressure through sole manipulation of sympathetic nervous system activity. The statement by Schlaich et al. (2014) that sympathetic activation is the hallmark of arterial hypertension is somewhat misleading. Instead, the contribution of sympathetic activity to arterial hypertension appears to vary from patient to patient. We applied pharmacological ganglionic blockade, which acutely abolishes sympathetic and parasympathetic efferent activity, to gauge autonomic nervous system contributions to primary hypertension in an earlier study (Jordan et al. 2002). In some patients, blood pressure remained elevated during ganglionic blockade. Similarly, in rare patients with near complete loss of peripheral autonomic nerves and supine hypertension, blood pressure remains elevated during ganglionic blockade (Shannon et al. 2000). Sympathetic inhibition cannot control blood pressure in all patients. The column heading in the paper by Schlaich et al. stating that catheter-based renal denervation is safe and effective may be a little too optimistic. The fact that the procedure did not lower blood pressure in Simplicity-3 compared to rigorous controls cannot be neglected. In the past, European regulations permitted approval of devices in the absence of true efficacy data. The company producing a device had to show that operator and patient are not harmed and that the device serves its stated purpose. Data from smaller-scaled studies without a rigorous control group were sufficient for the agencies. Arterial stents served the stated purpose abolishing atherosclerotic renal artery stenosis. However, they failed miserably in controlling hypertension (Cooper et al. 2014). The scientific community should be smarter by now and not accept treatments that have not been proven useful in sufficiently large and well-controlled clinical trials. Finally, procedures should be tested with the same rigor as tablet-based interventions. Simplicity-3 (Bhatt et al. 2014) was exemplary in that regard.

Limited Acute Influences of Electrical Baroreceptor Activation on Insulin Sensitivity and Glucose Delivery: A Randomized, Double-Blind, Crossover Clinical Study

Arterial baroreflexes may regulate resistance vessels supplying glucose to skeletal muscle by modulating efferent sympathetic nervous system activity. We hypothesized that selective manipulation of baroreflex activity through electrical carotid sinus stimulation influences insulin sensitivity by changing muscular glucose delivery. We enrolled 16 hypertensive patients who responded to treatment with an electrical carotid sinus stimulator. Patients were submitted to a frequently sampled intravenous glucose tolerance test (FSIGT) with the stimulator on and with the stimulator off on separate days in a randomized, double-blind, crossover study. We monitored interstitial glucose, lactate, and pyruvate in the vastus lateralis muscle using microdialysis. Glucose and insulin concentrations in arterialized venous blood before and during FSIGT were virtually identical with the stimulator on and with the stimulator off. Insulin sensitivity, the primary end point of this study, was 3.3 ± 1.0 (mU/L)(-1) ⋅ min(-1) and 4.4 ± 2.6 (mU/L)(-1) ⋅ min(-1) (on vs. off; P = 0.7). Interstitial glucose, lactate, and pyruvate increased similarly during FSIGT regardless of the stimulator settings. In conclusion, acute changes in baroreceptor stimulation did not elicit significant changes in muscular glucose delivery and whole-body insulin sensitivity. Baroreflex-mediated changes in sympathetic vasomotor tone may have a limited acute effect on muscle glucose metabolism in patients with treatment-resistant hypertension.

Hemodynamic responses to electrical stimulation of carotid sinus in conscious rats (1169.15)

Carotid sinus (CS) is an important site of arterial baroreceptors and its electrical stimulation has been used to treat patients with resistant hypertension. This study evaluated hemodynamic responses to electrical stimulation of CS in normal conscious rats. Rats (N=5) had left carotid sinus (CS) carefully isolated, equipped with a pair of electrodes and insulated with a layer of Kwik sil. A catheter was introduced into abdominal aorta throughout laparotomy and exteriorized in the back of the neck, together with the CS electrodes. After two days, conscious rats, under continuous recording of AP and HR, had their CS electrically stimulated, during 20 s, with square pulses of 2 ms, 1 mA and 15, 30, 60 and 90 Hz. Rats showed a basal arterial pressure (AP) and heart rate (HR) of 108±3 mmHg and 353±9 bpm. The recorded voltage of the 1 mA pulses allowed the calculation of carotid sinus resistance that ranged from 4.3 to 7.2 kΩ. A fall in mean AP (Δ=19±2, 28±7, 31±4 and 39±4 mmHg) was observed 5‐9 s after the onset of carotid sinus stimulation with 15, 30, 60 and 90 Hz, respectively. A slight and non‐statistically significant fall in HR (9‐35 bpm) was also observed immediately (1‐3 s) after the onset of CS stimulation. In contrast to electrical stimulation of aortic nerve in conscious rats, currently performed in our lab, CS stimulation affected mainly vascular resistance, once only a slight and non‐significant effect was seem in HR.Grant Funding Source: Supported by CAPES, FAPESP, CNPq.

