Autonomic Nerve Stimulation Research Articles

Intraoperative pelvic neuromonitoring based on bioimpedance signals: a new method analyzed on 30 patients

PurposeIncreasing importance has been attributed in recent years to the preservation of the pelvic autonomic nerves during rectal resection to achieve better functional results. In addition to improved surgical techniques, intraoperative neuromonitoring may be useful.MethodsThis single-arm prospective study included 30 patients who underwent rectal resection performed with intraoperative neuromonitoring by recording the change in the tissue impedance of the urinary bladder and rectum after stimulation of the pelvic autonomic nerves. The International Prostate Symptom Score, the post-void residual urine volume and the Low Anterior Resection Syndrome Score (LARS score) were assessed during the 12-month follow-up period.ResultsA stimulation-induced change in tissue impedance was observed in 28/30 patients (93.3%). In the presence of risk factors such as low anastomosis, neoadjuvant radiotherapy and a deviation stoma, an average increase of the LARS score by 9 points was observed 12 months after surgery (p = 0,04). The function of the urinary bladder remained unaffected in the first week (p = 0,7) as well as 12 months after the procedure (p = 0,93).ConclusionThe clinical feasibility of the new method for pelvic intraoperative neuromonitoring could be verified. The benefits of intraoperative pelvic neuromonitoring were particularly evident in difficult intraoperative situations with challenging visualization of the pelvic nerves.

Closed-Loop Multimodal Neuromodulation of Vagus Nerve for Control of Heart Rate.

The use of electrical current to modulate neurons for autonomic regulation requires the ability to both up-regulate and down-regulate the nervous system. An implanted system employing this electrical neuromodulation would also need to adapt to changes in autonomic state in real-time. Stimulation of autonomic nerves at frequencies in the range 1-30 Hz has been a well-established technique for increasing neural activity. Vagus nerve stimulation (VNS) has been shown to be sensitive to frequency adjustments, which can be used to more precisely control the effect as compared to amplitude modulation. Kilohertz frequency alternating current (KHFAC) is a proven technique for blocking action potential conduction to reduce neural activity. Additionally, KHFAC can be reliably modulated by simple amplitude modulation. Although there are many types of commonly used closed-loop controllers, many conventional methods do not respond well to long system delays or discontinuities. Fuzzy logic control (FLC) is a state-based controller that can describe the discontinuities of the system linguistically and then translate the state transition to a continuous output signal. In our preparation, a single bipolar electrode was placed on the vagus nerve and controlled by a fuzzy logic controller to deliver both stimulation and KHFAC to control heart rate. The FLC was able to both change the heart rate to selected values and maintain the heart rate at a constant value in response to a physiological perturbation.

The Effect of Epipharyngeal Abrasive Therapy (EAT) on the Baroreceptor Reflex (BR).

