Functional Motility Disorders Research Articles

High-energy pacing inhibits slow-wave dysrhythmias in the small intestine.

The motility of the gastrointestinal tract is coordinated in part by rhythmic slow waves, and disrupted slow-wave patterns are linked to functional motility disorders. At present, there are no treatment strategies that primarily target slow-wave activity. This study assessed the use of pacing to suppress glucagon-induced slow-wave dysrhythmias in the small intestine. Slow waves in the jejunum were mapped in vivo using a high-resolution surface-contact electrode array in pigs (n = 7). Glucagon was intravenously administered to induce hyperglycemia. Slow-wave propagation patterns were categorized into antegrade, retrograde, collision, pacemaker, and uncoupled activity. Slow-wave characteristics such as period, amplitude, and speed were also quantified. Postglucagon infusion, pacing was applied at 4 mA and 8 mA and the resulting slow waves were quantified spatiotemporally. Antegrade propagation was dominant throughout all stages with a prevalence of 55 ± 38% at baseline. However, glucagon infusion resulted in a substantial and significant increase in uncoupled slow waves from 10 ± 8% to 30 ± 12% (P = 0.004) without significantly altering the prevalence of other slow-wave patterns. Slow-wave frequency, amplitude, and speed remained unchanged. Pacing, particularly at 8 mA, significantly suppressed dysrhythmic slow-wave patterns and achieved more effective spatial entrainment (85%) compared with 4 mA (46%, P = 0.039). This study defined the effect of glucagon on jejunal slow waves and identified uncoupling as a key dysrhythmia signature. Pacing effectively entrained rhythmic activity and suppressed dysrhythmias, highlighting the potential of pacing for gastrointestinal disorders associated with slow-wave abnormalities.NEW & NOTEWORTHY Glucagon was infused in pigs to induce hyperglycemia and the resulting slow-wave response in the intact jejunum was defined in high resolution for the first time. Subsequently, with pacing, the glucagon-induced dysrhythmias were suppressed and spatially entrained for the first time with a success rate of 85%. The ability to suppress slow-wave dysrhythmias through pacing is promising in treating motility disorders that are associated with intestinal dysrhythmias.

Optimization of Gastric Pacing Parameters Using High-Resolution Mapping.

Abnormal slow-wave activity has been associated with functional motility disorders. Gastric pacing has been investigated to correct slow-wave abnormalities, but clinical therapies are yet to be established. This study aimed to define optimal parameters to advance the application of gastric pacing. High-resolution gastric mapping was utilized to evaluate four pacing parameters in in-vivo pig studies: (i) orientation of the pacing electrodes (longitudinal vs circumferential), (ii) pacing energy (900 vs 10,000 ms mA2), (iii) the pacing location (corpus vs antrum), and (iv) pacing period (between 12 and 36 s). The probability of slow-wave initiation and entrainment with the pacing electrodes oriented longitudinally was significantly higher than with electrodes orientated circumferentially (86 vs 10%). High-energy pacing accelerated entrainment over the entire mapped field compared to low-energy pacing (3.1±1.5 vs 7.3±2.4 impulses, p < 0.001). Regardless of the location of the pacing site, the new site of slow-wave initiation was always located 4-12 mm away from the pacing site, between the greater curvature and negative pacing electrode. A pacing period between 14-30 s resulted in stable slow-wave initiation and entrainment. These data will now inform effective application of gastric pacing in future studies, including human translation.

Ultrasonographic assessment of effect of neostigmine on abomasal atony in young calves

Present communication was focused on the ultrasonographic evaluation of the prokinetic effect of neostigmine in buffalo calves with abomasal atony. Six buffalo calves were selected for the study with absence of rumination, loss of feed intake, mild distended abdomen, achezia and frequent history of laying down and getting up with reduced rumen motility. Abomasal atony was confirmed by the ultrasonographic assessment of the abomasum motility. Calves were administered with injection neostigmine 0.02 mg/kg body weight slow intravenously along with 500 ml of 0.9% normal saline under the ultrasonographic monitoring. Abomasal motility was initiated by 18 to 42 minutes and complete abomasal motility was noticed by 150 to 180 minutes after administration of medications. Clinical improvement was noticed on the third day of therapy and efficacy of the neostigmine was noticed by ultrasonography. Present study concludes that neostigmine has prokinetic effect in buffalo calves with abomasal functional motility disorders. Ultrasonography is the best tool for assessment of abomasal motility without any adverse reactions and complications.

