Parasympathetic Nerve Stimulation Research Articles

A multiscale predictive digital twin for neurocardiac modulation.

Cardiac function is tightly regulated by the autonomic nervous system (ANS). Activation of the sympathetic nervous system increases cardiac output by increasing heart rate and stroke volume, while parasympathetic nerve stimulation instantly slows heart rate. Importantly, imbalance in autonomic control of the heart has been implicated in the development of arrhythmias and heart failure. Understanding of the mechanisms and effects of autonomic stimulation is a major challenge because synapses in different regions of the heart result in multiple changes to heart function. For example, nerve synapses on the sinoatrial node (SAN) impact pacemaking, while synapses on contractile cells alter contraction and arrhythmia vulnerability. Here, we present a multiscale neurocardiac modelling and simulator tool that predicts the effect of efferent stimulation of the sympathetic and parasympathetic branches of the ANS on the cardiac SAN and ventricular myocardium. The model includes a layered representation of the ANS and reproduces firing properties measured experimentally. Model parameters are derived from experiments and atomistic simulations. The model is a first prototype of a digital twin that is applied to make predictions across all system scales, from subcellular signalling to pacemaker frequency to tissue level responses. We predict conditions under which autonomic imbalance induces proarrhythmia and can be modified to prevent or inhibit arrhythmia. In summary, the multiscale model constitutes a predictive digital twin framework to test and guide high-throughput prediction of novel neuromodulatory therapy. KEY POINTS: A multi-layered model representation of the autonomic nervous system that includes sympathetic and parasympathetic branches, each with sparse random intralayer connectivity, synaptic dynamics and conductance based integrate-and-fire neurons generates firing patterns in close agreement with experiment. A key feature of the neurocardiac computational model is the connection between the autonomic nervous system and both pacemaker and contractile cells, where modification to pacemaker frequency drives initiation of electrical signals in the contractile cells. We utilized atomic-scale molecular dynamics simulations to predict the association and dissociation rates of noradrenaline with the β-adrenergic receptor. Multiscale predictions demonstrate how autonomic imbalance may increase proclivity to arrhythmias or be used to terminate arrhythmias. The model serves as a first step towards a digital twin for predicting neuromodulation to prevent or reduce disease.

1526-P: Cephalic Phase Insulin Release Requires Alpha Cells

The glucose-independent rise of insulin levels immediately at the start of a meal is known as the cephalic phase of insulin release and is a neurally mediated physiological reflex. We recently found that IL-1β mediates cephalic phase insulin secretion by modulating parasympathetic neuronal transmission. It has been established that pancreatic islets are richly innervated by the parasympathetic nervous system, yet the mechanism underlying neuronally mediated insulin release at basal glucose, as seen in cephalic phase, remain to be studied. Methods: We assessed the role of glucagon in cephalic phase insulin secretion using a transgenic mouse model in which alpha cells are selectively ablated. Further, we isolated pancreatic islets of wild-type mice, as well as alpha cell-ablated mice, and assessed insulin and glucagon secretion at low glucose after stimulation with IL-1β, a muscarinic agonist (carbachol) and both combined. Results: We observed that mice lacking glucagon-producing alpha cells fail to exhibit a cephalic phase insulin response. In vitro, we found that muscarinic activation stimulated glucagon secretion at basal glucose, but not insulin secretion. Co-stimulating islets with the muscarinic agonist and IL-1β stimulated insulin secretion at basal glucose, and strikingly this was not the case in alpha cell-ablated islets. Conclusion: Cephalic phase of insulin release mediated by IL-1β stimulation of parasympathetic nerves requires pancreatic alpha cells. This beta-cell response may be mediated by glucagon. Disclosure K.A.Trimigliozzi: None. S.J.Wiedemann: None. D.T.Meier: None. L.Rachid: None. H.Mereau: None. M.Böni-schnetzler: None. M.Y.Donath: Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk.

