Electrical Stimulation Of Carotid Sinus Nerve Research Articles

Electrical carotid sinus nerve stimulation attenuates experimental colitis induced by acetic acid in rats

AimsThe carotid bodies are sensors that detect physiological signals and convey them to the central nervous system, where the stimuli are processed inducing reflexes through efferent pathways. Recent studies have demonstrated that electrical stimulation of the carotid sinus nerve (CSN) triggers the anti-inflammatory reflex under different conditions. However, whether this electrical stimulation attenuates colitis was never examined. This study aimed to evaluate if the electrical CSN stimulation attenuates the experimental colitis induced by intrarectal administration of acetic acid in rats. MethodsElectrodes were implanted around the CSN to stimulate the CSN, and a catheter was inserted into the left femoral artery to record the arterial pressure. The observation of hypotensive responses confirmed the effectiveness of the electrical CNS stimulation. This maneuver was followed by a 4 % acetic acid or saline administered intrarectally. After 24 h, colons were segmented into distal and proximal parts for macroscopy, histological and biochemical assessment. Key findingsAs expected, the electrical CSN stimulation was effective in decreasing arterial pressure in saline and colitis rats. Moreover, electrical CSN stimulation effectively reduced colonic tissue lesions, colitis scores, and histopathologic parameters associated with colitis. In addition, the CSN stimulation also reduced the colonic mucosa pro-inflammatory cytokine interleukin-1 beta, and increased the anti-inflammatory interleukin-10, in rats submitted to colitis. SignificanceThese findings indicated that electrical CSN stimulation breaks the vicious cycle of local colon inflammation in colitis, which might contribute to its better outcome.

Circulatory control of phrenic motor plasticity

Acute intermittent hypoxia (AIH) elicits distinct mechanisms of phrenic motor plasticity initiated by brainstem neural network activation versus local (spinal) tissue hypoxia. With moderate AIH (mAIH), hypoxemia activates the carotid body chemoreceptors and (subsequently) brainstem neural networks associated with the peripheral chemoreflex, including medullary raphe serotonergic neurons. Serotonin release and receptor activation in the phrenic motor nucleus then elicits phrenic long-term facilitation (pLTF). This mechanism is independent of tissue hypoxia, since electrical carotid sinus nerve stimulation elicits similar serotonin-dependent pLTF. In striking contrast, severe AIH (sAIH) evokes a spinal adenosine-dependent, serotonin-independent mechanism of pLTF. Spinal tissue hypoxia per se is the likely cause of sAIH-induced pLTF, since local tissue hypoxia elicits extracellular adenosine accumulation. Thus, any physiological condition exacerbating spinal tissue hypoxia is expected to shift the balance towards adenosinergic pLTF. However, since these mechanisms compete for dominance due to mutual cross-talk inhibition, the transition from serotonin to adenosine dominant pLTF is rather abrupt. Any factor that compromises spinal cord circulation will limit oxygen availability in spinal cord tissue, favoring a shift in the balance towards adenosinergic mechanisms. Such shifts may arise experimentally from treatments such as carotid denervation, or spontaneous hypotension or anemia. Many neurological disorders, such as spinal cord injury or stroke compromise local circulatory control, potentially modulating tissue oxygen, adenosine levels and, thus, phrenic motor plasticity. In this brief review, we discuss the concept that local (spinal) circulatory control and/or oxygen delivery regulates the relative contributions of distinct pathways to phrenic motor plasticity.

