Antral Motility Research Articles

Alterations in gastrointestinal motility assessed by high-resolution antroduodenal manometry in patients with severe disorders of gut-brain interaction.

Data are limited regarding gastrointestinal motility disturbance in disorders of gut-brain interaction (DGBI). This study aimed to characterize antroduodenal motor alterations in patients with high-resolution antroduodenal manometry (HR-ADM). HR-ADM was performed in patients with severe DGBI and compared with healthy volunteers (HV). HR-ADM used a commercially available probe composed of 36 electronic sensors spaced 1 cm apart and positioned across the pylorus. Antral and duodenal motor high-resolution profiles were analyzed, based on the frequency, amplitude, and contractile integral/sensor (CI/s) calculated for each phase of the migrating motor complex (MMC). Eighteen HV and 64 patients were investigated, 10 with irritable bowel syndrome (IBS), 24 with functional dyspepsia (FD), 15 with overlap IBS-FD, and 15 with other DGBI. Compared with HV, patients had a lower frequency of phase II duodenal contractions (27 vs. 51 per hour; P = 0.002) and a lower duodenal phase II contraction amplitude (70 vs. 100 mmHg; P = 0.01), resulting in a lower CI/s of phase II (833 vs. 1,901 mmHg·cm·s; P < 0.001) in the duodenum. In addition, the frequency of phase II propagated antroduodenal contractions was lower (5 vs. 11 per hour; P < 0.001) in patients compared with HV. Interestingly, the antral CI/s of phase III was decreased in FD patients but not in IBS patients. Patients with severe DGBI display alterations in antral and intestinal motility assessed by commercially available HR-ADM. Whether these alterations may explain symptom profiles in such patients remains to be confirmed (NCT04918329 and NCT01519180).NEW & NOTEWORTHY Gastrointestinal dysmotility has been assessed poorly in disorders of gut-brain interaction (DGBI), especially with high-resolution antroduodenal manometry. Plots of DGBI patients showed lower duodenal contractions during phase II regarding amplitude, frequency, and contractile integral/sensor (CI/s) compared with healthy volunteers. A lower frequency of propagated antroduodenal contractions was also reported. Finally, antral CI/s was lower in patients with functional dyspepsia during phase III. Further studies are needed to assess the clinical significance of these alterations.

Extensive scintigraphic gastric motor function testing with concurrent symptom recording predicts prospectively measured daily dyspeptic symptoms.

Absent "organic" disease, dyspeptic symptoms may arise from abnormal gastric sensation, accommodation, motility or emptying (GE). Extensive gastric sensorimotor evaluation is rarely undertaken because testing is prolonged, invasive, poorly tolerated or unavailable. To investigate whether gastric antral motor function, evaluated with scintigraphy, predicts GE. To explore whether motor testing with symptom recording predicts day-to-day symptoms in patients with dyspepsia. GE was determined using a scintigraphic solid-meal protocol (296 kcal, 35% fat). Antral motility was estimated from 10 min of scintigraphic time-activity curves acquired 40 min after meal consumption. An antral motility index (MI) was derived from contraction amplitude and frequency. Intra-gastric distribution of the meal on scintograms at 1 h (IGD1) was determined. Meal-induced symptoms were evaluated by questionnaire. Patients completed the Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD) for 14 days. Twelve healthy participants and 23 prospectively recruited patients completed the study. Nine patients had delayed, and 2 had rapid, GE. In univariate analysis MI explained 42% of GE half-time. In multivariate analysis MI and GE half-time explained 25% of the variance in meal-induced symptoms. While scintigraphic evaluation of gastric motor function with symptom recording explained 80% of the variance in the GCSI-DD, meal-induced symptoms were the only significant predictor. However, among patients with delayed GE, MI, GE half-time, IGD1, and meal-induced symptoms all significantly predicted GCSI-DD. Antral motility predicts GE. In exploratory analyses, only meal-induced symptoms predicted daily symptoms among patients with dyspepsia. However, motor function also predicted symptoms in patients with delayed GE.