ID: 219000 Cross-Branch Effects of Parasympathetic Nerve Stimulation on Ileal Inflammation in Rats

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic idiopathic inflammatory disorder. While immunomodulators and biologics are available to induce and maintain remission, long-term efficacy is limited by the loss of response and serious side effects in more than 30% of patients. Vagal nerve stimulation has been reported to treat UC with promising results. On the other hand, sacral nerve stimulation (SNS) has been shown to exert anti-inflammation effects in rodent models of UC with an interesting spinal afferent and vagal efferent pathway. Accordingly, we hypothesized that SNS may also be able to modulate functions of organs that are innervated with vagus nerve but not sacral nerve. The aim of this study was to investigate possible anti-inflammatory effects of SNS on ileal inflammation in a rodent model of CD.

S1440 Novel Neuromodulation Treatment Using Repetitive Magnetic Stimulation for Diabetic Gastroparesis: Preliminary Results From a Proof-of-Concept Study

Introduction: Diabetic gastroparesis (DGp) is chartacterized by autonomic neuropathy, for which there are limited effective treatments. Stimulation of thoracic sympathetic and parasympathetic nerves may improve symptoms in patients with diabetic gastroparesis by enhancing gastric contractility. Our aim was to assess safety and feasibility of a novel, non-invasive treatment, Thoracic Splanchnic Magnetic Neuromodulation Therapy (ThorS-MagNT,) for refractory DGp in a proof-of-concept study. Methods: DGp patients, who required hospital admission and without known GI mucosal disease, were included. A mapping procedure in the left and right posterior mid-thoracic regions, using a single-pulse circular 90 mm coil (MAGSTIM, Whitland, UK) determined the location and minimum intensity required to achieve a motor evoked response (MEP) of 10 µV with 50% of trials (resting motor threshold) in the upper rectus abdominis and external oblique muscles. ThorS-MagNT was administered at 50% intensity above motor threshold, using a 70 mm double air film self-cooling coil (MAGSTIM Rapid2) positioned over bilateral pre-determined locations to deliver a total of 1200 stimulations at 1 Hz. Treatments were administered twice daily for five consecutive days. Safety and tolerability data were collected. ANMS GCSI-DD was assessed at baseline and throughout the treatment period. Patients who completed all ten treatments were defined as per protocol. Results: Seven DGp patients (6F; 1M) were enrolled . All subjects tolerated administered treatment sessions. One DGp patient experienced medication-related hypotension-a serious adverse event unrelated to study treatment. After resuscitation and missing one treatment, this subject completed 4 subsequent treatments. One patient reported self-limited tingling and numbness, which resolved after treatment. No other adverse events occurred. In four per protocol subjects, an average of 68.25% reduction in ANMS GCSI-DD score from baseline was observed (Table 1). Two other subjects had an average of 13.95% reduction in ANMS GCSI-DD and one study subject dropped out. Conclusion: ThorS-MagNT appears to be feasible, safe and a promising novel treatment for refractory DGp. Further studies are needed in larger samples to assess its effects on symptoms, hospitalization duration, gastric emptying and safety. Acknowledgement: Supported by the NIDDK Diabetic Complications Consortium grants DK076169 & DK115255.Table 1.: ANMS GCSI-DD scores at baseline versus during treatment.

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.

Combination of lipopolysaccharide and hypoxia-ischemia attenuates cholinergic anti-inflammatory effect in newborn rat brains