Spatial response of jejunal pacing defined by a novel high-resolution multielectrode array.

Gastric pacing has shown preclinical success in modulating bioelectrical slow-wave activity and has potential as a novel therapy for functional motility disorders. However, the translation of pacing techniques to the small intestine remains preliminary. This paper presents the first high-resolution framework for simultaneous pacing and response mapping of the small intestine. A novel surface-contact electrode array, capable of simultaneous pacing and high-resolution mapping of the pacing response, was developed and applied in vivo on the proximal jejunum of pigs. Pacing parameters including the input energy and pacing electrode orientation were systematically evaluated, and the efficacy of pacing was determined by analyzing spatiotemporal characteristics of entrained slow waves. Histological analysis was conducted to determine if the pacing resulted in tissue damage. A total of 54 studies were conducted on 11 pigs, and pacemaker propagation patterns were successfully achieved at both low (2 mA, 50 ms) and high (4 mA, 100 ms) energy levels with the pacing electrodes oriented in the antegrade, retrograde, and circumferential directions. The high energy level performed significantly better (P = 0.014) in achieving spatial entrainment. Comparable success (greater than 70%) was achieved when pacing in the circumferential and antegrade pacing directions, and no tissue damage was observed at the pacing sites. This study defined the spatial response of small intestine pacing in vivo revealing effective pacing parameters for slow-wave entrainment in the jejunum. Intestinal pacing now awaits translation to restore disordered slow-wave activity associated with motility disorders.NEW & NOTEWORTHY A novel surface-contact electrode array customized for the small intestine anatomy enabled simultaneous pacing and high-resolution response mapping. The spatial response of small intestine bioelectrical activity to pacing was mapped for the first time in vivo. Antegrade and circumferential pacing achieved spatial entrainment over 70% of the time and their induced pattern was held for 4-6 cycles postpacing at high energy (4 mA, 100 ms, at ∼2.7 s which corresponds to 1.1 × intrinsic frequency).

Chronic abdominal pain after bariatric surgery: a narrative review

Objective: This paper reviews the prevalence, etiology, risk factors, diagnosis and prevention of chronic abdominal pain after bariatric surgery. Introduction: Chronic pain is a very common and complex problem that has serious consequences on individuals and society. It frequently presents as a result of a disease or an injury. Obesity and obesity-related comorbidities are a major health problem and are dramatically increasing year after year. Dieting and physical exercise show disappointing results in the treatment of obesity. Therefore, bariatric surgery is increasingly widely offered as a weight reducing strategy. In our pain clinic we see a lot of patients who suffer from chronic abdominal pain after bariatric surgery. This review aims to explore the link between chronic abdominal pain and bariatric surgery in this specific type of patients. Method: The review is based on searches in PubMed, Embase and Cochrane databases. Keywords are used in different combinations. We did a cross-reference of the articles included. Results: Chronic abdominal pain after bariatric surgery is very common. Around 30% of the bariatric patients experience persistent abdominal pain. An explanation for the abdominal pain is found in 2/3 of these patients. There is a wide variety of causes including behavioral and nutritional disorders, functional motility disorders, biliary disorders, marginal ulceration and internal hernia. Another, frequently overlooked, cause is abdominal wall pain. Unexplained abdominal pain after bariatric surgery is present in 1/3 of the patients with persistent abdominal pain. More studies are needed on the risk factors and prevention of unexplained abdominal pain in bariatric patients.