Effects of Chinese ginger Alpinia officinarum-based phytopharmaceutical compound on gastric motility

BackgroundAlpinia officinarum, better known as Chinese ginger, is used for the treatment of gastrointestinal disorders in traditional Chinese and Ayurveda medicine. However, scientific evidence of an effect on gastrointestinal motility is missing. PurposeThis study aimed to estimate the effect of a phytopharmaceutical compound (PPC) based on Alpinia officinarum on gastric motility in vitro in order to assess its potential use in the treatment of functional dyspepsia. Study DesignWe investigated to which extent the compound affects the activity of gastric smooth muscle and we identified involved mediating cellular mechanisms. MethodsBasal and stimulated muscle activity were recorded from muscle-myenteric plexus preparations from three different regions of the guinea pig stomach before and after incubation with different concentrations of the PPC in an organ bath setup. Effect-mediating mechanisms were investigated by pharmacology. ResultsPPC exhibited a smooth muscle relaxation in a concentration-dependent manner. This was region- and muscle type specific as it was greater in fundus and corpus than in antrum and more pronounced in the circular than in the longitudinal muscle layer. The effect was primarily myogenic and at least partly mediated by TRPA1. ConclusionThe investigated PPC reduces basal tone particularly of fundus smooth muscle in a non-neuronal manner by inhibiting calcium influx via TRPA1, without affecting antral motility. Based on these data, Alpinia officinarum could be considered for phytopharmaceutical treatment of functional dyspepsia.

Physiological characterization of gastric emptying using high-resolution antropyloroduodenal manometry.

Delayed gastric emptying (GE) has been associated with antral and pyloric dysmotility. We aimed to characterize differences in the antral, duodenal, and pyloric motility profiles associated with delayed GE, using high-resolution antropyloroduodenal manometry (HR-ADM). Patients referred for HR-ADM for dyspeptic symptoms performed a concurrent GE breath test (NCT01519180 and NCT04918329). HR-ADM involved 36 sensors 1 cm apart, placed across the pylorus. Interdigestive and postprandial periods were identified. Antral, pyloric, and duodenal motor profiles were analyzed recording the frequency, amplitude, and propagative nature of contractions for each period. Plots of patients with normal and delayed GE were compared. Sixty patients underwent both HR-ADM and GE tests. Twenty-five and 35 patients had delayed and normal GE, respectively. Antral and duodenal motor profiles were not different between the two groups during the interdigestive period. During the postprandial period, a lower frequency of antral contractions was associated with delayed GE (2.22 vs. 1.39 contractions/min; P = 0.002), but no difference in mean contraction amplitude was observed. The pyloric region was identified in all the patients and pylorospasms, defined as 3 min of repeated isolated pyloric contractions, were more frequent in patients with delayed GE (32.0% vs. 5.7%; P = 0.02) during the postprandial period. No difference in duodenal contraction profiles was observed. Manometric profile alterations were observed in 72% of the patients with delayed GE, with 56% having a low frequency of antral contractions. Using HR-ADM, patients with delayed GE displayed different postprandial antropyloric motility as compared with patients with normal GE.NEW & NOTEWORTHY High-resolution antropyloroduodenal manometry (HR-ADM) allows precise characterization of antral, pyloric, and duodenal motility, although its association with gastric emptying (GE) has been poorly investigated. Concurrent HR-ADM with GE measurement showed a lower frequency of antral postprandial contractions and an increased frequency of postprandial pylorospasms in patients with delayed GE. HR-ADM could, therefore, be useful in the future to better select patients for treatments targeting the pylorus.

The Clinical Utility of Antroduodenal Manometry in the Evaluation of Children with Upper Gastrointestinal Symptoms.

Antroduodenal manometry (ADM) measures antral and small bowel motility and is clinically used to evaluate upper gastrointestinal (UGI) symptoms. We aimed to evaluate its utility in guiding treatment, predicting response, and association with clinical findings. Retrospective review of 200 children undergoing ADM. ADM interpretation and parameters were compared to outcomes (response to first therapy after ADM and overall response), predominant symptom (group A, abdominal distention and/or vomiting and group B, abdominal pain and/or nausea), etiology (idiopathic or with known comorbidity), and ADM indication [suspected chronic intestinal pseudo-obstruction (CIPO) or unexplained UGI symptoms]. We found an association between a normal intestinal phase III of the migrating motor complex (MMC) and idiopathic etiology, group B symptoms and unexplained UGI symptoms. No variable was associated with initial successful response. However, normal small bowel phase III of the MMC and idiopathic etiology were associated with overall successful response to treatment (including feeding tolerance and weaning of parenteral nutrition). No antral ADM parameter was associated with outcomes or other comparisons. The time to overall successful treatment response was significantly shorter in patients with a normal ADM and presence of a normal phase III of the MMC. The presence of the phase III of the MMC was the single ADM parameter predictive of overall treatment response, also associated to group B symptoms and idiopathic etiology. Our findings suggest that small bowel ADM parameters are more useful to predict outcomes and ADM should be performed primarily in patients presenting with abdominal distention and/or vomiting and those being evaluated for CIPO.