Research needs in the area of device-related treatments for hypertension

Hypertension is the primary risk factor for cardiovascular and renal-disease endpoints. Medications help many patients but not all. Recently, two device-related treatments have been introduced, catheter-based renal denervation and electrical carotid sinus stimulation. Remuneration for these treatments is guaranteed in many countries even though basic information is missing. We draw attention to deficiencies in the database. For catheter-based renal denervation, few large-animal data are available to investigate the effect of the intervention on the histology of the arterial wall. No functional data are available regarding re-innervation. For carotid sinus stimulation, the situation is similar. Acute activation of either treatment seems to reduce sympathetic tone dramatically. However, whether or not the effects are sustained over time is unknown. No 'end-point' data are available for either treatment. Devices should be subjected to evidence-based standards before widespread introduction.

Electrical carotid sinus stimulation in treatment resistant arterial hypertension

Treatment resistant arterial hypertension is commonly defined as blood pressure that remains above goal in spite of the concurrent use of three antihypertensive agents of different classes. The sympathetic nervous system promotes arterial hypertension and cardiovascular as well as renal damage, thus, providing a logical treatment target in these patients. Recent physiological studies suggest that baroreflex mechanisms contribute to long-term control of sympathetic activity and blood pressure providing an impetus for the development of electrical carotid sinus stimulators. The concept behind electrical stimulation of baroreceptors or baroreflex afferent nerves is that the stimulus is sensed by the brain as blood pressure increase. Then, baroreflex efferent structures are adjusted to counteract the perceived blood pressure increase. Electrical stimulators directly activating afferent baroreflex nerves were developed years earlier but failed for technical reasons. Recently, a novel implantable device was developed that produces an electrical field stimulation of the carotid sinus wall. Carefully conducted experiments in dogs provided important insight in mechanisms mediating the depressor response to electrical carotid sinus stimulation. Moreover, these studies showed that the treatment success may depend on the underlying pathophysiology of the hypertension. Clinical studies suggest that electrical carotid sinus stimulation attenuates sympathetic activation of vasculature, heart, and kidney while augmenting cardiac vagal regulation, thus lowering blood pressure. Yet, not all patients respond to treatment. Additional clinical trials are required. Patients equipped with an electrical carotid sinus stimulator provide a unique opportunity gaining insight in human baroreflex physiology.

Go for the cardiovascular ‘physionom’

Go for the cardiovascular ‘physionom’

Parabrachial units responding to stimulation of buffer nerves and forebrain in the cat.

Spontaneously firing units in the region of parabrachial nuclei (PB) and Kölliker-Fuse nuclei (KF) of 19 chloralose-anesthetized cats were monitored for changes in firing frequency during electrical stimulation of carotid sinus (CSN) and aortic depressor (ADN) nerves, of central nucleus of the amygdala (ACE), and of paraventricular nuclei of the hypothalamus (PVH). In the ipsilateral PB 64 of 189 and in the contralateral PB 9 of 103 units responded to CSN stimulation; 18 of 185 ipsilaterally and 7 of 97 contralaterally responded to ADN stimulation. Responses were primarily excitatory, and units were located primarily in the ventrolateral portion of the PB. Only 9 of 267 units responded to stimulation of both CSN and ADN. Stimulation of the ACE and PVH antidromically activated 9 and 7 units, respectively, in PB and approximately half of these also responded to buffer nerve stimulation. In the ipsilateral PB 56 of 207 and in the contralateral PB 11 of 103 units responded orthodromically to ACE stimulation, and 23 of 177 ipsilaterally and 2 of 103 contralaterally responded orthodromically to PVH stimulation with primarily excitatory responses and were located primarily in the ventrolateral portion of the PB and KF. Of these units approximately half also responded to buffer nerve stimulation. These results suggest an important role for PB-KF in mediating ascending and descending cardiovascular and respiratory control signals.

Renal afferent nerves affect discharge rate of medullary and hypothalamic single units in the cat.

Abstract Electrical activity of spontaneously firing single units in the medulla and hypothalamus of 22 cats anesthetized with chloralose was monitored for changes in firing frequency during electrical stimulation of afferent renal (ARN) and carotid sinus (CSN) nerves. Stimulation of ARN altered the firing frequency of 214 out of 540 units studied in the ipsi- and contralateral medulla; the majority of the responses were excitatory but a few units (8%) were inhibited by stimulation. Of the units responding to ARN stimulation, 57% were found to respond in the same manner to stimulation of the CSN. Responsive units were found primarily in 3 regions: the lateral tegmental field, the area of the paramedian reticular nucleus and the region of the dorsal vagal complex around the obex. In the hypothalamus stimulation of ARN affected the activity of 197 of the 407 units studied ipsi- and contralaterally; the majority of the units were excited but 8% were found to be inhibited. Of the units responding to ARN 75% also responded to stimulation of the CSN. Responsive units were found in most areas but were concentrated in 3 anterior regions: lateral preoptic area, lateral hypothalamic area and the region of the paraventricular nucleus. This is the first demonstration that stimulation of afferent renal nerves can influence the electrical activity of medullary and hypothalamic neurons bilaterally. Because of the demonstrated physiological role of the structures where these responsive units were found these results suggest that sensory receptors in the kidney convey important information to central sites involved in physiological responses related to cardiovascular adjustments and fluid balance. Furthermore it has been demonstrated that the majority of medullary and hypothalamic neurons responding to stimulation of ARN also receive an input from the CSN suggesting that certain regions of both medulla and hypothalamus can integrate peripheral information from the kidney and from cardiovascular receptors to bring about appropriate homeostatic responses.