Gastric Motility Disorders Research Articles

Synchronized dual pulse gastric electrical stimulation improves gastric emptying and activates enteric glial cells via upregulation of GFAP and S100B with different courses of subdiaphragmatic vagotomy in rats.

Previous research and clinical practice have indicated that damage to the vagal nerve may seriously affect gastrointestinal physiological movement behavior. The aim of the current study was to observe the change of gastric motility, as well as enteric glial cells (EGCs) in the stomach with different courses of vagal nerve transection in rats prior to and following synchronized dual pulse gastric electrical stimulation. The gastric emptying rates were measured to assess the gastric motility. The glial markers, containing calcium binding protein (S100B) and glial fibrillary acidic protein (GFAP), were detected by reverse transcription‑quantitative polymerase chain reaction and double‑labeling immunofluorescence analysis. Ultrastructural changes of EGCs were observed using transmission electron microscopy. Gastric emptying was delayed in the terminal vagotomy group, compared with the terminal control group. The effect of long‑term synchronized dual pulse gastric electrical stimulation (SGES) was superior to short‑term SGES in terminal groups. The expression levels of S100B/GFAP were markedly decreased in the terminal vagotomy group compared with the terminal control group. Following short‑term or long‑term SGES, S100B/GFAP gene and protein expression increased in terminal groups. However, long‑term SGES was more effective than short‑term SGES and the difference was statistically significant. Vagal nerve damage leads to gastric motility disorder and weakens the function of EGCs. Therefore, SGES may improve stomach movement behavior and restore the impaired EGCs. The underlying mechanism of the effect remains elusive, but maybe associated with activation of EGCs.

Tu1678 - Prevalence of Gastric Motility Disorders in Patients with Functional Dyspepsia

Tu1678 - Prevalence of Gastric Motility Disorders in Patients with Functional Dyspepsia

Opposite effects of central oxytocin and arginine vasopressin on changes in gastric motor function induced by chronic stress

Hypothalamic oxytocin (OXT) and arginine vasopressin (AVP) are known to act oppositely on hypothalamic-pituitary-adrenal (HPA) axis, stress response and gastrointestinal (GI) motility. In rodents, exposure to restraint stress (RS) delays gastric emptying (GE), however, repeated exposure to the same stressor (chronic homotypic stress (CHS)), the delayed GE is restored to basal level, while hypothalamic OXT is upregulated. In contrast, when rats are exposed to chronic heterotypic stress (CHeS), these adaptive changes are not observed. Although the involvement of central OXT in gastric motor adaptation is partly investigated, the role of hypothalamic AVP in CHeS-induced maladaptive paradigm is poorly understood. Using in-vivo brain microdialysis in rats, the changes OXT and AVP release from hypothalamus were monitored under basal non-stressed (NS) conditions and in rats exposed to acute stress (AS), CHS and CHeS. To investigate the involvement of central endogenous OXT or AVP in CHS-induced habituation and CHeS-induced maladaptation, chronic central administration of selective OXT receptor antagonist L-371257 and selective AVP V1b receptor antagonist SSR-149415 was performed daily. OXT was measured higher in AS and CHS group, but not in CHeS-loaded rats, whereas AVP significantly increased in rats exposed to AS and CHeS. Additionally, the response of the hypothalamic OXT- and AVP-producing cells was amplified following CHS and CHeS, respectively. In rats exposed to AS for 90min solid GE significantly delayed. The delayed-GE was completely restored to the basal level following CHS, however, it remained delayed in CHeS-loaded rats. The CHS-induced restoration was prevented by L-371257, whereas SSR-149415 abolished the CHeS-induced impaired GE. A significant correlation was observed between GE and (i) OXT in CHS-loaded rats (rho=0.61, p<0.05, positively), (ii) AVP in CHeS-loaded rats (rho=0.69, p<0.05, negatively). Under long term stressed conditions, the release of AVP and OXT from hypothalamus may vary depending on the content of the stressors. Central AVP appears to act oppositely to OXT by mediating CHeS-induced gastric motor maladaptation. Long term central AVP antagonism might be a pharmacological approach for the treatment of stress-related gastric motility disorders.

