Gastric Slow Waves Research Articles

Transcutaneous Electrical Acustimulation Improves Gastrointestinal Disturbances Induced by Transcatheter Arterial Chemoembolization in Patients With Liver Cancers

Gastrointestinal (GI) disturbances occur in patients who receive chemotherapy via transcatheter arterial chemoembolization (TACE) and could last for an extended period of time in some cases. Antiemetic drugs have a potential risk of developing hepatic failure and are ineffective for delayed nausea and emesis. Transcutaneous electrical acustimulation (TEA) has recently been reported to exert antiemetic and prokinetic effects, but it is unknown whether it has an ameliorating effect on TACE-induced GI disturbances. This study was designed to evaluate effects and mechanisms of noninvasive TEA on GI symptoms in patients treated with TACE. Seventy-four patients with liver cancers (eighteen female; age 63.4 ± 1.1 years) scheduled for TACE were randomized to TEA (n = 37) or sham-TEA (n = 37). TEA was performed via acupoints, ST36 and PC6 using parameters previously optimized for GI motility (1 h, bid) from the postoperative day 0 (POD0) to POD2. Sham-TEA was performed using the same parameters via non-acupoints. Symptom questionnaires were completed daily. The electrogastrogram (EGG) and electrocardiogram (ECG) were recorded in the fasting state for 30 mins to assess gastric slow waves and autonomic functions, respectively, before and after the 3-day treatment. 1) In the acute phase (<24 h), TEA showed no effects on any of GI symptoms, compared with sham-TEA. 2) In the delayed phase (>24 h), TEA, compared with sham-TEA, decreased the percentage of patients who experienced nausea on POD3 (0% vs. 13.5%, p = 0.021), the nausea score on POD3 (p = 0.022), the anorexia score on POD2 (p = 0.040) and POD3 (p = 0.004), and the bloating score (POD1-3: p < 0.01). 3) In comparison with sham-TEA, TEA increased the number of spontaneous bowel movements (p = 0.001) and the Bristol score of the first stool (p = 0.014) and decreased the number of patients with the use of laxatives (p = 0.022). 4) Physiologically, the 3-day TEA but not sham-TEA increased the percentage of normal gastric slow waves (p < 0.001) and vagal activity (p = 0.006). The vagal activity was negatively correlated with the anorexia score (r = -0.267, p = 0.026). It was found that the sympathovagal ratio and tumor size>5 cm were independent risk factors predicting the occurrence of nausea in patients after TACE. TEA improves major TACE-induced GI disturbances in the delayed phase, including nausea, bloating, impaired gastric pace-making activity, and constipation in patients with liver cancers via the autonomic pathway.

The effect of chronic nausea on gastric slow wave spatiotemporal dynamics in children

Chronic nausea in adolescents with functional gastrointestinal disorders is an increasingly reported but poorly understood symptom that negatively affects quality of life. Functional gastrointestinal disorders are known to correlate closely with slow wave rhythm disturbances. The ability to characterize gastric electrophysiologic perturbations in functional nausea patients could provide potential diagnostic and therapeutic tools for nausea patients. We used high-resolution electrogastrograms (HR-EGG) to measure gastric slow wave parameters in pediatric chronic nausea patients and healthy subjects both pre- and postprandial. We computed the dominant frequency, percentage power distribution, gastric slow wave propagation direction, and speed from HR-EGG. We observed significant differences in the dominant frequency and power distributed in normal and bradyarrhythmia frequency ranges when comparing patients and healthy subjects. Propagation patterns in healthy subjects were predominantly anterograde, while patients exhibited a variety of abnormalities including retrograde, anterograde, and disrupted patterns. There was a significant difference in the preprandial mean slow wave direction between healthy subjects (222°±22°) and patients (103°±66°; p˂0.01), although the postprandial mean direction between healthy subjects and patients was similar (p=0.73). No significant difference in slow wave propagation speed was found between patients and healthy subjects in either pre- (p=0.21) or postprandial periods (p=0.75). The spatiotemporal characterization of gastric slow wave activity using HR-EGG distinguishes symptomatic chronic nausea patients from healthy subjects. This characterization may in turn inform and direct clinical decision-making and lead to further insight into its pathophysiology.