Introduction Epipharyngeal Abrasive Therapy (EAT) has been used as a treatment for chronic epipharyngitis, and although autonomic nerve stimulation has been pointed out as one of the mechanisms by which EAT produces therapeutic effects, there have been few reports examining this mechanism of action. This study investigated the effects of repeated EAT on autonomic nervous system activity in chronic epipharyngitis patients over time, using heart rate variability analysis. In addition, we conducted a loading test using the active standing test (AS test) to examine the effects of EAT on the baroreceptor reflex (BR). Subjects and methods A retrospective study was conducted on 39 patients who visited our clinic between July 2017 and November 2019 and underwent autonomic function tests with a diagnosis of chronic nasopharyngeal inflammation. The subjects were divided into two groups: the improvement group and the invariant group for comparison.Electrocardiographic recordings and blood pressure measurements were made under the stress of the AS test. Heart rate, high-frequency (HF) component, low-frequency (LF) component, and Coefficient of Variation on R-R interval were evaluated as indices of autonomic function.Component coefficient of variance high frequency was used as an index of parasympathetic function. ccvLF/ccvHF ratio was calculated by dividing the component coefficient of variance low frequency by ccvHF. The AS test was conducted in phase 1 in the initial resting sitting position, in phase 2 in the standing position, in phase 3 in the standing and holding the standing position, and in phase 4 in the seated and holding the sitting position. Systolic blood pressure, mean arterial pressure, and diastolic blood pressure were obtained in each phase.A paired t-test was used to compare the improved and invariant groups before and after treatment. The post-treatment comparison between the improved group and the invariant group was performed by unpaired t-test. Variation of the evaluation index over time was evaluated by repeated measures ANOVA. Multiple comparisons were corrected by the Bonferroni method. Results The EAT showed that parasympathetic activity was significantly suppressed in the improvement group, while the AS test showed significant fluctuations over time for the improvement and invariant groups. The interaction between the time course and the two factors in the improvement and invariant groups was not statistically evident. Although no significant difference was found, the improvement group showed a tendency to suppress parasympathetic activity and a tendency to stimulate sympathetic activity compared to the invariant group. Blood pressure in the improvement group showed a tendency to decrease. Conclusions EAT was found to suppress parasympathetic activity over time, and the AS test did not reveal an interaction effect of EAT on BR. However, there was a trend toward suppression of parasympathetic activity and stimulation of sympathetic activity in the improved group compared to the invariant group. Blood pressure in the improved group tended to decrease. It is possible that EAT may have a positive effect on autonomic neuropathy symptoms such as orthostatic dysregulation (OD), postural orthostatic tachycardia syndrome (POTS), etc. by stimulating the BRs. It is thought that the autonomic nervous system stimulating action and the immune system stimulating action act synergistically to express the therapeutic effect of EAT.

Autonomic Nervous System Regulation Effects of Epipharyngeal Abrasive Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Associated With Chronic Epipharyngitis.

To evaluate the autonomic nerve stimulation effect of epipharyngeal abrasive therapy (EAT) on myalgic encephalomyelitis/chronic fatigue syndrome (CFS) associated with chronic epipharyngitis. Heart rate variability analysis was performed. The study was conducted by analyzing heart rate variability. A total of 29 patients with chronic epipharyngitis who underwent EAT from July 2017 to April 2018 were classified into two groups: 11 patients in the CFS groupand 18 patients in the control group without CFS. The patients were classified as phase 1 during bed rest, phase 2 during nasal endoscopy, phase 3 during nasal abrasion, and phase 4 during oral abrasion. Electrocardiographic recordings were made, and autonomic function was compared and evaluated by measuring heart rate, coefficient of variation on R-R interval (CVRR), coefficient of component variance high frequency (ccvHF), and low frequency/ccvHF ratio (L/H) for each of the four phases.The Shapiro-Wilk test was performed to confirm the normality of the two groups, and the parametric test was selected. A repeated measures analysis of variance was performed to assess changes over time between the four events in the two groups. Multiple comparisons were corrected by the Bonferroni method. Comparisons between resting data and three events within each group were performed by paired t-test. The CFS group had an increased baseline heart rate compared to the control group, and the CFS group had a greater increase in parasympathetic activity and a decrease in heart rate with nasal abrasion. Oral abrasion elicited a pharyngeal reflex and increased heart rate and both sympathetic and parasympathetic activity. The CFS group was in a state of dysautonomia due to autonomic overstimulation, with an elevated baseline heart rate. The CFS group was considered to be in a state of impaired autonomic homeostasis, with an increased likelihood that overstimulation would induce a pathological vagal reflex and the Reilly phenomenon would develop. The direct effects of EAT on the autonomic nervous system were considered to be vagus nerve stimulation and the regulation of autonomic function by opposing stimulation input to sympathetic and parasympathetic nerves. As an indirect effect, bleeding from the epipharyngeal mucosa due to abrasion was thought to restore the function of the cerebral venous and lymphatic excretory systems and the autonomic nerve center.

Advancing autonomic nerve stimulation through computational models

Advancing autonomic nerve stimulation through computational models

The Impact of Mental Stress on Cardiovascular Health-Part II.