Aim: Pharmacologic parasympathetic nerve stimulation markedly reduces brain damage in a newborn rat model of hypoxia-ischemia (HI). Our aim is to determine whether a brain-protective effect can be achieved by parasympathetic nerve stimulation even with the synergy effect of lipopolysaccharide (LPS) and HI. Study design: 7-day-old Wistar rats were used. Rats received intraperitoneal administration of LPS which was followed by left carotid artery ligation. After a two-hour recovery period rats were placed in a hypoxic environment (8% oxygen) for 1 hour. Carbachol, used as an acetylcholine receptor agonist, or saline was injected subcutaneously immediately prior to one-hour hypoxia to determine its neuroprotective effect. Seven days later, the degree of brain damage in the ligated side of the hemisphere was compared to that in the contralateral hemisphere, which acts as reference. The relative difference in hemisphere area ((ligated side/non-ligated side) × 100%) was employed as an indicator of brain damage. Microglial aggregation (cells/mm 2) on the cortex and cytokine production in the ligated side of the hemisphere were also evaluated. Results: Three pups died in the carbachol group. There was no significant difference in brain damage between the saline (n = 34) and carbachol (n = 30) groups (86.0 ± 12.1% vs. 90.8 ± 13.6%, respectively). There was no significant difference in microglial aggregation between the saline and carbachol groups (155.7 ± 201.1 cells/mm2 vs. 89.8 ± 149.1 cells/mm2, respectively). IL-1β production in the saline and carbachol groups was 1.8 ± 1.2 pg/dL and 1.8 ± 1.1 pg/dL, respectively, with no significant difference between the groups. Conclusion: Combination of LPS and HI attenuates cholinergic anti-inflammatory effect in newborn rat brains.

Increased arrhythmia susceptibility in type 2 diabetic mice related to dysregulation of ventricular sympathetic innervation.

Patients with type 2 diabetes mellitus (T2DM) have a greater risk of developing life-threatening cardiac arrhythmias. Because the underlying mechanisms and potential influence of diabetic autonomic neuropathy are not well understood, we aimed to assess the relevance of a dysregulation in cardiac autonomic tone. Ventricular arrhythmia susceptibility was increased in Langendorff-perfused hearts isolated from mice with T2DM (db/db). Membrane properties and synaptic transmission were similar at cardiac postganglionic parasympathetic neurons from diabetic and control mice; however, a greater asynchronous neurotransmitter release was present at sympathetic postganglionic neurons from the stellate ganglia of db/db mice. Western blot analysis showed a reduction of tyrosine hydroxylase (TH) from the ventricles of db/db mice, which was confirmed with confocal imaging as a heterogeneous loss of TH-immunoreactivity from the left ventricular wall but not the apex. In vivo stimulation of cardiac parasympathetic (vagus) or cardiac sympathetic (stellate ganglion) nerves induced similar changes in heart rate in control and db/db mice, and the kinetics of pacing-induced Ca2+ transients (recorded from isolated cardiomyocytes) were similar in control and db/db cells. Antagonism of cardiac muscarinic receptors did not affect the frequency or severity of arrhythmias in db/db mice, but sympathetic blockade with propranolol completely inhibited arrhythmogenicity. Collectively, these findings suggest that the increased ventricular arrhythmia susceptibility of type 2 diabetic mouse hearts is due to dysregulation of the sympathetic ventricular control.NEW & NOTEWORTHY Patients with type 2 diabetes mellitus have greater risk of suffering from sudden cardiac death. We found that the increased ventricular arrhythmia susceptibility in type 2 diabetic mouse hearts is due to cardiac sympathetic dysfunction. Sympathetic dysregulation is indicated by an increased asynchronous release at stellate ganglia, a heterogeneous loss of tyrosine hydroxylase from the ventricular wall but not apex, and inhibition of ventricular arrhythmias in db/db mice after β-sympathetic blockade.

Genetic manipulation of autonomic nerve fiber innervation and activity and its effect on breast cancer progression.

The effects of autonomic innervation of tumors on tumor growth remain unclear. Here we developed a series of genetic techniques to manipulate autonomic innervation in a tumor- and fiber-type-specific manner in mice with human breast cancer xenografts and in rats with chemically induced breast tumors. Breast cancer growth and progression were accelerated following stimulation of sympathetic nerves in tumors, but were reduced following stimulation of parasympathetic nerves. Tumor-specific sympathetic denervation suppressed tumor growth and downregulated the expression of immune checkpoint molecules (programed death-1 (PD-1), programed death ligand-1 (PD-L1), and FOXP3) to a greater extent than with pharmacological α- or β-adrenergic receptor blockers. Genetically induced simulation of parasympathetic innervation of tumors decreased PD-1 and PD-L1 expression. In humans, a retrospective analysis of breast cancer specimens from 29 patients revealed that increased sympathetic and decreased parasympathetic nerve density in tumors were associated with poor clinical outcomes and correlated with higher expression of immune checkpoint molecules. These findings suggest that autonomic innervation of tumors regulates breast cancer progression.