Detection of gastric slow oscillatory contraction using parasagittal cine MR images: Comparison with simultaneously measured electrogastrogram

PurposeTo determine if parasagittal gastric cine magnetic resonance imaging (MRI) is able to measure gastric oscillatory contractions around 0.05 Hz and to determine its relationship with electrical activity as measured by electrogastrography (EGG). MethodsAssessment of the gastric motility is important for the research of the enteric nervous system and for the diagnosis of functional gastric disorders. Electrogastrography is a non-invasive method that can measure gastric oscillatory electrical activity around 0.05 Hz (slow wave) using electrodes on the abdominal skin, but its sensitivity and specificity of the slow wave detection is limited. We used parasagittal gastric cine MRI around the angular incisure to measure gastric oscillatory contraction around 0.05 Hz in 24 healthy volunteers. Cine MRI was acquired with time resolution of 1 s for 10 min while freely breathing participants were lying on the bed. The gastric area of the cross section was measured for each MR image and assessed its change over time. The results were compared with those for simultaneously recorded EGG. ResultsThe main frequency of the gastric area change for each participant ranged from 0.041 to 0.059 Hz (mean ± S.D. = 0.049 ± 0.004), which corresponds to the gastric slow wave frequency (mean ± S.D. = 0.049 ± 0.004) as measured by EGG (p = 7.9585 × 10 −8, Kendall ‘s tau test). Cross correlation analysis showed that 22 of 24 participants’ gastric area changes were significantly (p < 0.05) related to the EGG waveforms. Displacement of the stomach due to respiration did not affect gastric area measurements. ConclusionsParasagittal cine MRI is correlated with EGG recordings and able to detect and quantifying gastric motility abnormalities.

Gastric slow wave rhythm identification using new approach based on noise-assisted multivariate empirical mode decomposition and Hilbert-Huang transform.

Electrogastrography (EGG) is the method of cutaneous recording of the myoelectrical activity of the stomach. A multi-channel signal is recorded non-invasively by means of electrodes placed outside the epigastric area. The normal electrical rhythm of the stomach (slow wave) may become significantly disturbed due to disorders of gastrointestinal tract. Abnormally fast electrical rhythms are termed tachygastria, while abnormally slow rhythms are known as bradygastria. Because some features of biological signals may go undetected using the classical methods of signal spectral analysis, we propose a new method for EGG rhythm identification. In this study, the calculation of the basic rhythms of multi-channel EGG signals is performed by means of the noise-assisted multivariate empirical mode decomposition (NA-MEMD) and Hilbert-Huang transform (HHT), using EGG data from eight healthy subjects. The results were compared with those obtained using classical spectral analysis. The mean values of the normogastric index for preprandial and two postprandial stages were found to be 64.78±11.37%, 61.29±15.86%, and 63.80±13.24%, respectively. The obtained values of normogastric index are consistent with the normal human physiological value, which is approximately 70% for healthy subjects. This method is able to capture features of the signal which are mostly undetectable by standard EGG processing methods. The EGG dominant rhythm identification using the instantaneous normogastric, bradygastric, and tachygastric indices provides new insights into biological EGG patterns.

Effects and Mechanisms of Transcutaneous Electrical Acustimulation on Postoperative Recovery After Elective Cesarean Section

To explore the effects and mechanisms of transcutaneous electrical acustimulation (TEA) on postoperative recovery after cesarean section (CS). A total of 108 women who underwent CS were randomized to receive TEA or sham-TEA. Four hours after CS, electrogastrogram (EGG) and electrocardiogram (ECG) were recorded for 30 min to assess gastric slow waves and autonomic functions, respectively. TEA at ST36 or sham-TEA at non-acupoints was performed for one hour right after recording ECG and EGG and then twice daily from postoperative days (POD) 1 to 3. In the morning of POD4, the EGG and ECG were recorded again for 30 min. TEA enhanced postoperative recovery associated with lower GI motility, reflected as a reduction in time of first flatus (p = 0.002) and time of first defecation (p < 0.001), an increase in the Bristol stool score (p < 0.001) and the number of SBMs (p < 0.001) in comparison with sham-TEA. TEA reduced symptoms associated with upper GI motility, including a reduction in time to resume semifluid (p = 0.008), and the total score of loss of appetite (p = 0.003) and belching (p = 0.038) from POD1 to POD3. Physiologically, TEA but not sham-TEA increased the percentage of normal gastric slow waves on POD4 compared with POD0 (p = 0.001). TEA reduced the visual analogue scale (VAS) pain score from POD1 to POD3 (p < 0.001). TEA but not sham-TEA increased vagal activity (p = 0.013) and decreased sympathetic activity (p = 0.013) on POD4 compared with POD0. Two factors were found to be independent predictors of shortened time of the first defecation: the use of TEA and a shorter surgical duration. Needleless non-invasive TEA at ST36 is effective in promoting both lower and upper GI symptoms after CS by enhancing vagal and suppressing sympathetic activities [Correction added on 23 June 2020, after first online publication: The first word of the preceded sentence has been corrected.].