A novel retractable laparoscopic device for mapping gastrointestinal slow wave propagation patterns.

Gastric slow waves regulate peristalsis, and gastric dysrhythmias have been implicated in functional motility disorders. To accurately define slow wave patterns, it is currently necessary to collect high-resolution serosal recordings during open surgery. We therefore developed a novel gastric slow wave mapping device for use during laparoscopic procedures. The device consists of a retractable catheter constructed of a flexible nitinol core coated with Pebax. Once deployed through a 5-mm laparoscopic port, the spiral head is revealed with 32 electrodes at 5mm intervals. Recordings were validated against a reference electrode array in pigs and tested in a human patient. Recordings from the device and a reference array in pigs were identical in frequency (2.6 cycles per minute; p=0.91), and activation patterns and velocities were consistent (8.9±0.2 vs 8.7±0.1mms-1; p=0.2). Device and reference amplitudes were comparable (1.3±0.1 vs 1.4±0.1mV; p=0.4), though the device signal-to-noise ratio was higher (17.5±0.6 vs 12.8±0.6dB; P<0.0001). In the human patient, corpus slow waves were recorded and mapped (frequency 2.7±0.03cycles per minute, amplitude 0.8±0.4mV, velocity 2.3±0.9mms-1). In conclusion, the novel laparoscopic device achieves high-quality serosal slow wave recordings. It can be used for laparoscopic diagnostic studies to document slow wave patterns in patients with gastric motility disorders.

Central Exogenous Neuropeptide‐S Ameliorates Stress‐induced Impaired Gastric Emptying through Orexin‐mediated Pathway in Rats

Stress is widely believed to play a major role in developing functional gastrointestinal (GI) disorders. Acute restraint stress (ARS) stimulates corticotrophin releasing factor (CRF) in the amygdala and paraventricular nucleus (PVN) of the hypothalamus which in turn plays a dominant role to delay gastric emptying (GE) via peripheral autonomic neural pathways in rats. Neuropeptide‐S (NPS), composed of 20 amino acids, is the endogenous ligand for the NPS receptor (NPSR) which is highly conserved in vertebrates including human. Within central nervous system (CNS), the NPS‐producing neurons are found mainly in locus coeruleus (LC) and amygdala which is involved in coping with fear and stress. Activation of the hypothalamus by stress is likely to be mediated in part by amygdala, the key limbic structure involved in the stress‐induced effects on the GI functions. Furthermore, CRF has been shown to excite NPS neurons in LC through the CRF‐1 receptor. In rodents, centrally administered NPS has been shown to inhibit anxiety, stress behaviors and stress‐stimulated fecal output in the rats. Orexin‐A (OXA), a hypothalamic neuropeptide, regulates feeding activity, energy homeostasis and arousal. Orexin receptor type‐1 (OXR1) is highly expressed in the dorsal vagal motor nucleus and OXA was shown to stimulate postprandial gastric motor functions via central vagal pathways. On the other hand, it has been shown that centrally administered NPS activates orexin‐containing neurons in hypothalamus in rats suggesting that OXA may contribute to the NPS‐mediated alterations in gastric motor functions under stressed conditions. To perform neuropeptide microdialysis, a microdialysis probe with large pore membrane was unilaterally placed into the central amygdala and LC. Central administrations of the drugs were performed through an injection cannula stereotaxically placed in the right lateral ventricle. NPS concentrations in microdialysates were assayed using EIA method. Solid GE was measured following an overnight fasting. Compared to their basal levels, ARS significantly reduced the NPS concentrations both in LC (5564.8 ± 186.8 ng/ml vs 562.9 ± 86.8 ng/ml, p&lt;0.01) and amygdala (5197.7 ± 217.1 ng/ml vs 91.8 ± 12.18 ng/ml, p&lt;0.01). In control rats, GE was 61.2 ± 3.4%. ARS significantly delayed gastric emptying 24.4 ± 3.2%; whereas, central administration of NPS (8 nmol, icv) completely restored the delayed GE induced by ARS (62.5 ± 5.7%, p&lt;0.01). Pretreatment of selective OXA antagonist SB‐334867 (40 μg, icv) significantly (p&lt;0.05) abolished the NPS‐induced restoration of delayed GE (38.9 ± 2.7%, p&lt;0.05). It is suggested that stress may alter NPS expression within CNS. Exogenous administration of NPS restores stress‐induced gastric dysmotility which was abolished by OXA antagonist, suggesting that the effect of NPS on stress‐induced gastric motility is partly OXA‐dependent. Central NPS may be a novel candidate for the treatment of stress‐induced gastric motility disorders.