Extracellular ATP and β-NAD alter electrical properties and cholinergic effects in the rat heart in age-specific manner.

Extracellular ATP and nicotinamide adenine dinucleotide (β-NAD) demonstrate properties of neurotransmitters and neuromodulators in peripheral and central nervous system. It has been shown previously that ATP and β-NAD affect cardiac functioning in adult mammals. Nevertheless, the modulation of cardiac activity by purine compounds in the early postnatal development is still not elucidated. Also, the potential influence of ATP and β-NAD on cholinergic neurotransmission in the heart has not been investigated previously. Age-dependence of electrophysiological effects produced by extracellular ATP and β-NAD was studied in the rat myocardium using sharp microelectrode technique. ATP and β-NAD could affect ventricular and supraventricular myocardium independent from autonomic influences. Both purines induced reduction of action potentials (APs) duration in tissue preparations of atrial, ventricular myocardium, and myocardial sleeves of pulmonary veins from early postnatal rats similarly to myocardium of adult animals. Both purine compounds demonstrated weak age-dependence of the effect. We have estimated the ability of ATP and β-NAD to alter cholinergic effects in the heart. Both purines suppressed inhibitory effects produced by stimulation of intracardiac parasympathetic nerve in right atria from adult animals, but not in preparations from neonates. Also, ATP and β-NAD suppressed rest and evoked release of acetylcholine (ACh) in adult animals. β-NAD suppressed effects of parasympathetic stimulation and ACh release stronger than ATP. In conclusion, ATP and β-NAD control the heart at the postsynaptic and presynaptic levels via affecting the cardiac myocytes APs and ACh release. Postsynaptic and presynaptic effects of purines may be antagonistic and the latter demonstrates age-dependence.

Modulation of Calcitonin, Parathyroid Hormone, and Thyroid Hormone Secretion by Electrical Stimulation of Sympathetic and Parasympathetic Nerves in Anesthetized Rats.

The thyroid and parathyroid glands are dually innervated by sympathetic (cervical sympathetic trunk [CST]) and parasympathetic (superior laryngeal nerve [SLN]) nerve fibers. We examined the effects of electrical stimulation of efferent or afferent nerve fibers innervating the thyroid and parathyroid glands on the secretion of immunoreactive calcitonin (iCT), parathyroid hormone (iPTH), 3,3′,5-triiodothyronine (iT3), and thyroxine (iT4) from the thyroid and parathyroid glands. In anesthetized and artificially ventilated rats, thyroid venous blood was collected. The rate of hormone secretion from the glands was calculated from plasma hormone levels, measured by ELISA, and the flow rate of thyroid venous plasma. SLNs or CSTs were stimulated bilaterally with rectangular pulses with a 0.5-ms width. To define the role of unmyelinated nerve fibers (typically efferent), the cut peripheral segments were stimulated at various frequencies (up to 40 Hz) with a supramaximal intensity to excite all nerve fibers. The secretion of iCT, iT3, and iT4 increased during SLN stimulation and decreased during CST stimulation. iPTH secretion increased during CST stimulation, but was not affected by SLN stimulation. To examine the effects of selective stimulation of myelinated nerve fibers (typically afferent) in the SLN, intact SLNs were stimulated with a subthreshold intensity for unmyelinated nerve fibers. iCT, iT3, and iT4 secretion increased during stimulation of intact SLNs at 40 Hz. These results suggest that excitation of myelinated afferents induced by low intensity and high frequency stimulation of intact SLNs promotes secretion of CT and thyroid hormones from the thyroid gland, potentially via reflex activation of parasympathetic efferent nerve fibers in the SLN.