Wireless Real-Time Electrogastrography Monitoring System

Gastrointestinal (GI) diseases are one of the rising issues in medical field from the past two decades. The incidence and prevalence rates have shown a notable rise in these conditions, thereby leading to an increase in morbidity and mortality rate. The principle aim of this study is to design and develop a system that can acquire signals precisely and non-invasively from the abdominal skin over the stomach and share the obtained results to the patient mobile wirelessly. This technique enables the user to monitor their gastric condition effortlessly. This standalone system, for detecting various abdominal disorders incorporates the technique of Electrogastrography (i.e.,) recording gastric signals non-invasively using surface electrodes. The proposed real-time gastric recording and monitoring system is designed using Laboratory Virtual Instrument Engineering Workbench (LabVIEW) software in addition to the initial analog circuitries. The entire system is enclosed in an elastic belt to make it wearable for different abdominal torsos. The real-time data acquired is shared with the patient mobile using National Instruments (NI) Data dashboard application mobile application. On the other hand, the data recorded from the system is analyzed in Matrix Laboratory (MATLAB) using moving average algorithm to obtain precise electrogastrographic envelopes. The gastric signal recording is obtained from ten healthy individuals by following the developed experimental protocol in postprandial session. The data obtained is used in evaluating and quantifying the gastric slow wave propagation in the individuals by extracting the signal features in temporal and frequency domains. The obtained results prove the efficiency of the proposed design, with the fixed electrode position making the system user-friendly.

Robust Methods to Detect Abnormal Initiation in the Gastric Slow Wave from Cutaneous Recordings.

Upper gastrointestinal (GI) disorders are highly prevalent, with gastroparesis (GP) and functional dyspepsia (FD) affecting 3% and 10% of the US population, respectively. Despite overlapping symptoms, differing etiologies of GP and FD have distinct optimal treatments, thus making their management a challenge. One such cause, that of gastric slow wave abnormalities, affects the electromechanical coordination of pacemaker cells and smooth muscle cells in propelling food through the GI tract. Abnormalities in gastric slow wave initiation location and propagation patterns can be treated with novel pacing technologies but are challenging to identify with traditional spectral analyses from cutaneous recordings due to their occurrence at the normal slow wave frequency. This work advances our previous work in developing a 3D convolutional neural network to process multi-electrode cutaneous recordings and successfully classify, in silico, normal versus abnormal slow wave location and propagation patterns. Here, we use transfer learning to build a method that is robust to heterogeneity in both the location of the abnormal initiation on the stomach surface as well as the recording start times with respect to slow wave cycles. We find that by starting with training lowest-complexity models and building complexity in training sets, transfer learning one model to the next, the final network exhibits, on average, 80% classification accuracy in all but the most challenging spatial abnormality location, and below 5% Type-I error probabilities across all locations.

Simulation-based Analysis of Magnetogastrography Sensor Configurations for Characterizing Gastric Slow Wave Dysrhythmias.

The routine diagnosis of gastric motility disorders represents a significant problem to current clinical practice. Magnetogastrography (MGG) provides a non-invasive option for assessing gastric slow wave (SW) dysrhythmias that are associated with motility disorders. However, its ability to characterize SW propagation is impaired by the limited spatial coverage of existing superconducting quantum interference devices (SQUIDs). Recently developed optically-pumped magnetometers can potentially substitute SQUIDs and enable subject-specific MGG arrays with greater spatial coverage. This study developed simulations of gastric MGG to determine the distribution of the magnetic fields (MFs) generated by SWs above the torso, and investigated the impact of several realistic dysrhythmic patterns of propagation. The distribution of MFs was found to vary significantly for different patterns of SW propagation, with ectopic dysrhythmia displaying the greatest difference from normal. Notably, some important proportion of the MFs lay outside the coverage of an existing experimental SQUID array used in gastrointestinal research for some simulated SW propagation patterns, such as retrograde activity. Results suggest that MGG measurements should be made over the entire frontal face of the torso to capture all of the strongest MFs generated by SWs.Clinical relevance- This provides a guide for the placement of MGG sensors for the capture of both normal and dysrhythmic gastric slow wave propagation.