Contraindications for video capsule endoscopy.

Video capsule endoscopy (VCE) has been applied in the last 15 years in an increasing field of applications. Although many contraindications have been put into perspective, some precautions still have to be considered. Known stenosis of the gastrointestinal tract is a clear contraindication for VCE unless surgery is already scheduled or at least has been considered as an optional treatment modality. In patients with a higher incidence of stenosis, as in an established diagnosis of Crohn’s disease, clinical signs of obstruction, prior radiation or surgical small bowel resection, a preceding test with the self-dissolving patency capsule can override this contraindication. Endoscopic placement of the capsule should be considered in patients with swallowing disorders to avoid aspiration. Esophageal or gastric motility disorders may require endoscopic capsule transport or application of prokinetics if the real-time viewer proofs delayed transit. In pregnant women, VCE should be restricted to urgent cases where diagnosis cannot be postponed after delivery, as data on safety are missing. There is theoretical and clinical evidence that patients with implanted cardiac devices such as a pacemaker, cardioverters or left heart assist devices, can safely undergo VCE in spite of still existing contraindication by manufacturers. Children from the age of 2 years have safely undergone VCE. Although video capsules are not proven safe with magnetic resonance imaging (MRI), first single cases of patients incidentally undergoing MRI with an incorporated capsule have been reported, showing susceptibility artifacts but no signs of clinical harm.

Pyloroplasty for Refractory Gastroparesis

Gastroparesis is a chronic gastric motility disorder in which the pathophysiology mimics a postvagotomy state. Pyloroplasty is beginning to emerge as a successful drainage procedure for refractory gastroparesis. Here we report our experience using pyloroplasty in the surgical management of diabetic and nondiabetic gastroparesis. A retrospective study was performed of 46 patients undergoing pyloroplasty for refractory gastroparesis from January 2010 through December 2013. Gastric emptying scintigraphy and the Gastroparesis Cardinal Symptom Index were assessed pre- and postoperatively. Laparoscopic pyloroplasty was performed in 42 patients, open pyloroplasty in three, and one patient was converted from laparoscopic to open pyloroplasty. Studies were repeated during the six to 12 month postoperative interval. The postoperative gastric emptying scintigraphy improved in 90 per cent of patients and normalized in 60 per cent. Postoperative T½ was significantly reduced (P = 0.001) as was four-hour retention (P < 0.001). The Gastroparesis Cardinal Symptom Index showed statistically significant reduction in symptom severity for all nine categories (P < 0.0005) as well as total symptom score (P < 0.005). No patients developed dumping syndrome. Pyloroplasty is a highly effective therapy for refractory gastroparesis, offering significant reduction in symptom severity, improvement in quality of life, and acceleration of gastric emptying.

A Multiscale Tridomain Model for Simulating Bioelectric Gastric Pacing.

Gastric motility disorders have been associated with abnormal slow wave electrical activity (gastric dysrhythmias). Gastric pacing is a potential therapy for gastric dysrhythmias; however, new pacing protocols are required that can effectively modulate motility patterns, while being power efficient. This study presents a novel comprehensive 3-D multiscale modeling framework of the human stomach, including anisotropic conduction, capable of evaluating pacing strategies. A high-resolution anatomically realistic mesh was generated from CT images taken from a human stomach. Principal conduction axes were calculated and embedded within this model based on a modified Laplace-Dirichlet rule-based algorithm. A continuum-based tridomain formulation was implemented and evaluated for performance and used to model the slow-wave propagation, which takes into account the two main cell types present in gastric musculature. Model parameters were found by matching predicted normal slow-wave activity to experimental observation and data. These simulation parameters were applied while modeling an external pacing event to entrain slow-wave patterns. The proposed formulation was found to be two times more efficient than a previous formulation for a normal slow-wave simulation. Convergence analysis showed that a mesh resolution of [Formula: see text] is required for an accurate solution process. The effect of different pacing frequencies on entrainment demonstrated that the pacing protocols are limited by the frequency of the native propagation and the refractory period of the cellular activity. The model is expected to become an important tool in studying pacing protocols for both efficiency and effectiveness.

