Engaging biological oscillators through second messenger pathways permits emergence of a robust gastric slow-wave during peristalsis

Peristalsis, the coordinated contraction—relaxation of the muscles of the stomach is important for normal gastric motility and is impaired in motility disorders. Coordinated electrical depolarizations that originate and propagate within a network of interconnected layers of interstitial cells of Cajal (ICC) and smooth muscle (SM) cells of the stomach wall as a slow-wave, underly peristalsis. Normally, the gastric slow-wave oscillates with a single period and uniform rostrocaudal lag, exhibiting network entrainment. Understanding of the integrative role of neurotransmission and intercellular coupling in the propagation of an entrained gastric slow-wave, important for understanding motility disorders, however, remains incomplete. Using a computational framework constituted of a novel gastric motility network (GMN) model we address the hypothesis that engaging biological oscillators (i.e., ICCs) by constitutive gap junction coupling mechanisms and enteric neural innervation activated signals can confer a robust entrained gastric slow-wave. We demonstrate that while a decreasing enteric neural innervation gradient that modulates the intracellular IP3 concentration in the ICCs can guide the aboral slow-wave propagation essential for peristalsis, engaging ICCs by recruiting the exchange of second messengers (inositol trisphosphate (IP3) and Ca2+) ensures a robust entrained longitudinal slow-wave, even in the presence of biological variability in electrical coupling strengths. Our GMN with the distinct intercellular coupling in conjunction with the intracellular feedback pathways and a rostrocaudal enteric neural innervation gradient allows gastric slow waves to oscillate with a moderate range of frequencies and to propagate with a broad range of velocities, thus preventing decoupling observed in motility disorders. Overall, the findings provide a mechanistic explanation for the emergence of decoupled slow waves associated with motility impairments of the stomach, offer directions for future experiments and theoretical work, and can potentially aid in the design of new interventional pharmacological and neuromodulation device treatments for addressing gastric motility disorders.

Engaging Biological Oscillators through Second Messenger Pathways Permits Emergence of a Robust Gastric Slow-Wave during Peristalsis

Peristalsis, the coordinated contraction-relaxation of the muscles of the stomach, is important for normal gastric motility and is impaired in motility disorders. Coordinated electrical depolarizations that originate and propagate within a network of interconnected layers of interstitial cells of Cajal (ICC) and smooth muscle (SM) cells of the stomach wall as a slow-wave, underly peristalsis. Normally, the gastric slow-wave oscillates with a single period and uniform rostrocaudal lag, exhibiting network entrainment. Understanding of the integrative role of neurotransmission and intercellular coupling in the propagation of an entrained gastric slow-wave, important for understanding motility disorders, however, remains incomplete. Using a computational framework constituted of a novel gastric motility network (GMN) model we address the hypothesis that engaging biological oscillators (i.e., ICCs) by constitutive gap junction coupling mechanisms and enteric neural stimulus activated signals can confer a robust entrained gastric slow-wave. We demonstrate that while a decreasing enteric neural stimulus gradient that modulates the intracellular IP3 concentration in the ICCs can guide the aboral slow-wave propagation essential for peristalsis, engaging ICCs by recruiting the exchange of second messengers (inositol trisphosphate (IP3) and Ca2+) ensures a robust entrained longitudinal slow-wave, even in the presence of biological variability in coupling strengths. Our GMN with the distinct intercellular coupling in conjunction with the intracellular feedback pathways and a rostrocaudal enteric neural stimulus gradient allows gastric slow waves to oscillate with a moderate range of frequencies and to propagate with a broad range of velocities, thus preventing decoupling observed in motility disorders. Overall, the findings provide a mechanistic explanation for the emergence of decoupled slow waves associated with motility impairments of the stomach, offer directions for future experiments and theoretical work, and can potentially aid in the design of new interventional pharmacological and neuromodulation device treatments for addressing gastric motility disorders.

Clinical Associations of Functional Dyspepsia with Gastric Dysrhythmia on Electrogastrography: A Comprehensive Systematic Review and Meta-Analysis

BackgroundFunctional dyspepsia (FD) is a common gastroduodenal disorder, yet its pathophysiology remains poorly understood. Bioelectrical gastric slow wave abnormalities are thought to contribute to its multifactorial pathophysiology. Electrogastrography (EGG) has been used to record gastric electrical activity, however the clinical associations require further evaluation.AimsThis study aimed to systematically assess the clinical associations of EGG in FD.MethodsMEDLINE, EMBASE, and CENTRAL databases were systematically searched for articles using EGG in adults with FD. Primary outcomes were percentage normal vs abnormal rhythm (bradygastria, normogastria, tachygastria). Secondary outcomes were dominant power, dominant frequency, percentage coupling and the meal responses.Results1751 FD patients and 555 controls from 47 studies were included. FD patients spent less time in normogastria while fasted (SMD −0.74; 95%CI −1.22 - −0.25) and postprandially (−0.86; 95%CI −1.35 - −0.37) compared to controls. FD patients also spent more fasted time in bradygastria (0.63; 95%CI 0.33 – 0.93) and tachygastria (0.45; 95%CI 0.12 – 0.78%). The power ratio (−0.17; 95%CI −0.83 - 0.48), and dominant frequency meal-response ratio (0.06; 95%CI −0.08 - 0.21) were not significantly different to controls. Correlations between EGG metrics and the presence and timing of FD symptoms were inconsistent. EGG methodologies were diverse and variably applied.ConclusionAbnormal gastric slow wave rhythms are a consistent abnormality present in FD, as defined by EGG, and therefore likely play a role in pathophysiology. The aberrant electrophysiology identified in FD warrants further investigation, including into underlying mechanisms, associated spatial patterns, and symptom correlations.

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.

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.