Minimally Invasive Gastric Electrical Stimulation Using a Newly Developed Wireless Gastrostimulator: A Pilot Animal Study.

Background/AimsGastric electrical stimulation (GES) is a feasible modality for the treatment of gastroparesis; however, the presently available device requires invasive surgical implantation for long-term stimulation and repeated surgical procedure after a period of time. This study is aimed at developing a wireless miniature GES device and testing its endoscopic insertion in animal models.MethodsEndoscopic gastric implantation of the GES device was performed on 5 healthy weaner pigs under general anesthesia. We created an endoscopic submucosal pocket and inserted the gastro-electrical stimulator. In vivo gastric slow waves were recorded and measured during electrical stimulation. A multi-channel recorder, called an electrogastrogram, was used to record the gastric myoelectrical activity in the study.ResultsThe gastric slow waves on the electrogastrogram were more consistent with GES on the gastric tissues compared to no stimulation. The frequency-to-amplitude ratio was also significantly altered after the electrical stimulation.ConclusionsGES is feasible with our minimally invasive wireless device. This technique has the potential to increase utilization of GES as a treatment alternative.

Effects of electroacupuncture on stress-induced gastric dysrhythmia and mechanisms involving autonomic and central nervous systems in functional dyspepsia.

Electroacupuncture (EA) is widely used as an effective method to treat stress-related disorders. However, its mechanisms remain largely unknown. The aim of this study was to investigate the effects and mechanisms of EA on gastric slow wave (GSW) dysrhythmia and c-Fos expression in the nucleus of the solitary tract (NTS) induced by stress in a rodent model of functional dyspepsia (FD). Rats in the neonatal stage were treated using intragastric iodoacetamide. Eight weeks later, the rats were implanted with electrodes in the stomach for the measurement of GSW and electrodes into accupoints ST36 for EA. Autonomic functions were assessed by spectral analysis of heart rate variability. Rats were placed for 30 min in a cylindrical plastic tube for acute restraint stress. The involvement of a central afferent pathway was assessed by measuring c-Fos-immunoreactive cells in the NTS. 1) EA normalized restraint stress-induced impairment of GSW in FD rats. 2) EA significantly increased vagal activity (P = 0.002) and improved sympathovagal balance (P = 0.004) under stress in FD rats. 3) In FD rats under restraint stress, plasma norepinephrine concentration was increased substantially (P < 0.01), which was suppressed with EA. 4) The EA group showed increased c-Fos-positive cell counts in the NTS compared with the sham EA group (P < 0.05) in FD rats. Acute restraint stress induces gastric dysrhythmia in a rodent model of FD. EA at ST36 improves GSW under stress in FD rats mediated via the central and autonomic pathways, involving the NTS and vagal efferent pathway.

The effects of low-and high-frequency non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) on gastric slow waves evaluated using in vivo high-resolution mapping in porcine.

Gastric motility is regulated by an electrophysiological activity called slow-wave and neuronal innervations by the vagus nerve. Transcutaneous auricular vagal nerve stimulation (taVNS) has been demonstrated to have therapeutic potential for a wide range of medical conditions, including the management of gastric dysfunctions. The main objective of this study was to gain a better understanding of how non-invasive neuromodulation influences gastric slow wave under in vivo conditions. TaVNS protocols were applied in conjunction with 192-channel gastric bioelectrical mapping in porcine subjects under general anesthesia. The spatiotemporal profiles of gastric slow wave were assessed under two different taVNS protocols at 10 and 80Hz. The taVNS protocols effectively altered the interval and amplitude of gastric slow waves, but not the velocity or the percentage of spatial dysrhythmias. In the subjects that responded to the protocols, the 10Hz protocol was shown to normalize slow-wave propagation pattern in 90% of the subjects, whereas the 80Hz protocol was shown to inhibit slow waves in 60% of the subjects. Chronic responses of gastric motility and slow waves in response to taVNS should be investigated using non-invasive means in conscious subjects in future.