Characterizing Spatial Signatures of Gastric Electrical Activity Using Biomagnetic Source Localization

The motility patterns in the gastrointestinal tract are regulated, in part, by bioelectrical events known as slow waves (SWs). Understanding temporal and spatial features of gastric SWs can help reveal the underlying causes of functional motility disorders. This study investigated the ability of source localization techniques to characterize the spatial signatures of SW activity using simulated and experimental magnetogastrography data. Two SW propagation patterns (antegrade and retrograde) with two rhythms (normogastric and bradygastric) were used to simulate magnetic fields using 4 anatomically realistic stomach and torso geometries. Source localization was performed utilizing the equivalent current dipole (ECD) and the equivalent magnetic dipole (EMD) models. In the normogastric simulations when compared with the SW activity, the EMD model was capable of identifying the SW propagation in the lateral, antero-posterior, and supero-inferior axes with the median correlation coefficients of 0.66, 0.53, and 0.83, respectively, whereas the ECD model produced lower correlation scores (median: 0.52, 0.44, and 0.44). Moreover, the EMD model resulted in distinct and opposite spatial signatures for the antegrade and retrograde propagation. Similarly, when experimental data was used, the EMD model revealed antegrade-like signatures where the propagation was mostly towards the third quadrant in the supero-inferior (preprandial: 49%, postprandial: 35%) and antero-posterior (preprandial: 49%, postprandial: 50%) axes. The EMD model was able to identify and classify the spatial signatures of SW activities, which can help to inform the interpretation of non-invasive recordings of gastric SWs as a biomarker of functional motility disorders.

A generalized framework for pacing artifact removal using a Hampel filter.

Cardiac pacing is a clinical therapy widely used for treating irregular heart rhythms. Equivalent techniques for the treatment of gastric functional motility disorders hold great potential. Accurate analysis of pacing studies is often hindered by the stimulus artifacts which are superimposed on the recorded signals. This paper presents a semi-automated artifact detection method using a Hampel filter accompanied by 2 separate artifact reconstruction methods: (i) an auto-regressive model, and (ii) weighted mean to estimate the underlying signal. The developed framework was validated on synthetic and experimental signals containing large periodic pacing artifacts alongside evoked bioelectrical events. The performance of the proposed algorithms was quantified for gastric and cardiac pacing data collected in vivo. A lower mean RMS difference was achieved by the artifact segment reconstructed using the auto-regression ([Formula: see text]), method compared to the weighted mean ([Formula: see text]) method. Therefore, a more accurate artifact reconstruction was provided by the auto-regression approach. Clinical Relevance- The ability to efficiently and accurately isolate evoked bioelectrical events by eliminating large artifacts is a critical advancement for the analysis of paced recordings. The developed framework allows more efficient analysis of preclinical pacing data and thereby contributes to the advancement of pacing as a clinical therapy.

A Computational Model of Biophysical Properties of the Rat Stomach Informed by Comprehensive Analysis of Muscle Anatomy.

An anatomically based 3D computational model of the rat stomach was developed using experimental muscle thickness measurements and muscle fiber orientations for the longitudinal muscle (LM) and circular muscle (CM) layers. First, 15 data points corresponding to the measurements were registered on the dorsal and ventral faces of the serosal surface of an averaged 3D rat stomach model. A thickness field representing the varying wall thickness was fitted to the surface and nodal points were projected outwards (for the LM layer) and inwards (for the CM layer) to create 2 new surfaces. In addition, a computational volume mesh was created and fiber orientation in each tetrahedral element was computed using a Laplace-Dirichlet rule-based algorithm and a simulation was performed to validate the model. The stomach model successfully represented the experimental measurements with a thickness in the range of 11.7-52.9 µm and 40.6-276.5 µm in the LM and CM layers, respectively, while the variation across the stomach was in agreement with the reported values. Similarly, the generated fiber orientations matched with the investigated fiber data and successfully resembled the observed properties such as the hairpin-like structure formed by the LM fibers in the fundus. Bioelectrical simulation using the developed model was successfully converged and reflected the properties of normal antegrade activity. In conclusion, a 3D computational model of the rat stomach was successfully developed and tested for in-silico studies. The model will be used in future studies to assess parameters in electrical therapies and to investigate the structure-function relationship in gastric motility. Clinical Relevance - Electrical stimulation is an emerging therapy for functional motility disorders. The 3D model of rat stomach developed in this study could provide accurate assessment of the efficacy of a vast range of stimulation parameters via in-silico studies and could aid in the adaptation of electrical therapies to clinical settings.