Endothelial dysfunction is one of the earliest manifestations of atherosclerosis, contributing to its development and progression. Mental stress induces endothelial dysfunction through increased activity of the sympathetic nervous system, release of corticotropin-releasing hormone from the hypothalamus, inhibition of nitric oxide (NO) synthesis by cortisol, and increased levels of pro-inflammatory cytokines. Mental-stress-induced increased output of the sympathetic nervous system and concomitant withdrawal of the parasympathetic inflammatory reflex results in systemic inflammation and activation of a neural–hematopoietic–arterial axis. This includes the brainstem and subcortical regions network, bone marrow activation, release of leukocytes into the circulation and their migration to the arterial wall and atherosclerotic plaques. Low-grade, sterile inflammation is involved in all steps of atherogenesis, from coronary plaque formation to destabilisation and rupture. Increased sympathetic tone may cause arterial smooth-muscle-cell proliferation, resulting in vascular hypertrophy, thus contributing to the development of hypertension. Emotional events also cause instability of cardiac repolarisation due to brain lateralised imbalance of cardiac autonomic nervous stimulation, which may lead to asymmetric repolarisation and arrhythmia. Acute emotional stress can also provoke severe catecholamine release, leading to direct myocyte injury due to calcium overload, known as myocytolysis, coronary microvascular vasoconstriction, and an increase in left ventricular afterload. These changes can trigger a heart failure syndrome mimicking acute myocardial infarction, characterised by transient left ventricular dysfunction and apical ballooning, known as stress (Takotsubo) cardiomyopathy. Women are more prone than men to develop mental-stress-induced myocardial ischemia (MSIMI), probably reflecting gender differences in brain activation patterns during mental stress. Although guidelines on CV prevention recognise psychosocial factors as risk modifiers to improve risk prediction and decision making, the evidence that their assessment and treatment will prevent CAD needs further evaluation.

Spontaneous Intrinsic Hepatic Vascular Oscillations

The liver is well known as a large blood reservoir that can shift both stressed and unstressed volumes passively and actively in response to changes in portal venous and hepatic arterial blood flow, inflow and outflow blood pressures, autonomic nervous stimulation, and various humoral and pathophysiological factors. Not described is the characteristic of the liver to intrinsically modulate its own vascular pressure and volume independent of extrinsic factors.METHODSMale Holtzman rats (n=5) were anesthetized (30 mg/kg sodium pentobarbital, i.p.) and heparinized (500 IU/kg, i.v.), the portal vein and inferior vena cava were isolated and cannulated, the liver was flushed with room temperature normal saline, and the liver quickly removed. Each liver was mounted on a scale in a 37°C chamber (95% O2‐5% CO2) and pump‐perfused (Masterflex) with donor rat blood at a baseline 1 ml/min/g of tissue. The hepatic venous pressure (Phv) was regulated by raising and lowering the blood reservoir. At each Time (see table), portal venous oscillations were counted over 3 to 12 min and the portal venous wavelet pulse pressures (Ppv) were measured over at least 40 wavelets.RESULTSThe portal venous pressures of 3 of the 5 livers oscillated spontaneously. One lasted only 26 min while the others went on for over 200 min. The characteristics of these oscillations varied widely from animal to animal, but there usually was an irregular cycle length and uneven wavelet magnitude that tended to degrade to a diminished size with higher frequency over time (see Figure 1). Rat Time (Min) Maneuver Mean Portal Venous Pulse Pressure (mmHg) Frequency (Wavelets/Min) Frequency (Hz) Cycle Length (Sec) 1 0 Baseline 2.1 ± 0.9 (SD) 8.08 0.135 7.42 95 Baseline 1.5 ± 0.8 16.10 0.268 3.73 107 Change Phv 2.5 ± 1.3 17.00 0.283 3.53 (0 to 10 mmHg) (P<0.001 vs. 95 Min Baseline) 180 Baseline 1.3 ± 0.5 18.67 0.311 3.21 2 0 Baseline 0.8 ± 0.4 14.42 0.240 4.16 60 Baseline 0.4 ± 0.3 20.00 0.333 3.00 130 Baseline 0.4 ± 0.2 23.78 0.396 2.52 3 0 Baseline 0.6 ± 0.3 8.67 0.144 6.92 CONCLUSIONSThis is a very limited data set, providing more questions than answers, but it opens a curiosity to much more investigation to understand the function of these intrinsic hepatic vascular oscillations under normal, reflex, and pathophysiological conditions.