StomachSim: An in-silico simulator of gastric biomechanics with application to pyloroplasty

Aim: We have developed StomachSim, an in-silico simulator that is designed to simulate the biomechanics and fluid mechanics of a wide range of gastric conditions as well as gastric surgical procedures. Here we demonstrate its use in quantifying the effects of motility disorders and pyloroplasty on the hydrolysis and emptying of a liquid meal inside the stomach. Methods: A physiologically realistic model of the stomach, including the antral motility, is synthesized based on in-vivo imaging, and the mixing and gastric emptying are simulated using computational fluid dynamics (CFD). The enzymatic biochemistry for protein hydrolysis is also implemented by incorporating the secretion of a proteolytic enzyme from the proximal stomach walls and the subsequent enzymatic reaction with the protein dissolved in the liquid meal. Using this model, we measured the effect of stomach motility and the diameter of the pyloric orifice on the retropulsive and pyloric jets, the rate of hydrolysis in different regions, and the emptying of gastric contents. Results: This study presents a proof-of-concept for the application of StomachSim in gastric disorders and surgeries. The emptying rate of our model for the healthy case agreed with the in-vivo measurements of similar caloric density liquid meals. A stomach with a 50% lower motility amplitude had a 35% lower net emptying rate and a 41% lower emptying rate of the hydrolyzed protein. Furthermore, the emptying rate showed a non-linear variation with respect to the motility of the stomach. For a simulated pyloroplasty procedure where the pyloric orifice diameter is doubled and the orifice stays open permanently, the emptying rate of the lower motility case doubled over its original value. Conclusion: StomachSim offers a novel and potentially effective modality for examining the effect of gastric conditions and gastric surgical procedures on gastric function. Our simulations show that gastroparesis and pyloroplasty not only affect the emptying rate but also alter the mixing of contents thereby changing the rate of hydrolysis. The model helped quantify the changes in the flow of contents in the antro-duodenal region for varying degrees of gastroparesis and pyloroplasty. The authors acknowledge support from NSF award CBET 2019405 and NIH award 1R21GM139073-01. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Fourier Phase Analysis of Dynamic Antral Contraction Scintigraphy: New Software, Reference Values, and Comparisons to Conventional Gastric Emptying.

Dynamic antral contraction scintigraphy (DACS) has been used to evaluate for gastric dysmotility by measuring antral contraction frequency and ejection fraction (EF). Fourier phase image analysis has the potential to assess gastric antral contractions for dyssynchrony as has been used for analyzing nuclear cardiology ventriculography (multigated acquisition studies) for cardiac dyssynchrony. The aims of this study were to determine whether Fourier phase analysis helps to characterize antral motility physiology, whether Fourier phase analysis correlates with conventional gastric emptying scintigraphy (GES), and which DACS parameters may aid in diagnosing gastric dysmotility, particularly delayed gastric emptying (GE). Methods: DACS and GES of healthy volunteers (n = 22) were compared with patients (n = 99) with symptoms of gastroparesis. New DACS Fourier phase analysis software was developed. Results: GE was delayed (n = 53) or normal (n = 46) in patients. There was a linear correlation between the time for the stomach to empty 50% of the meal and the percentage total proximal and distal in-phase antral pixels at 30 min (r = 0.37, P = 0.0001) and 60 min (r = 0.26, P = 0.007). In healthy volunteers, the mean proximal-to-distal ratio of in-phase antral pixels increased from 1.67 (30 min) to 2.65 (120 min) (P = 0.035), and EF increased from 23% (30 min) to 32% (120 min) (P = 0.022). Multivariable regressions of percentage total proximal and distal in-phase antral pixels (30 min) and EF (60 min) were the best predictors of abnormal GE (adjusted odds ratio, 3.30 [95% CI, 1.21-9.00] and 2.97 [95% CI, 1.08-8.21], respectively). Conclusion: This study used Fourier phase analysis to analyze DACS in healthy volunteers and patients with symptoms of gastroparesis. In addition to establishing reference values, new physiologic information on antral motility was obtained. In healthy volunteers, there was an increasing proximal-to-distal ratio of in-phase antral pixels and antral EF over time after meal ingestion. The percentage total proximal and distal in-phase antral pixels at both 30 and 60 min correlated well with GE values for the time for the stomach to empty 50% of the meal. For symptomatic patients, the percentage total proximal and distal in-phase antral pixels at 30 min and the EF at 60 min after meal ingestion correlated with delayed GE on conventional GES. Thus, Fourier phase analysis of DACS appears to have potential to further aid in diagnosing gastric dysmotility in GES.