Gastric pacing response evaluated with simultaneous electrical and optical mapping.

Gastric pacing is an attractive therapeutic approach for correcting abnormal bioelectrical activity. While high-resolution (HR) electrical mapping techniques have largely contributed to the current understanding of the effect of pacing on the electrophysiological function, these mapping techniques are restricted to surface contact electrodes and the signal quality can be corrupted by pacing artifacts. Optical mapping of voltage sensitive dyes is an alternative approach used in cardiac research, and the signal quality is not affected by pacing artifacts. In this study, we simultaneously applied HR optical and electrical mapping techniques to evaluate the bioelectrical slow wave response to gastric pacing. The studies were conducted in vivo on porcine stomachs ( n=3) where the gastric electrical activity was entrained using high-energy pacing. The pacing response was optically tracked using voltage-sensitive fluorescent dyes and electrically tracked using surface contact electrodes positioned on adjacent regions. Slow waves were captured optically and electrically and were concordant in time and direction of propagation with comparable mean velocities ([Formula: see text]) and periods ([Formula: see text]). Importantly, the optical signals were free from pacing artifacts otherwise induced in electrical recordings highlighting an advantage of optical mapping. Clinical Relevance- Entrainment mapping of gastric pacing using optical techniques is a major advance for improving the preclinical understanding of the therapy. The findings can thereby inform the efficacy of gastric pacing in treating functional motility disorders.

Stress-induced neuroplasticity in the gastric response to brainstem oxytocin in male rats.

Previous studies have shown that pharmacological manipulations with stress-related hormones such as corticotropin-releasing factor and thyrotropin-releasing hormone induce neuroplasticity in brainstem vagal neurocircuits, which modulate gastric tone and motility. The prototypical antistress hormone oxytocin (OXT) has been shown to modulate gastric tone and motility via vagal pathways, and descending hypothalamic oxytocinergic inputs play a major role in the vagally dependent gastric-related adaptations to stress. The aim of this study was to investigate the possible cellular mechanisms through which OXT modulates central vagal brainstem and peripheral enteric neurocircuits of male Sprague-Dawley rats in response to chronic repetitive stress. After chronic (5 consecutive days) of homotypic or heterotypic stress load, the response to exogenous brainstem administration of OXT was examined using whole cell patch-clamp recordings from gastric-projecting vagal motoneurons and in vivo recordings of gastric tone and motility. GABAergic currents onto vagal motoneurons were decreased by OXT in stressed, but not in naïve rats. In naïve rats, microinjections of OXT in vagal brainstem nuclei-induced gastroinhibition via peripheral release of nitric oxide (NO). In stressed rats, however, the OXT-induced gastroinhibition was determined by the release of both NO and vasoactive intestinal peptide (VIP). Taken together, our data indicate that stress induces neuroplasticity in the response to OXT in the neurocircuits, which modulate gastric tone and motility. In particular, stress uncovers the OXT-mediated modulation of brainstem GABAergic currents and alters the peripheral gastric response to vagal stimulation.NEW & NOTEWORTHY The prototypical antistress hormone, oxytocin (OXT), modulates gastric tone and motility via vagal pathways, and descending hypothalamic-brainstem OXT neurocircuits play a major role in the vagally dependent adaptation of gastric motility and tone to stress. The current study suggests that in the neurocircuits, which modulate gastric tone and motility, stress induces neuroplasticity in the response to OXT and may reflect the dysregulation observed in stress-exacerbated functional motility disorders.

Analysis of Regional Variations of the Interstitial Cells of Cajal in the Murine Distal Stomach Informed by Confocal Imaging and Machine Learning Methods.