Social Nervous Exercise Intervention and Its Association with Fasting Blood Glucose on Diabetes Mellitus Gestational

BACKGROUND: Gestational diabetes mellitus (GDM) has been identified as a major complication of pregnancies and has remained a major cause of perinatal morbidity and mortality, in both mother and child. Exercise can be used as a strategy to reduce hyperglycemia experienced during GDM. Regular exercise is important for a healthy pregnancy and can lower the risk of developing GDM. For women with GDM. Exercise is safe and can affect the pregnancy outcomes beneficially. The role of exercise about increases skeletal muscle glucose uptake and minimizing hyperglycemia. Social nervous (SaSo) exercise is a moderate-intensity exercise intervention that plays a role in controlling blood glucose through autonomic nervous stimulation so that it has an effect on glucose homeostasis. Social nervous exercise can stimulate the parasympathetic or myelinated vagus nerves. The social nerve or the social nervous system is the vagus nerve nc-X which is supported by cranial nerves, namely, nerves V, VII, IX, and XI centered in the nucleus ambiguous. AIM: The aim of the study is to determine the impact of a social nervous (SaSo) exercise training program consisting of warm-up, core (prayer movements), and cooling exercises on glucose homeostasis parameters in pregnant women diagnosed with GDM. METHODS: Thirty-seven pregnant women diagnosed with GDM at 24–28 weeks of gestation were allocated into two groups, thats the experimental group (n=19) with the SaSo program being regularly monitored and the control group (n=18) receiving only standard antenatal care for GDM. The Saso program started from the time diabetes was diagnosed until 6 weeks of intervention. Interventions were performed twice per week and sessions lasted 40–45 min. RESULTS: The baseline results for the experimental and control groups were homogeneous, without differences in the baseline variables (p > 0.05). Social nervous exercise the experimental group significantly reduced fasting blood glucose levels (p < 0.001) compared to the control group. CONCLUSIONS: A social nervous exercise program has a beneficial effect on fasting blood glucose levels in late pregnancy.

EFFECT OF HERBAL THERAPY STEEPING SALAM LEAF TO DECREASE IN BLOOD GLUCOSE LEVELS IN ELDERLY PATIENTS WITH DIABETES MELLITUS IN THE VILLAGE OF SUKODONO SUBDISTRICT OF SIDOARJO CITY

Introduction: Diabetes mellitus is a metabolic disease most often occurs in the elderly due to decreased function of the pancreas which produce insulin function. The number of elderly patients with DM in the village of Tell subdistrict of Sidoarjo regency Sukodono ignorance alternative ways to control blood sugar levels. The purpose of this study was to analyze the influence of herbal therapy steeping Salam leaves against a decrease in blood glucose levels in the elderly. Methods:This study design pre Experiment (One-group pre-post test design). Samples were taken using purposive sampling and obtained as many as 28 elderly Tell Rural District of Sukodono Sidoarjo. The independent variable is the herbal therapy steeping Salam leaves and the dependent variable is blood glucose levels in the elderly. Test Gluchose research instruments used for the measurement of blood sugar levels. Test data analysis using Paired T-test ? ? 0.05. Results:The results showed that the steeping Salam leaves for lowering blood glucose levels in elderly people with diabetes mellitus is evidenced by the results of Test Paired t-test showed ? = 0.000 before and after the treatment groups. Conclution:Seeing the results of this study can be concluded that the steeping Salam leaves containing astringent compounds can affect insulin sensitivity thereby stimulating the parasympathetic autonomic nerve stimulation and stimulate the release of insulin from the pancreas gland. Furthermore, the public are advised to be used as an alternative way to control blood sugar levels.