Impact of Objective Colonic and Whole Gut Motility Data as Measured by Wireless Motility Capsule on Outcomes of Antireflux Surgery.

Studies show higher rates of dissatisfaction with antireflux surgery (ARS) outcomes in patients with chronic constipation. This suggests a relationship between colonic dysmotility and suboptimal surgical outcome. However, due to limitations in technology, there is no objective data available examining this relationship. The wireless motility capsule (WMC) is a novel technology consisting of an ingestible capsule equipped with pH, temperature, and pressure sensors, which provide information regarding regional and whole gut transit times, pH and motility. The aim of this study was to assess the impact of objective regional and whole gut motility data on the outcomes of ARS. This was a retrospective review of patients who underwent WMC testing before ARS. Transit times, motility, and pH data obtained from different gastrointestinal tract regions were used in analysis to determine factors that impact surgical outcome. A favorable outcome was defined as complete resolution of the predominant reflux symptom and freedom from antisecretory medications. The final study population consisted of 48 patients (fundoplication [n = 29] and magnetic sphincter augmentation [n = 19]). Of those patients, 87.5% were females and the mean age ± SD was 51.8 ± 14.5 years. At follow-up (mean ± SD, 16.8 ± 13.2 months), 87.5% of all patients achieved favorable outcomes. Patients with unfavorable outcomes had longer mean whole gut transit times (92.0 hours vs 55.7 hours; p = 0.024) and colonic transit times (78.6 hours vs 47.3 hours; p = 0.028), higher mean peak colonic pH (8.8 vs 8.15; p = 0.009), and higher mean antral motility indexes (310 vs 90.1; p = 0.050). This is the first study to demonstrate that objective colonic dysmotility leads to suboptimal outcomes after ARS. WMC testing can assist with preoperative risk assessment and counseling for patients seeking ARS.

Effects of Simo decoction on gastric motility of diabetic rats.

To investigate the effects of simo decoction (SMD) on the gastric motility of diabetic rats. Diabetic rats were gavaged with various doses of SMD (0.15, 1.5, and 3.0ml/kg/d) or saline, and their blood glucose levels and body weight were monitored. Gastric emptying and antral motility were assessed by phenol red retention and contractions of antral strips, respectively. The levels of substance P (SP), vasoactive intestinal peptide (VIP), and neurogenic nitric oxide synthase (nNOS) in the gastric antrum were determined by real-time polymerase chain reaction and Western blot. Gastric emptying was delayed in diabetic rats (p< 0.01 vs. non-diabetic controls) but accelerated after SMD administration (p< 0.01). The contractions of antral strips were reduced in diabetic rats (p< 0.01 vs. non-diabetic controls) but improved after SMD intervention (p< 0.05). The mRNA expressions of SP, VIP, and nNOS in diabetic rats were downregulated compared with non-diabetic controls (all p< 0.01). Simo decoction treatment did not affect the expression of these factors in diabetic rats. The protein levels of SP, VIP, and nNOS in diabetic rats were decreased (p< 0.01), increased (p< 0.01), and comparable (p> 0.05), respectively, in comparison with non-diabetic controls. Simo decoction administration increased SP protein expression (p< 0.01) and decreased the levels of VIP (p< 0.01) and nNOS (p< 0.01) in diabetic rats. Simo decoction improved gastric dysmotility of diabetic rats possibly by upregulating SP and downregulating VIP and nNOS.