Effect of distigmine on the contractile response of guinea pig urinary bladder to electrical field stimulation

Distigmine bromide (distigmine) is a reversible carbamate group cholinesterase (ChE) inhibitor. Although mainly used clinically for the treatment of myasthenia gravis, distigmine is also indicated for detrusor underactivity in Japan. According to the pharmacological classification of distigmine, its therapeutic effect against detrusor underactivity appears to be produced by enhanced urinary bladder smooth muscle (UBSM) contractility due to an increased concentration of acetylcholine between parasympathetic nerve endings and UBSM cells. However, ATP as well as acetylcholine is also released from parasympathetic nerve endings that dominate UBSM. The present study was thus carried out to investigate the potentiating effects of distigmine on the two UBSM contractile components in response to parasympathetic nerve stimulation induced by electrical field stimulation (EFS). In isolated guinea pig UBSM tissues, EFS (1–16Hz) produced tetrodotoxin-sensitive, frequency-dependent contractions. The contractile responses to EFS were largely diminished by atropine (10−6M), and the remaining contractile components in the presence of atropine were virtually abolished by α,β-methylene adenosine triphosphate (α,β-mATP) (10−4M). Distigmine (10−6M) significantly potentiated EFS-induced contractile components generated in the presence of α,β-mATP (10−4M), but did not potentiate EFS-induced contractile components generated in the presence of atropine (10−6M). These findings clearly indicate that distigmine strongly potentiates UBSM contraction selectively induced by parasympathetic nerve-derived acetylcholine, suggesting a potential mechanism by which distigmine restores detrusor underactivity.

미주신경 자극을 위한 새로운 방법 : 비침습적 TENS 적용에 대한 미주신경 자극의 치료적 효과

Purpose: The purpose of this study was to investigate the therapeutic effect of non-invasive vagus nerve stimulation by transcutaneous electrical nerve stimulation application on the autonomic nervous system of human body. Methods: Participants were seventeen healthy adults. Standard deviation of all normal N-N intervals(SDNN), root mean square of successive differences(RMSSD), low frequency(LF), high frequency(HF) were compared in pre and post Mean values after intervention. Data were analyzed in Wilcoxon's signed-ranks test. Results: The results of this study is that sistolic blood pressure and pulse rate decreased mean value after non-invasive vagus nerve stimulation by transcutaneous electrical nerve stimulation. High frequency, low frequency, SDNN, RMSSD increased mean value in heart rate variability after intervention. But that is not significant except for SDNN. Conclusion: Non-invasive vagus stimulation by transcutaneous electrical nerve stimulation effect on parasympathetic nerve stimulation, and then it might be effective method for autonomic nerve balance control.

Effects of Distigmine on Electrical Field Stimulation-Induced Contraction of Mouse Urinary Bladder Smooth Muscles

Distigmine bromide (distigmine), a reversible carbamate cholinesterase inhibitor, is used in Japan for treating detrusor underactivity, myasthenia gravis, and glaucoma. Although there is clinical evidence about the effectiveness of distigmine in the treatment of detrusor underactivity, mechanisms by which distigmine restores impaired urinary bladder smooth muscle (UBSM) contractility have not been fully investigated. The aims of this study were to investigate the potentiating effects of distigmine on UBSM contractions in response to parasympathetic nerve stimulation induced by electrical field stimulation (EFS) in mice. In isolated mouse UBSM, EFS (1-16 Hz) produced tetrodotoxin-sensitive, frequency-dependent contractions. The contractile responses to EFS were largely attenuated by atropine (10^-6 mol/l). UBSM contractility that occurred in the presence of atropine was nearly eliminated by the addition of α,β-methylene adenosine triphosphate (α,β-mATP, 10^-4 mol/l). Distigmine (3 × 10^-7 mol/l) significantly potentiated EFS-induced contractile responses engendered in the presence of α,β-mATP (10^-4 mol/l), but not atropine (10^-6 mol/l). These findings indicate that distigmine powerfully potentiates UBSM contractions selectively induced by parasympathetic nerve-derived acetylcholine, thereby demonstrating a potential mechanism by which it stimulates detrusor contractile function.

