Gastric Contractility Research Articles

Postprandial effect of gastrointestinal hormones and gastric activity in patients with irritable bowel syndrome

Altered gut regulation, including motor and secretory mechanisms, is characteristic of irritable bowel syndrome (IBS). The severity of postprandial symptoms in IBS patients is associated with discomfort and pain; gas-related symptoms such as bloating and abdominal distension; and abnormal colonic motility. The aim of this study was to assess the postprandial response, i.e., gut peptide secretion and gastric myoelectric activity, in patients with constipation-predominant IBS. The study was conducted on 42 IBS patients (14 males, 28 females, mean age 45.1 ± 15.3 years) and 42 healthy participants (16 males, 26 females, mean age 41.1 ± 8.7 years). The study assessed plasma gut peptide levels (gastrin, CCK—Cholecystokinin, VIP—Vasoactive Intestinal Peptide, ghrelin, insulin) and gastric myoelectric activity obtained from electrogastrography (EGG) in the preprandial and postprandial period (meal–oral nutritional supplement 300 kcal/300 ml). Mean preprandial gastrin and insulin levels were significantly elevated in IBS patients compared to the control group (gastrin: 72.27 ± 26.89 vs. 12.27 ± 4.91 pg/ml; p < 0.00001 and insulin: 15.31 ± 12.92 vs. 8.04 ± 3.21 IU/ml; p = 0.0001), while VIP and ghrelin levels were decreased in IBS patients (VIP: 6.69 ± 4.68 vs. 27.26 ± 21.51 ng/ml; p = 0.0001 and ghrelin: 176.01 ± 88.47 vs. 250.24 ± 84.55 pg/ml; p < 0.0001). A nonsignificant change in the CCK level was observed. IBS patients showed significant changes in postprandial hormone levels compared to the preprandial state—specifically, there were increases in gastrin (p = 0.000), CCK (p < 0.0001), VIP (p < 0.0001), ghrelin (p = 0.000) and insulin (p < 0.0001). Patients with IBS showed reduced preprandial and postprandial normogastria (59.8 ± 22.0 vs. 66.3 ± 20.2%) compared to control values (83.19 ± 16.7%; p < 0.0001 vs. 86.1 ± 9.4%; p < 0.0001). In response to the meal, we did not observe an increase in the percentage of normogastria or the average percentage slow-wave coupling (APSWC) in IBS patients. The postprandial to preprandial power ratio (PR) indicates alterations in gastric contractions; in controls, PR = 2.7, whereas in IBS patients, PR = 1.7, which was significantly lower (p = 0.00009). This ratio reflects a decrease in gastric contractility. Disturbances in the postprandial concentration of gut peptides (gastrin, insulin and ghrelin) in plasma may contribute to abnormal gastric function and consequently intestinal motility, which are manifested in the intensification of clinical symptoms, such as visceral hypersensitivity or irregular bowel movements in IBS patients.

Peripheral administration of neuropeptide W inhibits gastric emptying in rats: The role of small diameter afferent fibers and cholecystokinin receptors

Neuropeptide W (NPW), a novel hypothalamic peptide, contributes to the central regulation of food intake and energy balance, and suppresses feeding behavior when administered centrally. The aim of our study was to investigate the role of peripherally administered NPW in the modulation of gastric emptying, and to evaluate the participation of afferent fibers, cholecystokinin (CCK) receptors and gastric smooth muscle contractility in the regulatory effects of NPW on gastric motility. In Sprague-Dawley male rats equipped with gastric fistula, gastric emptying rate of the saline and peptone solutions was measured following subcutaneous administration of NPW (0.1 or 5 μg/kg) preceded by subcutaneous injections of saline, CCK-1 or CCK-2 receptor antagonists. Another group of rats with cannulas were injected subcutaneously with capsaicin for afferent denervation before commencing emptying trials. The effect of NPW on carbachol-induced gastric contractility and the role of CCK receptors in gastric smooth muscle contractility were also assessed in gastric strips. Peripheral injection of NPW delayed gastric emptying rate of both caloric and non-caloric liquid test meals, while administration of CCK-1 or CCK-2 receptor antagonists or denervation of small diameter afferents reversed NPW–induced delay in gastric emptying. Moreover, NPW inhibited antrum contractility in the organ bath. Our results revealed that peripherally administered NPW delayed liquid emptying from the stomach via the involvement of small diameter afferent neurons and CCK receptors, and thereby this regulatory role may contribute to its central regulatory role in controlling food intake and energy balance.