Rubiscolin‑6 rapidly suppresses the postprandial motility of the gastric antrum and subsequently increases food intake via δ‑opioid receptors in mice

Rubiscolin-6 is a food-derived opioid peptide found in Spinacia oleracea that has anti-nociceptive, memory-enhancing, anxiolytic-like and anti-depressant effects. Rubiscolin-6 has been reported to have two opposing effects on food intake. Food intake is closely connected to gut motility; however, to the best of our knowledge, the effect of rubiscolin-6 on gut motility has not been reported. The present study aimed to investigate the effect of rubiscolin-6 on postprandial motility of the gastric antrum in conscious mice. A catheter was implanted in the gastric antrum of male C57BL/6J mice. Manometric measurements were performed in fasted male mice and chow was then provided to assess motility in the fed state. Rubiscolin-6, the δ-opioid receptor antagonist naltrindole, a mixture of rubiscolin-6 and naltrindole, or vehicle was administered intraperitoneally 30 min after eating. The percentage motor index (%MI) was then calculated. Cumulative food intake was measured in both ad libitum-fed and overnight-fasted mice. The %MI was significantly lower in mice treated with rubiscolin-6 compared with that in the other groups, but normalized by treatment with the rubiscolin-6/naltrindole mixture. The decrease in %MI induced by rubiscolin-6 remained for 1 h after administration. Cumulative food intake was significantly higher 4 and 6 h after rubiscolin-6 administration in ad libitum-fed mice but was normalized by the rubiscolin-6/naltrindole mixture. Food intake 30 min after rubiscolin-6 administration was normal, but was higher in mice treated with the rubiscolin-6/naltrindole mixture. Thus, rubiscolin-6 may have a rapid effect to reduce postprandial antral motility and may subsequently increase food intake after this inhibitory effect disappears. These effects were revealed to be mediated through δ-opioid receptors. The orexigenic effect of rubiscolin-6 may be applicable to the treatment of anorexia and cachexia.

The effects of abdominal-based early progressive mobilisation on gastric motility in endotracheally intubated intensive care patients: A randomised controlled trial

ObjectiveTo examine whether an abdominal-based early progressive mobilisation program improves gastric motility and reduces feeding intolerance in critically ill patients with endotracheal intubation. Design and MethodsA randomised controlled trial was designed. Adult patients admitted to the intensive care unit who were intubated and had an order for enteral nutrition were randomly assigned to partake in an three stages of abdominal-based progressive mobilisation program (passive abdominal massage, bed-side bicycle and ambulating) or standard of care. Gastric antral motility was measured by bedside ultrasound. ResultsA total of 83 critically ill patients were included in the study. The intervention group displayed a statistically significant improvement in the antral motility index than the control group (p < .001), as well as in complications of feeding intolerance, including the incidence of abdominal distention (9.8% vs 33.3%, p = .009), vomiting (0% vs 16.7%, p = .019) and diarrhoea (22% vs 50%, p = .008). However, no significant difference for the full enteral feeding rate on the third day was observed between the groups.Furthermore, time on mechanical ventilation (4.52 ± 2.77 days vs 6.24 ± 3.90 days, p = .023) was shorter in intervention group, but no significant difference of length of intensive care unit stay was observed between the groups. ConclusionsImplementation of an abdominal-based early progressive mobilisation program can improve gastric motility and feeding intolerance in critically ill patients with an endotracheal tube.

Transpyloric propagation and liquid gastric emptying in children with foregut dysmotility.

Gastric emptying (GE) requires precise antropyloroduodenal coordination for effective transpyloric flow, the mechanisms of which are still unclear. We aimed to correlate gastric antral function assessed by antroduodenal manometry (ADM) with GE scintigraphy (GES) for liquid feeds in children with suspected gastrointestinal dysmotility. Children who underwent both ADM and GES over a five-year period were reviewed. ADM tracings were re-analyzed to assess antral frequency, amplitude, and motility index (MI) pre-prandially and postprandially. Transpyloric propagation (TPP) was defined as antegrade propagated antral activity preceding duodenal phase III of the migrating motor complex (MMC). TPP was defined as "poor" if occurring in <50% of all presented duodenal phases III. For GES, regions of interest over the whole stomach, fundus, and antrum were drawn to calculate GE half-time (GE-T1/2 ) and retention rate (RR) in each region at 1 and 2h. Forty-seven children (median age: 7.0years) were included. Twenty-two had PIPO, 14 functional GI disorders, and 11gastroparesis. Children with poor TPP had longer GE-T1/2 (113.0 vs 66.5min, p=0.028), higher RR of the whole stomach and fundus at 1h (79.5% vs 63.5%, p=0.038; 60.0% vs 41.0%, p=0.022, respectively) and 2h (51.0% vs 10.5%, p=0.005; 36.0% vs 6.5%, p=0.004, respectively). The pre-prandial antral amplitude of contractions inversely correlated with GE-T1/2 , RR of the whole stomach, and fundus at 2h. TPP during phase III of the MMC correlated with gastric emptying of liquid and its assessment on ADM might predict abnormalities in postprandial gastric function.