Human-relevant near-organ neuromodulation of the immune system via the splenic nerve

Neuromodulation of immune function by stimulating the autonomic connections to the spleen has been demonstrated in rodent models. Consequently, neuroimmune modulation has been proposed as a new therapeutic strategy for the treatment of inflammatory conditions. However, demonstration of the translation of these immunomodulatory mechanisms in anatomically and physiologically relevant models is still lacking. Additionally, translational models are required to identify stimulation parameters that can be transferred to clinical applications of bioelectronic medicines. Here, we performed neuroanatomical and functional comparison of the mouse, rat, pig, and human splenic nerve using in vivo and ex vivo preparations. The pig was identified as a more suitable model of the human splenic innervation. Using functional electrophysiology, we developed a clinically relevant marker of splenic nerve engagement through stimulation-dependent reversible reduction in local blood flow. Translation of immunomodulatory mechanisms were then assessed using pig splenocytes and two models of acute inflammation in anesthetized pigs. The pig splenic nerve was shown to locally release noradrenaline upon stimulation, which was able to modulate cytokine production by pig splenocytes. Splenic nerve stimulation was found to promote cardiovascular protection as well as cytokine modulation in a high- and a low-dose lipopolysaccharide model, respectively. Importantly, splenic nerve-induced cytokine modulation was reproduced by stimulating the efferent trunk of the cervical vagus nerve. This work demonstrates that immune responses can be modulated by stimulation of spleen-targeted autonomic nerves in translational species and identifies splenic nerve stimulation parameters and biomarkers that are directly applicable to humans due to anatomical and electrophysiological similarities.

Splenic Nerve Neuromodulation Reduces Inflammation and Promotes Resolution in Chronically Implanted Pigs.

Neuromodulation of the immune system has been proposed as a novel therapeutic strategy for the treatment of inflammatory conditions. We recently demonstrated that stimulation of near-organ autonomic nerves to the spleen can be harnessed to modulate the inflammatory response in an anesthetized pig model. The development of neuromodulation therapy for the clinic requires chronic efficacy and safety testing in a large animal model. This manuscript describes the effects of longitudinal conscious splenic nerve neuromodulation in chronically-implanted pigs. Firstly, clinically-relevant stimulation parameters were refined to efficiently activate the splenic nerve while reducing changes in cardiovascular parameters. Subsequently, pigs were implanted with a circumferential cuff electrode around the splenic neurovascular bundle connected to an implantable pulse generator, using a minimally-invasive laparoscopic procedure. Tolerability of stimulation was demonstrated in freely-behaving pigs using the refined stimulation parameters. Longitudinal stimulation significantly reduced circulating tumor necrosis factor alpha levels induced by systemic endotoxemia. This effect was accompanied by reduced peripheral monocytopenia as well as a lower systemic accumulation of CD16+CD14high pro-inflammatory monocytes. Further, lipid mediator profiling analysis demonstrated an increased concentration of specialized pro-resolving mediators in peripheral plasma of stimulated animals, with a concomitant reduction of pro-inflammatory eicosanoids including prostaglandins. Terminal electrophysiological and physiological measurements and histopathological assessment demonstrated integrity of the splenic nerves up to 70 days post implantation. These chronic translational experiments demonstrate that daily splenic nerve neuromodulation, via implanted electronics and clinically-relevant stimulation parameters, is well tolerated and is able to prime the immune system toward a less inflammatory, pro-resolving phenotype.

SPARC: Advanced Image‐Based Modelling of Neurostimulation in Support of Pre‐Clinical Investigations and Prototyping of Medical Devices