Carotid sinus nerve electrical stimulation in conscious rats attenuates systemic inflammation via chemoreceptor activation

Recent studies demonstrated a critical functional connection between the autonomic (sympathetic and parasympathetic) nervous and the immune systems. The carotid sinus nerve (CSN) conveys electrical signals from the chemoreceptors of the carotid bifurcation to the central nervous system where the stimuli are processed to activate sympathetic and parasympathetic efferent signals. Here, we reported that chemoreflex activation via electrical CSN stimulation, in conscious rats, controls the innate immune response to lipopolysaccharide attenuating the plasma levels of inflammatory cytokines such as tumor necrosis factor (TNF), interleukin 1β (IL-1β) and interleukin 6 (IL-6). By contrast, the chemoreflex stimulation increases the plasma levels of anti-inflammatory cytokine interleukin 10 (IL-10). This chemoreflex anti-inflammatory network was abrogated by carotid chemoreceptor denervation and by pharmacological blockade of either sympathetic - propranolol - or parasympathetic - methylatropine – signals. The chemoreflex stimulation as well as the surgical and pharmacological procedures were confirmed by real-time recording of hemodynamic parameters [pulsatile arterial pressure (PAP) and heart rate (HR)]. These results reveal, in conscious animals, a novel mechanism of neuromodulation mediated by the carotid chemoreceptors and involving both the sympathetic and parasympathetic systems.

Point:Counterpoint: Respiratory sinus arrhythmia is due to a central mechanism vs. respiratory sinus arrhythmia is due to the baroreflex mechanism

Blood pressure and heart periods fluctuate at respiratory frequencies in healthy humans. Some researchers ([8][1], [23][2]) explain this as a cause-and-effect relation: blood pressure changes trigger baroreflex-mediated R-R interval changes. Here I make the case that respiratory sinus arrhythmia is

How to encode arterial pressure into carotid sinus nerve to invoke natural baroreflex

The purpose of this study was to develop an artificial baroreceptor that was capable of invoking the "natural" baroreflex by electrically stimulating the afferent nerve. In six anesthetized, vagotomized dogs, we first identified, using the white-noise method, the transfer function from carotid sinus pressure to aortic pressure (HCSP.AoP) and that from the electrical carotid sinus nerve stimulation to aortic pressure (HCSN.AoP). We then backcalculated the transfer function required for the artificial baroreceptor (HCSP.CSN) as the ratio of HCSP.AoP to HCSN.AoP. To activate the artificial baroreceptor, we electrically stimulated the carotid sinus nerve with the frequency-modulated pulse train obtained in real time by convolving the impulse response of HCSP.CSN with instantaneous aortic pressure. We tested performance of the artificial baroreceptor by imposing random changes in blood volume. The pressure-stabilizing effects of the artificial baroreceptor were indistinguishable from those of the native one. We conclude that the artificial baroreceptor can invoke the natural baroreflex. The proposed framework generally would be applicable to interface artificial devices with the central nervous system.

Changes in blood pressure and heart rate during passive upright tilt upon electrical carotid sinus nerve stimulation

Electrical carotid sinus nerve stimulation was applied in three normotensivve anginal patients and one hypertensive patient during upright tilting. Despite a base-line depressor response to continuous stimulation, orthostatic hypotension was not augmented. In individual patients stimulation slightly enhanced the fall of systolic pressure and delayed the increase of diastolic pressure immediately after tilting. Base-line heart rates and cardio-acceleration upon tilting remained almost uninfluenced by stimulation. It is concluded that a moderately enhanced carotid baroreceptor afferent nerve traffic did not interfere with the regular orthostatis response.

The evolution strategy--a search strategy used in individual optimization of electrical parameters for therapeutic carotid sinus nerve stimulation.

Optimization problems, arising in the search for parameters and/or techniques of functional electrostimulation (FES), disproportionally increase when multiple electrodes, electrode configurations, electrical parameters, and stimulation modes may be applied. When computational or investigational effort precludes systematic studies in FES, we propose to apply and evaluate Rechenberg's evolution strategy, which in technical use and numerical optimization has been valid in comparison to more traditional methods. This strategy implements mutation and selection processes in analogy to biological evolution. The effect of combined multiple input variables on a quality function (Q) is experimentally evaluated. The actual computed value of Q serves as a selection criterion for those input variable combinations which lead Q to approach a target value (maximization), similar to a hill-climbing procedure. In radiofrequency controlled, therapeutic electrical carotid sinus nerve stimulation (CSNS), we varied (mutated) combinations of pulse frequency and pulse amplitude parameters, according to the evolution strategy, in individual patients. CSNS lowers blood pressure and decreases heart rate. Q was computed from blood pressure and heart rate responses to CSNS. The strategy individually optimized electrical parameters to achieve large depressor responses upon CSNS. Although, in contrast to technical usage, only two input variables were investigated, and biomedical experience with the evolution strategy is limited so far, its potential use in other fields of FES, especially when more input variables are to be optimized, is discussed and encouraged.