Ultrasonographic evaluation of the effects of azithromycin on antral motility and gastric emptying in healthy cats.

BackgroundErythromycin, a macrolide antibiotic with motilin agonist properties, shortens gastric emptying (GE) time in healthy cats. Azithromycin, another macrolide antibiotic, is effective for treatment of gastric paresis in people.ObjectivesTo evaluate the effects of azithromycin on GE and gastric motility in healthy cats in comparison with erythromycin (positive control) and placebo.AnimalsEight healthy purpose‐bred cats.MethodsProspective, blinded, crossover study. Cats received either azithromycin (3.5 mg/kg PO q24h), erythromycin (1 mg/kg PO q8h), or placebo for 24 hours before and during evaluation of GE. A validated method using ultrasound for sequential measurements of antral area as well as amplitude and frequency of contractions was used to assess GE and evaluate gastric antral motility postprandially over an 8‐hour period.ResultsGE was significantly faster (P < .05) after administration of azithromycin and erythromycin when compared to placebo in the late phase of fractional emptying from 75% (mean ± SD: 327 ± 51 minutes, 327 ± 22 minutes, and 367 ± 29 minutes, respectively), to 95% fractional emptying (399 ± 52 minutes, 404 ± 11 minutes, and 444 ± 24 minutes, respectively). The drugs had no significant effect on antral motility variables at any time point.Conclusions and Clinical ImportanceAzithromycin and erythromycin shorten GE time in a comparable manner in healthy cats. Evaluation of their efficacy in cats with gastric dysmotility is warranted.

Comparative Effectiveness of Intravenous Azithromycin Versus Erythromycin Stimulating Antroduodenal Motility in Children.

Azithromycin has been shown to improve gastrointestinal motility in adults and may have fewer drug interactions and reduced arrhythmogenic effects than erythromycin. We hypothesized that azithromycin is comparable to erythromycin in eliciting pharmacodynamic outcomes for antral and small bowel motility. To compare the pharmacodynamic effectiveness of azithromycin and erythromycin for eliciting antral and duodenal motility in pediatric patients who underwent antroduodenal manometry for different indications. We conducted a retrospective comparison of clinic data and manometric pharmacodynamics outcomes in patients who underwent antroduodenal manometry between 2013 and 2017. Fifty-one patients mean age (± standard deviation) 9.7 (5.4) years, received either azithromycin 3 mg/kg (n = 20) or erythromycin 2 mg/kg (n = 31) during antroduodenal manometry. For patients receiving erythromycin, mean area under the curve (AUC) across all eight pressure ports increased from median [95% confidence interval] 2256 [1585, 2602] to 8742 [5876, 11761] mmHg × s (P < 0.001) and mean motility index increased from 8.63 [7.87, 9.42] to 11.98 [11.20, 12.21] (P < 0.001). For patients receiving azithromycin, mean AUC increased from 2255 [1585, 2602] to 8254 [5649, 10470] mmHg × s (P < 0.001) and motility index increased from 8.63 [7.87,9.42] to 11.79 [11.03, 12.21] (P < 0.001). Neither mean stimulated AUC nor mean motility index was significantly different between azithromycin and erythromycin treatments. There was no significant difference in side effects between groups. Azithromycin and erythromycin have similar pharmacodynamic effects on antral and small bowel contractility in children. Azithromycin should be considered an acceptable alternative to erythromycin as an upper gastrointestinal tract prokinetic for children and has historically had fewer side effects than erythromycin.

Effects of Provocative Testing on Phase III Migrating Motor Complex in Children.