The network of Interstitial Cells of Cajal (ICC) plays a plethora of key roles in maintaining, coordinating, and regulating the contractions of the gastrointestinal (GI) smooth muscles. Several GI functional motility disorders have been associated with ICC degradation. This study extended a previously reported 2D morphological analysis and applied it to 3D spatial quantification of three different types of ICC networks in the distal stomach guided by confocal imaging and machine learning methods. The characterization of the complex changes in spatial structure of the ICC network architecture contributes to our understanding of the roles that different types of ICC may play in post-prandial physiology, pathogenesis, and/or amelioration of GI dsymotility- bridging structure and function. A validated classification method using Trainable Weka Segmentation was applied to segment the ICC from a confocal dataset of the gastric antrum of a transgenic mouse, followed by structural analysis of the segmented images. The machine learning model performance was compared to manually segmented subfields, achieving an area under the receiver-operating characteristic (AUROC) of 0.973 and 0.995 for myenteric ICC (ICC-MP; n=6) and intramuscular ICC (ICC-IM; n=17). The myenteric layer in the distal antrum increased in thickness (from 14.5 to 34μm) towards the lesser curvature, whereas the thickness decreased towards the lesser curvature in the proximal antrum (17.7 to 9 μm). There was an increase in ICC-MP volume from proximal to distal antrum (406,960±140,040 vs. 559,990±281,000μm3; p=0.000145). The % of ICC volume was similar for ICC-LM and for ICC-CM between proximal (3.6±2.3% vs. 3.1±1.2%; p=0.185) and distal antrum (3.2±3.9% vs. 2.5±2.8%; p=0.309). The average % volume of ICC-MP was significantly higher than ICC-IM at all points throughout sample (p<0.0001). The segmentation and analysis methods provide a high-throughput framework of investigating the structural changes in extended ICC networks and their associated physiological functions in animal models.

The Impact of Gastrointestinal Symptoms on Patients’ Well-Being: Best–Worst Scaling (BWS) to Prioritize Symptoms of the Gastrointestinal Symptom Score (GIS)

Background: The gastrointestinal symptom score (GIS) is used in a standardized form to ascertain dyspeptic symptoms in patients with functional dyspepsia in clinical practice. As a criterion for evaluating the effectiveness of a treatment, the change in the summed total point value is used. The total score ranges from 0 to 40 points, in which a higher score represents a more serious manifestation of the disease. Each symptom is included with equal importance in the overall evaluation. The objective of this study was to test this assumption from a patients’ perspective. Our aim was to measure the priorities of patients for the ten gastrointestinal symptoms by using best–worst scaling. Method: A best–worst scaling (BWS) object scaling (Case 1) was applied. Therefore, the symptoms of the GIS were included in a questionnaire using a fractional factorial design (BIBD—balanced incomplete block design). In each choice set, the patients selected the component that had the most and the least impact on their well-being. The BIB design generated a total of 15 choice sets, which each included four attributes. Results: In this study, 1096 affected patients were asked for their priorities regarding a treatment of functional dyspepsia and motility disorder. Based on the data analysis, the symptoms abdominal cramps (SQRT (B/W): −1.27), vomiting (SQRT (B/W): −1.07) and epigastric pain (SQRT (B/W): −0.76) were most important and thus have the greatest influence on the well-being of patients with functional dyspepsia and motility disorders. In the middle range are the symptoms nausea (SQRT (B/W): −0.69), acid reflux/indigestion (SQRT (B/W): −0.29), sickness (SQRT (B/W): −0.26) and retrosternal discomfort (SQRT (B/W): 0.26), whereas the symptoms causing the least impact are the feeling of fullness (SQRT (B/W): 0.80), early satiety (SQRT (B/W): 1.54) and loss of appetite (SQRT(B/W): 1.95). Discussion: Unlike the underlying assumption of the GIS, the BWS indicated that patients did not weight the 10 symptoms equally. The results of the survey show that the three symptoms of vomiting, abdominal cramps and epigastric pain are weighted considerably higher than symptoms such as early satiety, loss of appetite and the feeling of fullness. The evaluation of the BWS data has illustrated, however, that the restrictive assumption of GIS does not reflect the reality of dyspeptic patients. Conclusions: In conclusion, a preference-based GIS is necessary to make valid information about the real burden of illness and to improve the burden of symptoms in the indication of gastrointestinal conditions. The findings of the BWS demonstrate that the common GIS is not applicable to represent the real burden of disease. The results suggest the potential modification of the established GIS by future research using a stated preference study.

Quantification of Gastric Contractions Using MRI with a Natural Contrast Agent.