HW 01-4 CARDIOANKLE VASCULAR INDEX (CAVI) IN HYPERTENSION

Background: The cardio-ankle vascular index (CAVI) is a new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle, and was essentially derived from the stiffness parameterβtheory proposed by Hayashi. The conspicuous feature of CAVI is independency from blood pressure at the time of measurement. Aim: The purpose is to clarify the meaning of CAVI as a surrogate marker of arteriosclerosis, and also the role of CAVI in the blood pressure control system. Results: We reported that during a prospective study on 1000 patients for 7 years, a high CAVI was shown to be a predictive factor for cardiovascular events. Among antihypertensive drugs, we observed that Olmesartan (ARB) and Efonidipine (CCB) decreased CAVI, as well as decreasing blood pressure, indicating that those depressants would improve arterial stiffness. As for a regulatory factor of blood pressure, we observed that the CAVI value increased when blood pressure decreased during blood removal in the rabbits. And, CAVI value decreased, when blood pressure recovered by blood transfusion. Heart to ankle pulse wave velocity (hsPWV) was changed associating with blood pressure. During hypotensive attacks in patients taking hemodialysis therapy, some cases increased CAVI whereas other cases decreased CAVI. The former 's hypotension is associated with a reduction in cardiac output. The latter's hypotension was not associated with a reduction in cardiac output, but was associated with an increase in the high frequency of the coefficient of variation of R-R intervals (CVRR), indicating that parasympathetic nerve stimulation might decrease blood pressure by decreasing stiffness of the muscular arteries. In patients suffering from hypotension shock by sepsis, CAVI decreased, indicating that endotoxins might dilate the muscular arteries. Conclusion: CAVI was reflecting arterial stiffness, independently from blood pressure at mearing time, and might also reflect a part of vascular resistance. By measuring CAVI, the blood pressure control mechanism could be evaluated in several situations, as well as using it as a surrogate marker for arteriosclerosis.

Biophysical Processes in a Urinary Bladder Detrusor Smooth Muscle Cell during Rehabilitation Stimulation of Parasympathetic Efferents: a Simulation Study

In a computer model of an urinary bladder detrusor (UBD) smooth muscle cell (SMC), we investigated coupled changes in the membrane potential (MP), partial transmembrane currents, and intracellular calcium concentration ([Ca2 +]i), caused by parasympathetic stimulation. The respective data should help to determine the biophysical basis for the choice of parameters of medical rehabilitation electrical stimulation of the UBD. Ionotropic and metabotropic effects of such stimulation having different latency periods (LPs) were simulated by, respectively, an increase in the conductivity of purinoreceptor channels of the sarcolemma and a delayed (by 70 msec) increase in the permeability of calcium channels of the sarcoplasmic reticulum (store) sensitive to inositol triphosphate (IP3), the end-product of a chain of reactions triggered by activation of muscarinic cholinergic receptors. The modeled SMC responded to single stimulation by generation of action potential (AP) close in its parameters to those in the prototype. Application of long series of identical stimuli caused, after a transient interval, forced stationary oscillations of the MP and [Ca2 +]i. The magnitudes of the latter decreased, and the mean level increased with shortening of the interstimulus intervals (ISIs). It was found that the stimulation outcome needing prior experimental refining was determined by such parameters of the parasympathetic action as the durations of the purine and muscarinic components and the delay between these components. It has been shown that, during stimulation with ISIs shorter than the above-mentioned delay, the subsiquent stimulus activates P2X channels before expiration of the delay of the IP3-channel activation evoked by the preceding stimulus. This is actually equivalent to shortening of the interval between successive activations of P2X- and IP3-channels. Simple quantitative expressions were obtained for the parameters of stimulation; a given difference in the LPs of purine and muscarinic effects of parasympathetic stimulation allowed us to calculate the ISIs providing more efficient rehabilitation stimulation of the UBD parasympathetic nerves.