Non‐invasive Targeted Gastric Vagal Complex Stimulation: Preliminary in Human Cutaneous Measures of Gastric Slow Wave Function

Gastric slow wave abnormalities have been associated with upper gastrointestinal motility disorders. Invasive studies in humans have described normal and abnormal propagation of the gastric slow wave, and recent non‐invasive studies have shown that multi‐electrode cutaneous measures of gastric slow wave function correlate with symptom severity in patients with gastroparesis and functional dyspepsia (Gharibans et al, Clinical Gastroenterology and Hepatology, 2019). Invasive Neurostimulation of gastric Vagal complexes are thought to result in satiety (Abiliti, Transcend), anti‐nausea (Entera) and general weight loss (vBLOC), but effects of invasive neuromodulation on gastric motility are not clear. Our group developed: 1) a wearable non‐invasive electrogastrography (EGG) device that reliably records gastric slow wave function and 2) a new non‐invasive targeted gastric Vagus nerve stimulation (ntG‐VNS) system. The challenge is to further develop a combined ntG‐VNS/EGG system that may be used as a tool to probe Gastric disease states, and eventually diagnose and or treat gastric motility disorders.MethodsA 10 lead ambulatory high resolution electrogastrogram (AHR‐EGG) system for ambulatory use (Gharibans et al, Scientific Reports, 2018) was used to record gastric myolectric activity cutaneously (Fig 1A). The gastric proximal fundus was visualized at a depth of 2cm using a Butterfly high frequency transducer at 1–5MHz (Fig 1b) and guided stimulator electrode placement. After fundus localization ntG‐VNS was applied inferior to the lower sternum with 2 (0.5 inch) disk electrodes 0.5 inch apart in rostral caudal orientation (Fig 1A) utilizing short pulsed intermittent stimulation for 14 minutes during simultaneous EGG. Cutaneous recordings were sampled at 250Hz, filtered below 0.15Hz and down‐sampled to 1Hz. Artifact rejection methods as described in (Gharibans et al, Scientific Reports, 2018) were next applied, followed by median filtering of the 0.05Hz power derived from spectrograms across all electrodes to derive EGG power. Baseline activity was derived from percentiles of power across the recording, and was subtracted to derive normalized EGG power to be used for subsequent analysis.ResultsEGG power prior to nTG‐VNS showed a center frequency of .0493 Hz (Fig 2A). Post nTG‐VNS EGG showed highly significant reduction of slow wave power (Fig 2B), below the baseline pre‐stimulation levels.ConclusionntG‐VNS immediately abolishes gastric slow wave propagation as measured by non‐invasive AHR‐EGG over a 14 min time period. Taken together, targeted non‐invasive gastric vagus nerve stimulation technology may prove to be a valuable human research tool, focused on improving our fundamental understanding of gastric motility vagal reflexes.Support or Funding InformationThis work was in part supported by the U.S. Department of Health and Human Services, Biological Advanced Research and Development Authority, BARDA: (75A50119C00038)Figure 1Figure 2

SPARC: Simultaneous Assessment of Gastric Emptying and Motility with Contrast Enhanced Magnetic Resonance Imaging in Humans

PurposeMagnetic resonance imaging (MRI) of the gastrointestinal (GI) tract is an emerging technique for non‐invasive assessment of gastric emptying and motility in animals and humans. However, addition of MRI contrast agents to the test meal is often required to produce high luminal contrast to facilitate image analysis. Here, we reported a recipe of a test meal that is all natural (e.g. gadolinium‐free) and safe for humans. The ingredients of the test meal all contain relatively high concentration of manganese, which allow the lumen of the GI tract to be visible inside MRI. To capture gastric emptying and motility simultaneously, we have developed a dynamic 3D imaging protocol with high spatial and temporal resolution and an image segmentation and analysis algorithm.MethodSix healthy volunteers (3 woman; age 24–31) participated in this study. All subjects were asked to fast for 12 hours. Subjects were scanned using a 3T Siemens Prisma MRI scanner using an 18‐channel body coil and a 32‐channel spine coil. Prior to meal consumption, pre‐prandial gastric volume was quantified using a 3D true fast imaging (TRUFI) with steady‐state free precession sequence under free breathing. Then the subjects were instructed to ingest 350 ml of a semi‐solid test meal (263kcal) that contains blended natural foods (i.e. pineapple, banana, blueberry, firm tofu) with a relatively high concentration of manganese. Post‐meal MRI scans were performed using a 3D Spoiled Gradient Echo Variant (VIBE) sequence under gentle breaths over a 90‐minute time course. Post‐prandial gastric volumes, as well as antral contraction frequency and amplitude of the peristaltic wave, were quantified from the dynamic 3D MRI images using a custom‐built image processing pipeline.ResultsPre‐prandial gastric volume was measured prior to test meal consumption (30.98±12.29 mL). After the subjects consumed the test meal, the presence of manganese in the meal enhanced the contrast of the gastric lumen (Fig. 1). The imaging protocol collected fast real‐time MRI scans of the stomach processing and emptying of a meal and the algorithms quantified gastric motility and emptying rate. The stomach volume decreased at a rate of 1.58±0.50 mL/min, mainly attributed to volume decrease in the fundus and the corpus (1.31±0.53 mL/min) than in the antrum (0.28±0.15 mL/min). The frequency of gastric contractions was 2.79±0.17 cycles/min, which was in line with the frequency of gastric slow wave in humans. The displacement of the luminal wall (i.e. contraction amplitude) was greater at the antrum (7.42±1.39 mm) than at the fundus and the corpus (4.52±0.25 mm), as illustrated in Fig. 2.ConclusionHere, we developed a contrast‐enhanced gastric MRI protocol to non‐invasively monitor gastric emptying and motility in humans. Such experimental protocol was further empowered by advanced image analysis to enable comprehensive assessment of gastric functions and physiology. In summary, the proposed method may become a reliable standard to guide diagnosis and treatment of gastric disorders in humans.Support or Funding InformationNIH SPARC OT2OD023847Example gastric MRI images of the stomach distended with the test meal. The contrast of the gastric lumen was significantly enhanced due to the presence of manganese in the meal.Figure 1Mapping amplitude of gastric contractions on the luminal wall. The displacement of the luminal wall was greatest at the antrum, followed by the corpus, and smallest at the fundus.Figure 2