Search for optimal frequencies and amplitudes of therapeutic electrical carotid sinus nerve stimulation by application of the evolution strategy.

In humans, electrical, bipolar, bilateral carotid sinus nerve stimulation (CSNS; impulse duration 0.35 ms) was applied, using frequencies between 10 and 110 Hz and voltages between individual thresholds and maximal amplitudes of stimulation. Ten anginal patients and two hypertensive patients were studied at an interval of up to 12 years after implantation of electrodes and a radiofrequency receiver for chronic therapeutic CSNS. In search of combinations of frequency and voltage of CSNS, eliciting largest ("optimal") depressor responses of blood pressure and heart rate in the individual patient, Rechenberg's evolution strategy was applied. This strategy simulates mutation and selection of biological evolution. In each patient and on each test stimulation, a value of quality was computed from actual heart rate and blood pressure values as a selection criterion for the strategy. Either responses to uninterrupted CSNS were investigated, while stimulation parameters were adjusted every 3 min, according to the strategy, or responses to 3 min of CSNS after a change in stimulation parameters were compared to intercalated 3-min control periods. In each patient, one or more combined settings of frequency and voltage elicited "optimal" responses. In principle, "optimal" CSNS frequencies ranged between 35 and 105 Hz with large interindividual differences. Due to chronic implantation of electrodes and technical features of radiofrequency transmitted stimulation energy, interindividually different voltages led to an optimal response to CSNS. Also according to the present results, the frequency of CSNS has to be determined individually. It is concluded that the evolution strategy was applied successfully, because voltage and frequency settings leading to "optimal" responses were found within 90-180 min, whereas intraindividual systematic investigations would not be feasible due to their necessarily very long duration. So far, only short-term responses have been evaluated. A broader use of the strategy in other applications is encouraged, as for example in pacemaker optimization and especially in functional electrostimulation.

Blood pressure and heart rate changes during physical activity upon heart rate feedback-controlled electrical carotid sinus nerve stimulation

The effect of feedback-controlled electrical carotid sinus nerve stimulation on changes in blood pressure and heart rate during interventions simulating usual daily activity was studied in four anginal patients. Frequency or amplitude of stimulation was modulated pulse-synchronously and controlled by heart rate. While individual responses differed between both types of modulation, stimulation attenuated predominantly increases in blood pressure during walking and staircase climbing. Heart rate changes remained almost unaffected.

Effects of carotid sinus nerve stimulation at different times in the respiratory and cardiac cycles on variability of heart rate and blood pressure of normotensive and renal hypertensive dogs

It was the purpose of the present study to determine (1) whether or not there exists a common respiratory and cardiac cycle time effect of the baroreceptor control of heart rate (HR) and blood pressure (BP) in spontaneously breathing anaesthetized dogs and (2) whether this effect, if present, is abnormal in dogs with renal hypertension. The baroreflex responses were evoked by brief low-intensity electrical carotid sinus nerve stimulation (CSNS) triggered by the R-wave in the electrocardiogram with an adjustable delay (0–210 ms) and positioned in either inspiration or expiration. All baroreceptor afferent nerves were intact. Brief CSNS had no noticeable effect on breathing. The responses of means of HR, respiratory sinus arrhythmia (RSA), and systolic and diastolic respiratory blood pressure waves (RBPW syst, RBPW diast) to CSNS were not different for normotensive and hypertensive dogs. No cardiac, but a small respiratory cycle time effect on means of HR, BP syst and BP diast was observed. The magnitude of RSA and RBPW diast was markedly enhanced for expiratory CSNS at each delay after the R-wave. Inspiratory CSNS diminished the magnitude of RSA and RBPW only if applied during systole, and become ineffective for delays greater than 200 ms after the R-wave. During both respiratory phases, CSNS was elevated at times of central presentation of the natural sinoaortal baroreceptor discharges (120 ms and 70 ms, respectively). The magnitudes of RSA and RBPW were influenced simultaneously and in the same way by CSNS throughout. It is concluded that, under the present experimental conditions, RSA and RBPW have a common central origin.