Smart engineering solutions to assist the design and optimization of miniaturized neural interfaces that provide targeted and selective stimulation of autonomic and peripheral nerves are critical for the advancement of bioelectronic medicine and for the optimization of neural prostheses. A major challenge is the identification of robust stimulation protocols despite the high variability of nerve anatomies between subject and species, which leads to considerable uncertainty in treatment doses and often to the failure of clinical trials and translational studies.Image‐based modelling of complex neurostimulation scenarios with hybrid electromagnetic and neuronal (EM‐neuronal) simulations and detailed implant models that feature neuroelectric models of nerves derived from medical/histological images, is a promising method to address this issue. We developed a computational pipeline in the simulation platform Sim4Life (ZMT Zurich MedTech AG, Switzerland) and as a dedicated service within the open‐source, web‐based O2SPARC platform developed by the IT’IS Foundation within the NIH SPARC Initiative. The pipeline allows semi‐automatic segmentation of nerve cross section images, fine‐grained tissue identification and generation of detailed 3D nerve models to accelerate the creation of complex neurostimulation nerve models. Major tissues, such as endoneurium, fat, connective tissue and epineurium, are identified by different computer vision approaches.Specifically, a number of tools have been developed to facilitate and automatize the meshing of labelled nerve segmentations, to extrude these meshes along nerve trajectories within computational human anatomical phantoms, and to enable the execution of EM simulations with new high performance low‐frequency unstructured EM solvers. These permit the modelling of tissues with spatially varying anisotropy (e.g., within the fascicles) as well as thin insulating layers such as the perineurium. Neuronal simulations are performed with parametrized electrophysiological models of myelinated sensory or motor axons, or unmyelinated axons. Stimulation thresholds can be automatically determined to predict recruitment curves and selectivity indices to optimize spatial selectivity of stimulation or the design of interfaces.To illustrate the benefits of our newly developed nerve segmentation pipeline for bioelectronic medicine, we provide examples of segmentation of multiple nerve cross‐sections from online databases. Pipeline performances and the different strategies are reported using a semantic (reliability of tissue segmentation) and a functional (reliability of prediction of stimulation thresholds) metric.The developed pipeline is ready to be used for different applications, such as the assessment of implant performances, the investigation of safety‐related issues (e.g. broken leads, acute vs chronic stimulation), and the planning of translational studies or the prediction of experimental outcomes.Support or Funding InformationNIH SPARC Initiative 1OT3OD025348‐01Example of developed pipeline, from a semi‐automatic segmentation of a nerve cross section to model prediction passing through 2D and 3D multidomain meshing and hybrid EM neuronal simulations.Figure 1

Cardiac Autonomic Nerves Stimulation Improves Hemodynamics and Clinical Status in Advanced Heart Failure Patients

Despite heart failure therapy advances, symptomatic congestion and low cardiac output in acute heart failure is a leading cause of mortality and morbidity. The purpose of this study was to investigate transvenous cardiac autonomic nerve stimulation (CANS) effects on in-hospital hemodynamics and clinical status. The study was a single-center, open label, clinical investigation of CANS. Twenty two subjects with LVEF <40% and at least two signs and symptoms of congestion were consented and enrolled. A purpose-built electrical stimulation catheter was placed in the left brachiocephalic vein via left subclavian vein access and connected to a purpose-built bedside neurostimulator used to deliver CANS therapy in-hospital for up to 96 hrs. The subjects had a mean baseline NT-proBNP of 10,518 pg/mL, LVEF of 25%, pulmonary capillary wedge pressure (PCWP) of 20 mmHg and presented with symptoms. CANS therapy was provided for a mean duration of 70 hrs. There were no device or study related adverse events reported. During CANS therapy mean cardiac index increased (1.8 to 2.0 L/min./m2), mean systemic vascular resistance decreased (24 to 20 WU), and mean PCWP decreased (20 to 14 mmHg) with stable MAP and HR. At discharge, mean edema pitting score improved 2 points, mean 6 minute hall walk distance (6MHW) increased 92 m and mean KCCQ-12 increased 12 points. At 30 day follow-up, edema pitting score improved 3 points, 6MHW increased 102 m and mean KCCQ-12 improved 38 points from baseline. Hemodynamic and clinical improvements occurred in the presence of stable medical management. Patients received at least 80 mg/day of furosemide, had minimal change to existing heart failure medical management, received no new IV vasoactive therapies, and a majority of the patients (17/22) received no furosemide dose uptitration during CANS Therapy. Alongside concomitant medical therapy, CANS holds promise as a tool to improve in-hospital hemodynamics and relieve congestion.