Antroduodenal manometry (ADM) is used to evaluate antral and small intestinal motility, with the presence of phase III migrating motor complexes (MMCs) indicating an intact enteric neuromuscular system. The lack of evidence-based or consensus-driven established norms for MMC in fasting phase and after provocative testing marks a major limitation in the interpretation of ADM studies. We aimed to determine the characteristics of MMC in fasting and post-provocative phase in children. Data from subjects ages <20 years with ADM results evaluated at neuro-gastroenterology and Motility Disorders Center, Cincinnati Children's Hospital Medical Center from January 2018 to March 2019 were analyzed. Forty-eight ADM tracings that did not demonstrate abnormal patterns were included; the mean age was 10.00 ± 5.72 years and 50% were male. Indications for ADM included: vomiting (27.1%), feeding intolerance (27.1%), abdominal pain (16.6%), nausea (14.6%), and abdominal distension (14.6%). Thirty-seven percent of subjects had enteral access for feeds. During fasting, one-third of all MMC originated in the antrum. Azithromycin-induced MMC occurred in 28% of subjects and two-thirds of these originated in the antrum with antral contractions of significantly higher frequency and amplitude compared to fasting. Octreotide significantly increased frequency, amplitude, and duration of MMC compared to fasting, with 76% originating in the antrum. Both azithromycin and octreotide induced more than one MMC in a third of subjects. We describe the characteristics of antral and small intestinal motility during fasting and after provocative testing in children. These values will help standardize our interpretation of pediatric ADM studies.

Electroacupuncture at ST36 Improve the Gastric Motility by Affecting Neurotransmitters in the Enteric Nervous System in Type 2 Diabetic Rats.

Electroacupuncture (EA) can effectively relieve hyperglycemia and gastric emptying disorders in diabetic gastroparesis (DGP). However, the effect of EA on type 2 diabetes mellitus (T2DM) gastroparesis and its mechanism in the enteric nervous system (ENS) are rarely studied. We investigated the therapeutic effect of EA at ST36 and its effect on the main inhibitory and excitatory neurotransmitters in the ENS in DGP rats. Male Sprague-Dawley (SD) rats were fed a high-fat diet for 2 weeks and injected with streptozotocin (STZ) at 35 mg/kg to induce T2DM. T2DM rats were divided into the diabetic mellitus (DM) group and the EA group. The control (CON) group comprised normal rats without any intervention. EA treatment was started 6 weeks after the induction of DM and continued for 5 weeks. The body weight and food intake of the rats were recorded every week. Blood glucose, insulin, glucose tolerance, gastric emptying, and antral motility were measured after treatment. The expression of protein gene product 9.5 (PGP9.5), neuronal nitric oxide synthase (nNOS), and choline acetyltransferase (ChAT) in gastric antrum were quantified by western blotting and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The T2DM gastroparesis model was successfully established. EA treatment reduced the body weight, food intake, and blood glucose; improved glucose intolerance and insulin resistance; increased the gastric emptying rate, the mean antral pressure, and the amplitude of antral motility; and decreased the frequency of antral motility compared with those in the DM group. EA treatment increased the expression level of nNOS, ChAT, and PGP9.5 proteins, and nNOS and ChAT mRNA. The results suggested that EA at ST36 could ameliorate DGP, partly restore the damage to general neurons, and increase nNOS and ChAT in the gastric antrum. EA improved DGP partly via reducing the loss of inhibitory and excitatory neurotransmitters in the ENS.

New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders

New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders

Effects of the herbal preparation STW 5-II on in vitro muscle activity in the guinea pig stomach.

STW 5 is a combination of nine medicinal herbal extracts and used to treat functional gastrointestinal disorders including functional dyspepsia. It has a region-specific effect by relaxing the proximal and contracting the distal stomach. The research combination STW 5-II (Iberogast® Advance) lacks three herbal extracts but seems clinically as effective as STW 5. However, the action of STW 5-II on gastric motility is unknown. In vitro circular and longitudinal muscle tone and contractility were recorded from guinea pig gastric fundus and antrum with isometric force transducers. STW 5-II decreased concentration-dependently (64-512µg/ml) the tone of circular and longitudinal muscle strips from the fundus. In contrast, STW 5-II increased concentration-dependently contraction amplitude in antral circular and longitudinal muscle. The effects were region-dependent but comparable in the two muscle layers. Application of 512µg STW 5 or STW 5-II revealed comparable effects in the fundus and antrum circular and longitudinal muscle strips. STW 5-II had a region-specific effect and relaxed the proximal stomach but increased the contractility in the antrum. It was as effective as STW 5 which may explain its comparable clinical effects in treating functional dyspepsia. Impaired accommodation may be normalized through relaxation of the fundus, while the motility-promoting effects leading to an increase in antral motility may activate the gastric pump.

Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging.

Vagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the effects of different VNS parameters and polarity on postprandial gastric motility remain incompletely characterized. In anesthetized rats (N=3), we applied monophasic electrical stimuli to the left cervical vagus and recorded compound nerve action potential (CNAP) as a measure of nerve response. We evaluated to what extent afferent or efferent pathway could be selectively activated by monophasic VNS. In a different group of rats (N=13), we fed each rat a gadolinium-labeled meal and scanned the rat stomach with oral contrast-enhanced magnetic resonance imaging (MRI) while the rat was anesthetized. We evaluated the antral and pyloric motility as a function of pulse amplitude (0.13, 0.25, 0.5, 1mA), width (0.13, 0.25, 0.5ms), frequency (5, 10Hz), and polarity of VNS. Monophasic VNS activated efferent and afferent pathways with about 67% and 82% selectivity, respectively. Primarily afferent VNS increased antral motility across a wide range of parameters. Primarily efferent VNS induced a significant decrease in antral motility as the stimulus intensity increased (R=-.93, P<.05 for 5Hz, R=-.85, P<.05 for 10Hz). The VNS with either polarity tended to promote pyloric motility to a greater extent given increasing stimulus intensity. Monophasic VNS biased toward the afferent pathway is potentially more effective for facilitating occlusive contractions than that biased toward the efferent pathway.

SPARC: Transcutaneous Auricular Vagal Nerve Stimulation Increases Antroduodenal Motility in Rat within a Narrow Range of Stimulus Parameters

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising, non‐invasive approach to modulate activity in the central nervous system, heart, lungs, stomach and other organs that receive projections from the vagus nerve. The optimal stimulus parameters for modulating stomach function are unknown, preventing further development of taVNS as a device‐based treatment for motility disorders like gastroparesis. We hypothesized that taVNS parameters could be tuned to preferentially modulate antroduodenal motility with fewer off‐target effects on the heart than cervical VNS. Using a custom‐made stimulation and recording system (Autonomous Neural Control, or ANC), we surveyed the taVNS‐mediated effects on cardiac, vagal (ventral gastric branch), antral and duodenal motility in male Sprague Dawley rats under isoflurane anesthesia (250–400 g; N = 14 rats). With custom carbon gel electrodes, we stimulated the left cymba concha at 1 or 10 Hz using 28 combinations of stimulus pulse currents and durations (0, 0.2, 0.4, 0.6, 0.8, 1.0 and 1.2 mA pulse currents in combination with 0.1, 0.2, 0.4 and 0.8 ms pulse durations), while measuring the electrocardiogram, antral electrogastrogram, and antral/duodenal motility with implanted strain gauges. The ANC software applied each stimulus parameter combination in a random order in 60 s cycles (20 s ON/40 s OFF). Stimulus pulse durations less than 0.4 ms were not associated with any significant effects on cardiac (measured from the electrocardiogram) or gastric activity (measured from the antral electrogastrogram as well as antral and duodenal strain gauge recordings), but did produce notable increases in nerve activity at the level of the ventral gastric branch (measured with an implanted bipolar cuff electrode). A pulse duration of 0.8 ms produced the most robust and consistent decrease in heart rate, increase in heart rate variability, increase in antral smooth muscle activity, and increase in antroduodenal motility, as is expected from an increase in vagal outflow. In contrast to cervical VNS, where the optimal parameters for increasing antral motility largely overlapped with those that induced severe bradycardia, the optimal taVNS parameters that increased antroduodenal motility at 1 or 10 Hz (Pulse Current: 0.2–0.6 mA | Pulse Duration: 0.4–0.8 ms) required less current, on average, than the stimulus parameters that produced the greatest reduction in heart rate and increase in heart rate variability (Pulse Current: 0.4–1.0 mA | Pulse Duration: 0.4–0.8 ms). Pulse currents greater than 0.6 mA did not have any significant effect on antroduodenal motility, supporting the value of our parameter search approach in sorting the useful from the useless stimulus parameters. These results strongly support taVNS as a viable approach to modulate gastrointestinal activity with greater specificity and control over stomach function than cervical VNS.Support or Funding InformationThis work was supported by NIH SPARC OT2 OD023847