OC-086 Gastric electrical stimulation (ges) for the treatment of refractory gastroparesis: a prospective 14-year experience in a uk centre

Introduction Gastroparesis is a debilitating disorder of gastric motility resulting in symptoms of nausea, vomiting, bloating and abdominal pain. In non-responders to medical treatment, Gastric Electrical Stimulation (GES) can improve symptoms leading to an improved quality of life. We present our 14-year experience with GES insertion in gastroparetic patients resistant to medical treatment. Method Data was prospectively collected from December 2000 to January 2015 in a local database. Information on patient demographics, pre and post GES insertion scores for nausea, vomiting, satiety, bloating and abdominal pain were collated. Factors such as aetiology of gastroparesis, comorbidities and feeding requirements were also recorded. Data on surgical intervention, complications and number of hospital admissions pre and post GES insertion were also included. Quality of life was assessed by SF-36 questionnaires. Results A total of 104 patients underwent GES insertion (Female 76, Male 28). The median length of stay was seven days (range 1–45 days) and follow up was 42.5 months (6–168 months). There were significant improvements in nausea severity score (p = Conclusion GES improves patient symptoms and quality of life. It reduces health care utilisation by avoiding long-term hospital stays and repeated admissions with a reduction in assisted feeding. The current study shows GES is a safe and an effective procedure in the treatment of refractory gastroparesis. To the best of our knowledge, our presented series is the longest consecutive study in Europe and UK alike. Disclosure of interest None Declared.

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability.

Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous on−off stimulation. Infection is the most serious implantation‐associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6 months and depends on surgical skill and experience. The most frequent stimulation‐associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non‐invasive VNS delivery systems do not require surgery and permit patient‐administered stimulation on demand. These non‐invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses.

CNP-pGC-cGMP-PDE3-cAMP Signal Pathway Upregulated in Gastric Smooth Muscle of Diabetic Rats.

Our previous studies have shown that CNP-NPR-B/pGC-cGMP is upregulated in the diabetic rats. The present study was designed to determine whether the upregulation of CNP-NPR-B/pGC-cGMP signal pathway affects cGMP-PDE3-cAMP signal pathway in diabetic gastric smooth muscle. The gastric smooth muscle motility was observed by using isometric measurement. PDEs expressions in diabetic gastric smooth muscle tissue were observed by using immunohistochemistry, Western blotting, and RT-PCR methods. The results demonstrated that the inhibitory effect of CNP on the spontaneous contraction of gastric antral circular smooth muscle was potentiated in STZ-induced diabetic rat. CNP-induced increase of cGMP and cAMP was much higher in diabetic gastric smooth muscle tissue than in controls. The expression of PDE3 is downregulated while the levels of gene expression of PDE1, PDE2, PDE4, and PDE5 were not altered in the diabetic gastric smooth muscle tissue. The results suggest that the sensitivity of gastric smooth muscle to CNP is potentiated via activation of CNP-pGC-cGMP-PDE3-cAMP signal pathway in STZ-induced diabetic rats, which may be associated with diabetes-induced gastric motility disorder.

Gastric Motility Disorders: A Possible Under-Diagnosed Cause of Non-responsive Non-ulcer Dyspepsia

Gastric Motility Disorders: A Possible Under-Diagnosed Cause of Non-responsive Non-ulcer Dyspepsia

MRI of the stomach: a pictorial review with a focus on oncological applications and gastric motility.