In vivo quantification of excitation and kilohertz frequency block of the rat vagus nerve

Objective. There is growing interest in treating diseases by electrical stimulation and block of peripheral autonomic nerves, but a paucity of studies on the excitation and block of small-diameter autonomic axons. We conducted in vivo quantification of the strength-duration properties, activity-dependent slowing (ADS), and responses to kilohertz frequency (KHF) signals for the rat vagus nerve (VN). Approach. We conducted acute in vivo experiments in urethane-anaesthetized rats. We placed two cuff electrodes on the left cervical VN and one cuff electrode on the anterior subdiaphragmatic VN. The rostral cervical cuff was used to deliver pulses to quantify recruitment and ADS. The caudal cervical cuff was used to deliver KHF signals. The subdiaphragmatic cuff was used to record compound action potentials (CAPs). Main results. We quantified the input–output recruitment and strength-duration curves. Fits to the data using standard strength-duration equations were qualitatively similar, but the resulting chronaxie and rheobase estimates varied substantially. We measured larger thresholds for the slowest fibres (0.5–1 m s−1), especially at shorter pulse widths. Using a novel cross-correlation CAP-based analysis, we measured ADS of ~2.3% after 3 min of 2 Hz stimulation, which is comparable to the ADS reported for sympathetic efferents in somatic nerves, but much smaller than the ADS in cutaneous nociceptors. We found greater ADS with higher stimulation frequency and non-monotonic changes in CV in select cases. We found monotonically increasing block thresholds across frequencies from 10 to 80 kHz for both fast and slow fibres. Further, following 25 s of KHF signal, neural conduction could require tens of seconds to recover. Significance. The quantification of mammalian autonomic nerve responses to conventional and KHF signals provides essential information for the development of peripheral nerve stimulation therapies and for understanding their mechanisms of action.

TCT-86 Cardiac Autonomic Nerve Stimulation Improves Hemodynamics and Clinical Status in Advanced Heart Failure Patients

Despite therapy advances in the management of heart failure (HF), symptomatic congestion and low cardiac output in acute HF are a leading cause of mortality and morbidity. The purpose of this study was to investigate transvenous cardiac autonomic nerve stimulation (CANS) effects on in-hospital

Cardiac Autonomic Nerves Stimulation Improves Hemodynamics and Clinical Status in Advanced Heart Failure Patients

Despite therapy advances in the management of heart failure, symptomatic congestion and low cardiac output in acute heart failure is a leading cause of mortality and morbidity. The purpose of this study was to investigate transvenous cardiac autonomic nerve stimulation (CANS) effects on in-hospital hemodynamics and signs and symptoms of congestion. The study was a single-center, observational, clinical investigation of CANS. Twelve subjects with left ventricular ejection fraction (LVEF)

Enhanced arrhythmogenic potential induced by renal autonomic nerve stimulation: Role of renal artery catheter ablation

Renal artery catheter ablation has been reported as a possible therapeutic option for drug-refractory ventricular arrhythmias (VAs) associated with structural heart diseases. To further clarify its therapeutic background, we examined the relationship between electrical nerve stimulation (ENS)-induced blood pressure (BP) elevation and occurrence of VAs by using an acute canine model of renal artery ablation. Using a decapolar electrode catheter, ENS was successively applied from the distal, mid, and proximal segments of the renal artery in 8 beagles. The same ENS was repeated after accomplishment of radiofrequency ablation at the ostial site of the renal artery by using an irrigation catheter. Before ablation, ENS increased BP from 140 ± 11/77 ± 11 to 167 ± 20/98 ± 16 mm Hg and heart rate from 100 ± 21 to 131±33 beats/min as well as induced VAs in 20 of the 45 ENS applications. Occurrence of VAs was associated with a greater magnitude of sympathetic nerve augmentation, and VAs were more frequently observed by ENS at the distal (67%) rather than mid/proximal segments of the renal artery (33%). Renal artery ablation was accomplished without any angiographic stenosis, and ENS-induced BP elevation, heart rate acceleration, and VAs occurrence were attenuated not only at the close segment (proximal) but also at the remote segments (mid/distal) of the renal artery. The renal autonomic nerves are considered as one of the therapeutic targets for suppression of frequent VAs because its activation has arrhythmogenic potential and induces premature ventricular beats.