Gastric motility has an essential role in mixing and the breakdown of ingested food. It can affect the digestion process and the efficacy of the orally administered drugs. There are several methods to image, measure, and quantify gastric motility. MRI has been shown to be a suitable non-invasive method for gastric motility imaging. However, in most studies, gadolinium-based agents have been used as an oral contrast agent, making it less desirable for general usage. In this study, MRI scans were performed on 4 healthy volunteers, where pineapple juice was used as a natural contrast agent for imaging gastric motility. A novel method was developed to automatically estimate a curved centerline of the stomach. The centerline was used as a reference to quantify contraction magnitudes. The results were visualized as contraction magnitude-maps. The mean speed of each contraction wave on the lesser and greater curvatures of the stomach was calculated, and the variation of the speeds in 4 regions of the stomach were quantified. There were 3-4 contraction waves simultaneously present in the stomach for all cases. The mean speed of all contractions was 2.4±0.9 mm/s, and was in agreement with previous gastric motility studies. The propagation speed of the contractions in the greater curvature was higher in comparison to the lesser curvature (2.9±0.8 vs 1.9±0.5 mm/s); however, the speeds were more similar near to the pylorus. This study shows the feasibility of using pineapple juice as a natural oral contrast agent for the MRI measurements of gastric motility. Also, it demonstrated the viability of the proposed method for automatic curved centerline estimation, which enables practical clinical translation.Clinical Relevance- MRI is able to non-invasively provide dynamic images of the contraction patterns of the stomach, providing a novel clinical tool for assessing functional motility disorders. The use of a natural oral contrast agent such as pineapple juice, as opposed to a gadolinium-based contrast agent, makes MRI more widely accessible. Our semi-automated methods for quantifying contraction magnitude and speed will streamline analysis and clinical diagnosis.

The biliary continuum: an up-to-date look at biliary tract diseases

In the structure of gastrointestinal diseases, the pathology of the hepatobiliary system currently ranks second in frequency of occurrence. The stages of diseases of the biliary system can be combined into the so-called “biliary continuum”, when one patient has a consistent development of pathogenetically related diseases of the biliary tract. The progressive course of functional motility disorders of the biliary tract gradually leads to the development of organic pathology, including chronic cholecystitis, the subsequent development of gallstone disease and possible postcholecystectomy complications. Among the diseases of the biliary system, one of the most frequently used diagnoses is chronic cholecystitis. The development of chronic cholecystitis is associated with repeated attacks of acute inflammation or prolonged irritation of large gallstones. The clinical aspects of chronic cholecystitis and other pathologies included in the the «biliary continuum» largely depends on concomitant dyskinesia. There are several directions for the treatment of pathologies of the biliary system: diet therapy, medication, endoscopic and surgical treatment. According to the latest guidelines, the most important direction in modern therapy of diseases of the biliary system is the restoration of the motility of the biliary tract and the normalization of the physicochemical properties of bile. The central place in the treatment of diseases of the “biliary continuum” is given to antispasmodic drugs. The administration of antispasmodics is recommended in order to relieve biliary pain and dyspeptic symptoms caused by spasm of smooth muscles, as well as to control the inflammatory process due to a decrease in the release of pro-inflammatory substances. This article describes in detail the importance of the recovery of the biliary tract motor activity and the improvement of the physico-chemical properties of bile acids.

Design and Validation of a Surface-Contact Electrode for Gastric Pacing and Concurrent Slow-Wave Mapping.