The purpose of this pictorial review is to demonstrate gastric pathology seen on magnetic resonance imaging (MRI) and discuss the essential MRI sequences for the evaluation of benign and malignant gastric pathologies. Common tumors of the stomach, polyposis syndromes, iatrogenic conditions, as well as other conditions of the stomach will be reviewed. The utility of MRI in the evaluation of patients with gastric malignancies and disorders of gastric motility will also be discussed.

Mo1306 Gastric Electrical Stimulation Improves Symptoms and Quality of Life At Up to 12 Years Follow-Up in Refractory Gastroparesis

Introduction: Gastroparesis is a debilitating disorder of gastric motility resulting in symptoms of nausea, vomiting, bloating and abdominal pain. In patients who are non-responders to medical treatment, Gastric Electrical Stimulation (GES) can improve symptoms, leading to an improved quality of life. We present our 12-year experience with GES insertion in gastroparetic patients resistant to medical treatment.

The role of the vagal pathway and gastric dopamine in the gastroparesis of rats after a 6‐hydroxydopamine microinjection in the substantia nigra

Gastroparesis is a common non-motor system symptom of Parkinson's disease (PD). However, the mechanism responsible for the gastric motor abnormality is not clear. We previously reported on the impaired gastric motility in 6-hydroxydopamine (6-OHDA) rats, which were treated with a bilateral microinjection of 6-OHDA in the substantia nigra (SN). We hypothesize that the enhanced dopamine system and reduced acetylcholine (Ach) in gastric tissues might contribute to the delayed gastric emptying observed in PD. A strain gauge force transducer, digital X-ray imaging system, Western blot, immunofluorescence and Radio Immunoassay were used in this study. Dopaminergic neurones in the SN were greatly reduced following the bilateral microinjection of 6-OHDA. 6-OHDA rats exhibited impaired gastric motility and delayed gastric emptying, accompanied by increased dopamine content and the overexpression of D2 receptors in the stomach. The administration of the D2 receptor antagonist domperidone relieved gastric dysmotility in 6-OHDA rats, but the D1 receptor antagonist SCH23390 failed to do so. Subdiaphragmatic vagotomy prevented the increase in the gastric dopamine content and D2 receptor expression and improved gastric dysmotility in 6-OHDA rats. Dopaminergic deficiency in the SN results in impaired gastric motility, possibly as a result of the enhanced activity of dopamine system and reduced Ach in gastric tissue. The vagus nerve plays an important role in peripheral gastric motility disorder.

Real-time gastric motility monitoring using transcutaneous intraluminal impedance measurements (TIIM)

The stomach plays a critical role in digestion, processing ingested food mechanically and breaking it up into particles, which can be effectively and efficiently processed by the intestines. When the motility of the stomach is compromised, digestion is adversely affected. This can lead to a variety of disorders. Current diagnostic techniques for gastric motility disorders are seriously lacking, and are based more on eliminating other possibilities rather than on specific tests. Presently, gastric motility can be assessed by monitoring gastric emptying, food transit, intragastric pressures, etc. The associated tests are usually stationary and of relatively short duration. The present study proposes a new method of measuring gastric motility, utilizing the attenuation of an oscillator-induced electrical signal across the gastric tissue, which is modulated by gastric contractions. The induced high-frequency oscillator signal is generated within the stomach, and is picked up transluminally by cutaneous electrodes positioned on the abdominal area connected to a custom-designed data acquisition instrument. The proposed method was implemented in two different designs: first a transoral catheter was modified to emit the signal inside the stomach; and second, a gastric retentive pill was designed to emit the signal. Both implementations were applied in vivo on two mongrel dogs (25.50 kg and 25.75 kg). Gastric contractions were registered and quantitatively compared to recordings from force transducers sutured onto the serosa of the stomach. Gastric motility indices were calculated for each minute, with transluminal impedance measurements and the measurements from the force transducers showing statistically significant (p < 0.05) Pearson correlation coefficients (0.65 ± 0.08 for the catheter-based design and 0.77 ± 0.03 for the gastric retentive pill design). These results show that transcutaneous intraluminal impedance measurement has the potential with further research and development to become a useful diagnostic technique.