Mechano-neuromodulation of autonomic pelvic nerve for underactive bladder: A triboelectric neurostimulator integrated with flexible neural clip interface

Mechano-neuromodulation of autonomic pelvic nerves was demonstrated for the first time using a triboelectric neurostimulator integrated with flexible neural clip interface. The detailed stimulation parameters such as current, pulse width, and charges generated by the proposed TENG were investigated for the stimulation of autonomic pelvic nerve. In in vivo experiments, different beats per minute (BPM) were delivered to the nerves to investigate the effect of stimulation frequency on mechano-neurostimulation while monitoring changes in bladder pressure and the occurrence of micturition. Furthermore, different numbers of pulses were applied to stimulate the pelvic nerve. The bladder contractions with micturition were observed when applying more than 50 BPM as well as one pulse. Comparison of stimulation was performed using a commercial stimulator with the similar long-pulse widths as generated by TENGs. In addition, chronic implantation of flexible clip interface was demonstrated with functionality test of the interface. The results demonstrate that this technology may potentially be used for self-powered mechano-neuromodulation for bladder function in the future.

Cardiac Autonomic Nerves Stimulation Improves Hemodynamics: A Pilot Study in Advanced Heart Failure Patients

Purpose Despite therapy advances in heart failure management, symptomatic congestion in acute heart failure is a leading cause of mortality and morbidity. An electrode catheter-based technology, cardiac autonomic nerve stimulation (CANS), is being investigated to transvenously stimulate cardiac autonomic nerves to control left-ventricular contractility and heart rate (HR). Methods The study was a single-center, clinical investigation to observe CANS effects on in-hospital hemodynamics and signs and symptoms of congestion. Five subjects with reduced left ventricular ejection fraction (LVEF Results Most subjects were male (3/5), had a mean age of 65 years, mean NT-proBNP of 3622 pg/mL and a mean Pulmonary Capillary Wedge Pressure (PCWP) of 30 mmHg. CANS was provided for a mean of 18 hours and was well tolerated. There were no adverse events reported. Mean LVEF increased in all subjects (27% to 35%) over the stimulation period. In three subjects, CANS directly modulated arterial pulse pressure (12% mean change) with a neutral HR effect ( Conclusion Alongside concomitant medical therapy, CANS directly improved hemodynamics and was associated with improved signs and symptoms of congestion. These improvements, and no adverse events, demonstrate that CANS holds promise as a tool to improve in-hospital hemodynamics and congestion. Future study is warranted to investigate CANS Therapy for longer stimulation duration, in expanded patient phenotypes, in more subjects.

Imaging fast neural traffic at fascicular level with electrical impedance tomography: proof of principle in rat sciatic nerve

Objective. Understanding the coding of neural activity in nerve fascicles is a high priority in computational neuroscience, electroceutical autonomic nerve stimulation and functional electrical stimulation for treatment of paraplegia. Unfortunately, it has been little studied as no technique has yet been available to permit imaging of neuronal depolarization within fascicles in peripheral nerve. Approach. We report a novel method for achieving this, using a flexible cylindrical multi-electrode cuff placed around nerve and the new medical imaging technique of fast neural electrical impedance tomography (EIT). In the rat sciatic nerve, it was possible to distinguish separate fascicles activated in response to direct electrical stimulation of the posterior tibial and common peroneal nerves. Main results. Reconstructed EIT images of fascicular activation corresponded with high spatial accuracy to the appropriate fascicles apparent in histology, as well as the inverse source analysis (ISA) of compound action potentials (CAP). With this method, a temporal resolution of 0.3 ms and spatial resolution of less than 100 µm was achieved. Significance. The method presented here is a potential solution for imaging activity within peripheral nerves with high spatial accuracy. It also provides a basis for imaging and selective neuromodulation to be incorporated in a single implantable non-penetrating peri-neural device.