Gastric contractions are, in part, coordinated by slow-waves. Functional motility disorders are correlated with abnormal slow-wave patterns. Gastric pacing has been attempted in a limited number of studies to correct gastric dysmotility. Integrated electrode arrays capable of pacing and recording slow-wave responses are required. New flexible surface-contact pacing electrodes (SPE) that can be placed atraumatically to pace and simultaneously map the slow-wave activity in the surrounding area were developed. SPE were applied in pigs in-vivo for gastric pacing along with concurrent high-resolution slow wave mapping as validation. Histology was conducted to assess for tissue damage around the pacing site. SPE were compared against temporary cardiac pacing electrodes (CPE), and hook-shaped pacing electrodes (HPE), for entrainment rate, entrainment threshold, contact quality, and slow-wave propagation patterns. Pacing with SPE (amplitude: 2 mA, pulse width: 100 ms) consistently achieved pacemaker initiation. Histological analysis illustrated no significant tissue damage. SPE resulted in a higher rate of entrainment (64%) than CPE (37%) and HPE (24%), with lower entrainment threshold (25% of CPE and 16% of HPE). High resolution mapping showed that there was no significant difference between the initiated slow-wave propagation speed for SPE and CPE (6.8±0.1 vs 6.8±0.2mm/s, P>0.05). However, SPE had higher loss of tissue lead contact quality than CPE (42±16 vs 13±10% over 20min). Pacing with SPE induced a slow-wave pacemaker site without tissue damage. SPE offered an atraumatic pacing electrode with a significant reduction of power consumption and placement time compared to impaled electrodes.

S2048 Awareness of Early Diagnosis and Surgical Management of Pediatric Intestinal Pseudo-Obstruction

INTRODUCTION: Gastrointestinal motility is produced by two types of smooths of muscles in the gastrointestinal tract which are circular muscles and longitudinal muscles. These muscles are stimulated by a complex multifaceted connection between intrinsic enteric nervous system and central nervous system. The enteric nervous system is composed of Interstitial cells of Cajal, submucosal plexus, myenteric plexus, migratory motor complex and gut neuromodulators. Gut motility disorders are derived from numerous etiologies that arise from the muscular, nervous, cellular, molecular components. Pediatric intestinal pseudo obstruction is a disorder that needs early diagnosis and prompt treatment to avoid associated life-threatening complications. CASE DESCRIPTION/METHODS: A 27 weeks gestational age baby girl born to a 25 year G1P0 mother with history of abruptio placenta and chorioamnionitis was admitted to the neonatal intensive care unit due to extreme low birth weight and prematurity. Patients developed disseminated Herpes Simplex Virus infection complicated with left grade 2 intraventricular hemorrhage. Afterwards, patient developed persistent total parenteral nutrition dependence, enteral food intolerance, marked intestinal dilation and constipation for 4 months since birth. Rectal biopsies rule out Hirschsprung disease. Multiple abdominal x-rays showed marked diffuse intestinal dilation. Water soluble enema study revealed inflammatory changes suggestive necrotizing enterocolitis. Patient was taken to the operation room since no clinical improvement. Intraoperative findings included viable intestinal tissue without ischemic change and no mechanical obstruction. After negative exploratory laparotomy we decided to perform a rigorous review of literature regarding intestinal dysmotility disorders. DISCUSSION: Our patient was diagnosed with pediatric intestinal pseudo obstruction based in our review of literature which is a intestinal motility disorder. Our plan was to perform multiple full thickness intestinal biopsies to confirmed diagnosis and surgical management with decompressive gastrostomy and ileostomy. Unfortunately, patient developed acute-clinical deterioration due to septic shock, catheter-related bacteremia and multiple organ failure. Functional motility disorders should be included as a differential diagnosis once mechanical obstruction rule out. Our aim is to provide awareness of early identification of PIPO and management since life-threatening complications may develop.

A Spatially-dense Microfabricated Photolithographic Electrode Array for Gastrointestinal Slow Wave Recordings.

Gastrointestinal slow wave activity is, in part, responsible for governing gut motility. Dysrhythmic slow wave activity has been associated with a number of functional motility disorders, but the mechanisms involved are poorly understood. There exist a number of transgenic small animal models with functional motility disorders. However, current slow wave mapping methods are targeted towards humans and large animals and are not readily translatable. To overcome these shortcomings, a novel electrode array was developed using photolithography. The developed photolithographic electrode array (PEA) was experimentally validated in vivo against a standard flexible printed circuit (FPC) array for comparison. Mean amplitudes of 0.13 ± 0.06 mV and 0.88 ± 0.05 mV were reported by the PEA and the FPC array, respectively. Mean signal to noise ratios (SNR) of 13.4 ± 6.4 dB and 8.3 ± 5.1 dB were achieved for the PEA and the FPC array, respectively. Our findings showed that the PEA acquired slow wave signals with higher amplitude and SNR. In this study, we showed that microfabrication techniques could be successfully implemented with optimized resolution for the investigation of normal and abnormal slow wave activity in smaller animals, which will enable a better understanding of the pathophysiological mechanisms and aid in the diagnosis and treatment of gastrointestinal motility disorders.Clinical Relevance - The ability to characterize the slow wave activity in transgenic animals with functional motility disorders would be a critical advance for the diagnosis and treatment of these disorders. Microfabrication techniques enable miniaturization of high-resolution electrode arrays suitable for mapping electrical activity in normal and transgenic small laboratory animals such as rats and mice.