Effect of parasympathetic nerve stimulation on atrial and atrioventricular nodal electrophysiological characteristics

Effect of parasympathetic nerve stimulation on atrial and atrioventricular nodal electrophysiological characteristics

Effect of percutaneous pulsedmagnetic stimulation of the sacral nerve for the treatment of paraplegic patients with constipation

Objective To observe the effect of percutaneous pulsedmagnetic stimulation of the preganglionic parasympathetic nervous system of spinal at T 12-L1 vertebral level （2-4 sacral spinal cord）, in order to promote gastrointestinal peristalsis paraplegics and relieve symptoms of constipation .Methods Totals of 52 patients were divided into two groups by their admission date .The control group were applied the routine nursing care, including the psychology nursing care , drug intervention, diet, water balance, lower abdominal massage therapy, enema, pelvic floor muscle training and hyperbaric oxygen therapy .Based on the routine care, the intervention group was given the early percutaneous spinal cord pulsed magnetic stimulation of the preganglionic parasympathetic nerves of the spine at T 12 -L1 vertebral level （ 2 -4 sacral spinal cord ） . Results In the intervention group , 1 patient had cervical fracture and dislocation;2 patients had tumor invasion of the primary caudaequina of spinal cord.88.46%（23/26） patients had regular bowel movements.In the control group, only 61.54% （16/26） patients had regular bowel movements.The difference was statistically significant （χ2 =5.026,P〈0.05）.The effective rate of the intervention group was 76.9%（20/26）, which was significantly higher than 50.0% （13/26） in the control group （χ2 =4.046,P〈0.05）.Conclusions Percutaneous pulsed magnetic stimulation of the parasympathetic preganglionic nerve can improve the recovery of neurological function and provide a simple , noninvasive and painless method to reduce the constipation and improve patients ’ quality of life. Key words: Constipation; Paraplegia; Percutaneous pulsed magnetic stimulation

Hyperinsulinemia potentiates airway responsiveness to parasympathetic nerve stimulation in obese rats.

Obesity is a substantial risk factor for developing asthma, but the molecular mechanisms underlying this relationship are unclear. We tested the role of insulin in airway responsiveness to nerve stimulation using rats genetically prone or resistant to diet-induced obesity. Airway response to vagus nerve stimulation and airway M2 and M3 muscarinic receptor function were measured in obese-prone and -resistant rats with high or low circulating insulin. The effects of insulin on nerve-mediated human airway smooth muscle contraction and human M2 muscarinic receptor function were tested in vitro. Our data show that increased vagally mediated bronchoconstriction in obesity is associated with hyperinsulinemia and loss of inhibitory M2 muscarinic receptor function on parasympathetic nerves. Obesity did not induce airway inflammation or increase airway wall thickness. Smooth muscle contraction to acetylcholine was not increased, indicating that hyperresponsiveness is mediated at the level of airway nerves. Reducing serum insulin with streptozotocin protected neuronal M2 receptor function and prevented airway hyperresponsiveness to vagus nerve stimulation in obese rats. Replacing insulin restored dysfunction of neuronal M2 receptors and airway hyperresponsiveness to vagus nerve stimulation in streptozotocin-treated obese rats. Treatment with insulin caused loss of M2 receptor function, resulting in airway hyperresponsiveness to vagus nerve stimulation in obese-resistant rats, and inhibited human neuronal M2 receptor function in vitro. This study shows that it is not obesity per se but hyperinsulinemia accompanying obesity that potentiates vagally induced bronchoconstriction by inhibiting neuronal M2 muscarinic receptors and increasing acetylcholine release from airway parasympathetic nerves.

第19回カテコールアミンと循環器系研究会 洞調律と歩調取り部位に対する交感神経刺激,副交感神経刺激,および同時刺激の影響

第19回カテコールアミンと循環器系研究会 洞調律と歩調取り部位に対する交感神経刺激,副交感神経刺激,および同時刺激の影響

第13回 カテコールアミンと循環器系研究会 交感・副交感神経刺激による変時・変力作用に対するニューロペプタイドYの影響

第13回 カテコールアミンと循環器系研究会 交感・副交感神経刺激による変時・変力作用に対するニューロペプタイドYの影響