Ameliorating effects of sacral neuromodulation on gastric and small intestinal dysmotility mediated via a sacral afferent-vagal efferent pathway.

In a recent study of sacral nerve stimulation (SNS) for colonic inflammation, a possible spinal-vagal pathway was implicated. The aim of this study was to provide evidence for such a pathway by investigating the effects of SNS on dysmotility of the stomach and duodenum that are not directly innervated by the sacral efferents. Twenty-seven rats were chronically implanted with wire electrodes for SNS and gastrointestinal slow waves. SNS was performed in several acute sessions to investigate its effects on gastric/duodenal slow waves and emptying/transit impaired by glucagon and rectal distention (RD). (a) SNS increased the percentage of normal gastric slow waves impaired by glucagon (from 53.9% to 77.0%, P<.0001) and RD (from 64% to 78%, P=.037). This improvement was abolished by atropine. (b) Similar effects were observed with SNS on duodenal slow waves, which was also blocked by atropine. (c) SNS normalized delayed gastric emptying induced by glucagon (control: 61.3%, glucagon: 44.3%, glucagon+SNS: 65.8%) and RD (control: 61.3%, RD: 46.7%, RD+SNS: 64.3%). It also normalized small intestinal transit delayed by RD (P=.001, RD+SNS vs RD; P=.9, RD+SNS vs control). (4) Both glucagon and RD induced an increase in the sympathovagal ratio (P=.007, glucagon vs baseline; P<.001, RD vs baseline) and SNS decreased the ratio (P=.006, glucagon+SNS vs glucagon; P=.04, RD+SNS vs RD). Neuromodulation of the sacral nerve improves gastric and small intestinal pacemaking activity and transit impaired by glucagon and RD by normalizing the sympathovagal balance via a retrograde neural pathway from the sacral nerve to vagal efferents.

The brain‐penetrating, orally bioavailable, ghrelin receptor agonist HM01 ameliorates motion‐induced emesis in Suncus murinus (house musk shrew)

HM01, a novel, orally bioavailable, brain-penetrating agonist of ghrelin receptors, ameliorates emesis in Suncus murinus. This study compared HM01's activity against motion sickness with that of the less brain-penetrating ghrelin receptor agonist, HM02. The potential of HM01 and HM02 to relax isolated mesenteric arteries and to increase feeding was investigated. Radio telemetry was used to record gastric slow waves and body temperature. Plethysmography was used to measure respiratory function. HM01 and HM02 were administered p.o. 1 hr prior to provocative motion, and c-Fos expression in brain sections was assessed. HM01 and HM02 both relaxed precontracted arteries, yielding EC50 values of 2.5 ± 0.5 and 3.5 ± 0.4 nM respectively. HM01 increased feeding, but HM02 did not. Both compounds caused hypothermia and bradygastria. Motion induced 123 ± 24 emetic events. HM01, but not HM02, reduced motion-induced emesis by 67.6%. Motion increased c-Fos expression in the nucleus tractus solitarius (NTS), dorsal motor nucleus of the vagus (DMNV), medial vestibular nucleus (MVe), central nucleus of the amygdala, and paraventricular hypothalamic nucleus (PVH). HM01 alone increased c-Fos expression in the area postrema, NTS, DMNV, PVH, and arcuate hypothalamic nucleus; HM02 had a similar pattern except it did not increase c-Fos in the PVH. Both compounds antagonized the motion-induced increases in c-Fos expression in the MVe. HM01 is more effective than HM02 in preventing motion-induced emesis. The difference in potency may relate to activation of ghrelin receptors in the PVH.