High-Resolution Mapping of Intestinal Spike Bursts and Motility.

Gastrointestinal (GI) motility and functional disorders affect up to 25% of the American population. Electrophysiological studies had shown a link between these functional motility disorders and abnormalities in GI bioelectrical activity. However, the dynamics between GI electrical activity (slow waves and spike bursts) and motility are not well understood. This study presents a framework to simultaneously record and quantify GI spike bursts and motility in vivo, in high-resolution. The dynamics between spike burst events and motility observed in 4 pig studies were investigated. A clear connection between spike burst patches and localized contractions was observed. The dataset consisted of 685 spike burst events in 191 patches. Contractions were associated with 81 patches. Spike burst patches associated with contractions had significantly higher amplitude, duration, and size compared to the ones that did not show an association. The amplitude, duration, and size of spike burst patches were positively correlated with the contraction strength. The spike burst patch energy displayed the highest correlation (r = 0.74). The contraction strength had a linear trend with spike burst patch energy. However, it could only account for 52% of the variance in contraction strength.

A Framework for Spatiotemporal Analysis of Gastrointestinal Spike Burst Propagation.

Gastrointestinal spike bursts are a bioelectrical phenomenon associated with motility. These events when initiated propagate a small distance and abruptly terminate activating a small area defined as a patch. Understanding normal and abnormal propagation patterns of these events may shed light on the root causes of functional motility disorders. This study develops an automated framework for spatiotemporal analysis of spike bursts. High-resolution electrical signals were obtained from the pig intestine, after which intestinal spike bursts were identified and clustered into their propagating wavefronts. Propagation velocity was estimated by fitting a polynomial surface to the activation times. The fit was able to estimate the velocity of spike burst patches covering at least six channels with an average RMSE of 0.4 s. Propagation within patches was visualized by plotting the fit as activation maps and velocity maps. Average velocities were calculated to compare the propagation characteristics of different types of patches. In the future, this framework will be extended to generate amplitude maps and spike burst duration maps. These tools can be used to analyze spike patch propagation and their relationship to motility.

A Novel Gastric Pacing Device to Modulate Slow Waves and Assessment by High-Resolution Mapping.

The use of electrical pacing in the gastrointestinal field continues to advance clinical and basic science; however, the efficacy and effectiveness of gastric stimulation and pacing remains limited. In the stomach, rhythmic bioelectrical events, known as slowwaves, coordinate the muscular contractions that aid digestion. A range of slow wave abnormalities have been shown to be associated with functional motility disorders, such as gastroparesis, chronic unexplained nausea and vomiting, and functional dyspepsia. Pacing is an attractive therapeutic approach to revert slow wave abnormalities. However, there are currently no clinical gastric pacing devices in active use. In this study, a novel battery-powered pacing device was developed, implementing wireless control and tissue electrical parameter monitoring. The pacing device was applied in five pigs in vivo along with high-resolution (HR) mapping to validate the device and to elucidate the pacing response of slow waves. The pacing leads were placed in the middle of the HR array to determine any changes to the propagation pattern. The pacing period range was 14-30 s. In all studies, the novel pacing device initiated slow wave activation from a location near the pacing leads at the specified period. Slow wave propagation speed increased after pacing (from 6.4 ± 2.0 to 8.1 ± 3.2mm/s; P<0.001), commensurate with induction of paced anisotropic propagation. This study introduces a novel gastric pacing system suitable for clinical trials, achieving reliable induction of slow wave pacing at specific location and periods. The device is now available to be trialed as a therapeutic application for motility disorders and obesity.