La medicina integrativa en el manejo de la dispepsia funcional. Papel del preparado herbal STW 5

Functional dyspepsia is defined as a group of symptoms, whether related or unrelated to intake, localized in the upper abdomen, that manifest in the form of discomfort or epigastric pain, postprandial fullness and early satiety, in the absence of any demonstrable organic or structural anomaly. The etiopathogenesis and physiopathology of the process are unknown but factors that may be involved include gastric motility disorders, visceral hypersensitivity, psychological and genetic factors, Helicobacter pylori infection, and gastric acid hypersecretion. There is still no etiological treatment and consequently treatment is empirical and based on symptoms. This article reviews the main therapeutic options currently available, with special emphasis on the use of certain phytoceuticals (STW 5), in an attempt to integrate with traditional scientific medicine. This article also proposes an integrative therapeutic algorithm.

Reply from Kenton M. Sanders, Bhupal P. Bhetwal and Brian A. Perrino

Reply from Kenton M. Sanders, Bhupal P. Bhetwal and Brian A. Perrino

Effects and mechanisms of gastric electrical stimulation on visceral pain in a rodent model of gastric hyperalgesia secondary to chemically induced mucosal ulceration

Gastric electrical stimulation (GES) has been suggested as a potential treatment for patients with gastric motility disorders. The aim of this study was to examine the effects and mechanisms of GES on visceral pain in awaken rats. Under anesthesia, acetic acid was injected into the submucosal layer of the stomach wall in Sprague-Dawley (SD) male rats. Each rat was chronically placed with an intragastric balloon and two pairs of electrodes on gastric serosa for GES and at the neck muscles for electromyography (EMG) recordings respectively. The study was composed of four experiments. Exp 1 was designed to determine optimal GES parameters in reducing EMG response to gastric distention (GD). Exp 2 was performed to investigate the effect of GES on gastric tone/accommodation. Exp 3 was to investigate if the opioid pathway was involved in the analgesic effects of GES. Exp 4 was to assess the effectiveness of GES on the spinal cord neurons (T9-T10) responding to GD. (i) Gastric electrical stimulation with a train on of 0.1s and off of 0.4s, 0.25ms, 100Hz, and 6mA significantly reduced GD-induced EMG responses at GD 40, 60, and 80mmHg. (ii) The inhibitory effects of GES on the GD-induced EMG responses were blocked by Naloxone. (iii) GES inhibited 90% of high-threshold (HT) spinal neurons in response to GD. However, GES with the same parameters only suppressed 36.3% low-threshold (LT) neuronal response to GD. Gastric electrical stimulation with optimal parameters inhibits visceral pain; the analgesic effect of GES on visceral pain is mediated via the endogenous opioid system and the suppression of spinal afferent neuronal activities.

Breath Testing for Small Intestinal Bacterial Overgrowth: Maximizing Test Accuracy

The diagnosis of small intestinal bacterial overgrowth (SIBO) has increased considerably owing to a growing recognition of its association with common bowel symptoms including chronic diarrhea, bloating, abdominal distention, and the irritable bowel syndrome. Ideally, an accurate and objective diagnosis of SIBO should be established before initiating antibiotic treatment. Unfortunately, no perfect test exists for the diagnosis of SIBO. The current gold standard, small-bowel aspiration and quantitative culture, is limited by its high cost, invasive nature, lack of standardization, sampling error, and need for dedicated infrastructure. Although not without shortcomings, hydrogen breath testing provides the simplest noninvasive and widely available diagnostic modality for suspected SIBO. Carbohydrates such as lactulose and glucose are the most widely used substrates in hydrogen breath testing, with glucose arguably providing greater testing accuracy. Lactose, fructose, and sorbitol should not be used as substrates in the assessment of suspected SIBO. The measurement of methane in addition to hydrogen can increase the sensitivity of breath testing for SIBO. Diagnostic accuracy of hydrogen breath testing in SIBO can be maximized by careful patient selection for testing, proper test preparation, and standardization of test performance as well as test interpretation.