The pharmacokinetic parameters and the effect of a single and repeated doses of memantine on gastric myoelectric activity in experimental pigs.

BackgroundMemantine, currently available for the treatment of Alzheimer's disease, is an uncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors. Under normal physiologic conditions, these unstimulated receptor ion channels are blocked by magnesium ions, which are displaced after agonist-induced depolarization. In humans, memantine administration is associated with different gastrointestinal dysmotility side effects (vomiting, diarrhoea, constipation, motor-mediated abdominal pain), thus limiting its clinical use. Mechanism of these motility disorders has not been clarified yet. Pigs can be used in various preclinical experiments due to their relatively very similar gastrointestinal functions compared to humans. The aim of this study was to evaluate the impact of a single and repeated doses of memantine on porcine gastric myoelectric activity evaluated by means of electrogastrography (EGG).MethodsSix adult female experimental pigs (Sus scrofa f. domestica, mean weight 41.7±5.0 kg) entered the study for two times. The first EGG was recorded after a single intragastric dose of memantine (20 mg). In the second part, EGG was accomplished after 7-day intragastric administration (20 mg per day). All EGG recordings were performed under general anaesthesia. Basal (15 minutes) and study recordings (120 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Running spectral analysis based on Fourier transform was used. Results were expressed as dominant frequency of gastric slow waves (DF) and power analysis (areas of amplitudes).ResultsSingle dose of memantine significantly increased DF, from basic values (1.65±1.05 cycles per min.) to 2.86 cpm after 30 min. (p = 0.008), lasting till 75 min. (p = 0.014). Basal power (median 452; inter-quartile range 280–1312 μV^2) raised after 15 min. (median 827; IQR 224–2769; p = 0.386; NS), lasting next 30 min. Repetitively administrated memantine caused important gastric arrhythmia. Basal DF after single and repeated administration was not different, however, a DF increase in the second part was more prominent (up to 3.18±2.16 after 15 and 30 min., p<0.001). In comparison with a single dose, basal power was significantly higher after repetitively administrated memantine (median 3940; IQR 695–15023 μV^2; p<0.001). Next dose of 20 mg memantine in the second part induced a prominent drop of power after 15 min. (median 541; IQR 328–2280 μV^2; p<0.001), lasting till 120 min. (p<0.001).ConclusionsBoth single and repeated doses of memantine increased DF. Severe gastric arrhythmia and long-lasting low power after repeated administration might explain possible gastric dysmotility side effects in the chronic use of memantine.

System and Methodology to Study and Stimulate Gastric Electrical Activity in Small Freely Behaving Animals

Aim: To develop and validate a system that can wirelessly acquire gastric slow waves and deliver electrical pulses to the stomach. Materials &amp; methods: The system is composed of a front-end and a back-end unit connected to a computer, which runs a custom-made graphical user interface. The system was validated on benchtop and in vivo studies. Results: Benchtop validation showed an appropriate frequency response to acquire slow waves. Moreover, the system was able to deliver electrical pulses at amplitudes up to ±10 mA. Slow wave activity recorded from the stomach of rats was in the range of approximately five cycles per minute (cpm). Pulses delivered to the stomach of a rat every 15 s and reduced the activity to 4 cpm during the stimulation period. Conclusion: This study reports the first wireless system and methodology that can be used to acquire slow waves and deliver electrical stimulation to the stomach of small freely behaving animals.

Gastric Slow Wave and Autonomic Nervous Function in Cirrhotic Patients With Esophageal Varices After Ligation-A Clinical Research

Gastric Slow Wave and Autonomic Nervous Function in Cirrhotic Patients With Esophageal Varices After Ligation-A Clinical Research

Bayesian inverse methods for spatiotemporal characterization of gastric electrical activity from cutaneous multi-electrode recordings.