11 Blood Pressure Response to Exercise During Antihypertensive Treatment with Electrical Carotid Sinus Nerve Stimulation

11 Blood Pressure Response to Exercise During Antihypertensive Treatment with Electrical Carotid Sinus Nerve Stimulation

The principle of electrical carotid sinus nerve stimulation: a nerve pacemaker system for angina pectoris and hypertension therapy.

Electrical carotid sinus nerve stimulation (CSNS) via an implanted electrode receiver assembly, radio frequency coupled to an external signal generator, is an experimental therapy for hypertension and angina pectoris. CSNS increases afferent information to the central nervous system exerting neurally regulated decreases in heart rate, stroke volume, and blood pressure. No nonspecific side effects are observed, in contrast to drug therapy. A nerve pacemaker system is described and compared to the commonly used open-loop stimulator system (fixed frequency and intensity CSNS). It is a closed-loop system, controlled by heart rate (as an indicator of the state of “arousal” and of sympathetic activity) and, thereby, feedback-controlled by its therapeutic effects. The miniaturized (hybrid technology) system consists of an ECG amplifier, a stimulus pattern memory with I-O periphery and a transmitter, including an antenna coil to be coupled to the implanted assembly. Stimulus parameters (frequency and amplitude of impulses) are optimized for each patient individually. Stimulus patterns (pulse synchronous amplitude modulated groups of impulses) are adapted to the patient's cardiovascular situation. The nerve pacemaker may be an alternative to drug therapy or major surgery in both diseases. Compatible with the open-loop system, it replaces the first step in previously treated CSNS patients.

Closed-loop control of the cardiovascular system by means of an electronic baroreceptor analog

In baropacing (e.g. therapeutical electrical carotid sinus nerve stimulation in open loop, as well as in closed loop by means of a baroreceptor analog) an adaptation of stimulation parameters to the individual patients sensitivity is useful, regarding optimal stimulation patterns. An alternative method to closed loop frequency modulated stimulation has been developed: Amplitude modulated stimulation was compared to other methods in animal experiments and was found to be equally effective to frequency modulation with regard to depressor response. With regard to applied stimulation energy, amplitude modulation was found to be energetically more economic. A test unit, comprising currently available stimulation methods has been developed in order to adapt method and stimulation parameters to the needs of a patient to be equipped with a stimulator. An alternative use of the analog is proposed in the control of the artificial heart.

Action potential configuration and contractile response during paired stimulation

Action potential configuration and contractile response during paired stimulation

Treatment of Angina Pectoris by Electrical Stimulation of Carotid-Sinus Nerves

Epstein, S E; Beiser, G D; Goldstein, R E; Redwood, D; Rosing, D R; Glick, G; Wechsler, A S; Stampfer, M; Cohen, L S; Reis, R L; Braunwald, N S; Graunwald, E Author Information

Braunwald NS: Treatment of paroxysmal supraventricular tachycardia by electrical stimulation of the carotid-sinus nerves.

SUPRAVENTRICULAR tachycardia may be terminated by manual pressure on the carotid sinuses or by the administration of parasympathomimetic or of pressor agents. Recently developed technics for the treatment of angina pectoris by electrical stimulation of carotid-sinus nerves in man by means of implanted radiofrequency pacemakers1 2 3 4 provide a way of reflexly increasing vagal activity and withdrawing sympathetic drive to the heart. This communication describes the application of electrical stimulation of the carotid-sinus nerves to a patient with refractory, recurrent supraventricular tachycardia and documents the efficacy of this technic in promptly terminating recurrent attacks.Case ReportC.W. (U.H.S.D.C. 441780), a 69-year-old man, . . .