Gastrointestinal (GI) problems give rise to 10 percent of initial patient visits to their physician. Although blockages and infections are easy to diagnose, more than half of GI disorders involve abnormal functioning of the GI tract, where diagnosis entails subjective symptom-based questionnaires or objective but invasive, intermittent procedures in specialized centers. Although common procedures capture motor aspects of gastric function, which do not correlate with symptoms or treatment response, recent findings with invasive electrical recordings show that spatiotemporal patterns of the gastric slow wave are associated with diagnosis, symptoms, and treatment response. We here consider developing non-invasive approaches to extract this information. Using CT scans from human subjects, we simulate normative and disordered gastric surface electrical activity along with associated abdominal activity. We employ Bayesian inference to solve the ill-posed inverse problem of estimating gastric surface activity from cutaneous recordings. We utilize a prior distribution on the spatiotemporal activity pertaining to sparsity in the number of wavefronts on the stomach surface, and smooth evolution of these wavefronts across time. We implement an efficient procedure to construct the Bayes optimal estimate and demonstrate its superiority compared to other commonly used inverse methods, for both normal and disordered gastric activity. Region-specific wave direction information is calculated and consistent with the simulated normative and disordered cases. We apply these methods to cutaneous multi-electrode recordings of two human subjects with the same clinical description of motor function, but different diagnosis of underlying cause. Our method finds statistically significant wave propagation in all stomach regions for both subjects, anterograde activity throughout for the subject with diabetic gastroparesis, and retrograde activity in some regions for the subject with idiopathic gastroparesis. These findings provide a further step towards towards non-invasive phenotyping of gastric function and indicate the long-term potential for enabling population health opportunities with objective GI assessment.

490 High-Resolution Electrogastrogram Identifies Disturbed Gastric Slow Waves and Dysautonomia in Subjects With Dumping Syndrome

INTRODUCTION: Rapid gastric emptying is the sine qua non of Dumping Syndrome (DS), which can arise from multiple etiologies including gastric surgery and diabetes mellitus. The relationship between DS and gastric myoelectric activity is unknown, but dysautonomia may play a role. We sought to characterize features of gastric slow waves and autonomic indices among subjects with DS using the ambulatory high-resolution electrogastrogram (HR-EGG). METHODS: Eleven subjects completed 24-hour ambulatory HR-EGG. Fasting abdominal computed tomography scan was utilized for stomach localization and placement of the ambulatory HR-EGG array, consisting of 10 skin mounted electrodes. Subjects were divided into two groups: DS (4F, age 53.2 ± 9.3, BMI 31.7 ± 11, 79-93% gastric emptying at 1 hour on scintigraphy, two diabetics, one prior gastric surgery, one gastrointestinal amyloidosis) and healthy age-matched controls (4M/3F, age 47.6 ± 28, BMI 24.5 ± 3.7). All subjects completed the PAGI-SYM foregut symptom questionnaire and a diary capturing all meals and sleep/wake times. RESULTS: Subjects with DS had significantly higher mean PAGI-SYM foregut symptom severity scores (1.9 ± 1.0 vs 0.1 ± 0.1; P = 0.0007). HR-EGG showed that DS subjects had a significantly lower slow wave speed (4.6 vs 5.9 ± 0.4; P = 0.0003) and higher post-prandial power change (11 vs 3.5 ± 3.6; P = 0.002) compared to healthy controls. The global percent stomach activity throughout the 24-hour ambulatory recordings was not different between groups. DS subjects trended towards higher post-prandial area under the curve EGG activity at both the 1-hour (261.9 ± 360.7 vs 172.9 ± 137.5) and 4-hour marks (1108.8 ± 1589.4 vs 656.3 ± 442.2). In addition, subjects with DS had significantly lower heart rate variability than controls: RMSDD (39.9 ± 9.7 vs 58.1 ± 7.8) and SDNN (12.6 ± 4.2 vs 23.7 ± 3.2); no differences were noted in mean heart rate (Table 1). CONCLUSION: Ambulatory HR-EGG clearly identifies that there are spatial abnormalities of the gastric slow wave present among subjects with DS. Moreover, reduced heart rate variability - a marker of autonomic dysfunction - was observed among subjects with DS. These findings suggest that gastric dysrhythmias and autonomic disturbances should be given important consideration in the pathogenesis of Dumping Syndrome.