Motor Dysfunction of Gastric Antral Smooth Muscle in Diabetic Rats: Contribution of ATP-Dependent Potassium Channels.

The goal of the current research was to further elucidate the role of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in the motility and contractility force of gastric smooth muscle of diabetic rats. Male Wistar rats (190-230 g) were grouped into control and streptozotocin (STZ)-induced diabetes (55 mg/kg) rats. Thirty days later, gastric muscle contractility was measured using a myograph and a force transducer of antral segments immersed in a tissue bath. Gastric emptying response was measured through feeding of standard pellet. Furthermore, the expression of KATP channel subunits in antral smooth muscle was determined by western blot technique. The amplitude of KCl-evoked twitch contractions of diabetic antral strips was about 25% more than control (P < 0.05). Application of minoxidil, a KATP channel opener, dose dependently decreased the force of twitch contractions in both normal and diabetic antral strips. Application of 10 μM glibenclamide, a KATP channel blocker, did not antagonize the minoxidil-induced relaxation of antral strips. Diabetic gastric emptying was faster than normal, although not significant. Despite the relaxant effect of minoxidil on gastric emptying rate in normal rats (P < 0.05), this effect was not observed in diabetic rats. Also, glibenclamide increased gastric emptying and antagonized minoxidil-induced relaxation in normal rats (P < 0.05). Furthermore, the expression of KATP Kir6.1 and SUR2B subunits was substantially reduced in antral smooth muscle in diabetic condition (P < 0.01). These results propose that KATP channels may contribute to the development of gastric motility disorders in diabetes.

BMSCs Promote Differentiation of Enteric Neural Precursor Cells to Maintain Neuronal Homeostasis in Mice With Enteric Nerve Injury

Our previous study showed that transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) promoted functional enteric nerve regeneration in denervated mice but not through direct transdifferentiation. Homeostasis of the adult enteric nervous system (ENS) is maintained by enteric neural precursor cells (ENPCs). Whether ENPCs are a source of regenerated nerves in denervated mice remains unknown. Genetically engineered mice were used as recipients, and ENPCs were traced during enteric nerve regeneration. The mice were treated with benzalkonium chloride to establish a denervation model and then transplanted with BMSCs 3 days later. After 28 days, the gastric motility and ENS regeneration were analyzed. The interaction between BMSCs and ENPCs invitro was further assessed. Twenty-eight days after transplantation, gastric motility recovery (gastric emptying capacity, P < .01; gastric contractility, P < .01) and ENS regeneration (neurons, P < .01; glial cells, P < .001) were promoted in BMSCs transplantation groups compared with non-transplanted groups in denervated mice. More importantly, we found that ENPCs could differentiate into enteric neurons and glial cells in denervated mice after BMSCs transplantation, and the proportion of Nestin+/Ngfr+ cells differentiated into neurons was significantly higher than that of Nestin+ cells. A small number of BMSCs located in the myenteric plexus differentiated into glial cells. Invitro, glial cell-derived neurotrophic factor (GDNF) from BMSCs promotes the migration, proliferation, and differentiation of ENPCs. In the case of enteric nerve injury, ENPCs can differentiate into enteric neurons and glial cells to promote ENS repair and gastric motility recovery after BMSCs transplantation. BMSCs expressing GDNF enhance the migration, proliferation, and differentiation of ENPCs.

GASTROINTESTINAL MOTILITY IN ELDERLY PATIENTS WITH WELL-CONTROLLED TYPE 2 DIABETES MELLITUS.

Gastrointestinal (GI) motility disorders in type 2 diabetes mellitus (T2DM) are common. However, the endpoints in well-controlled T2DM in elderly patients are barely understood. To evaluate GI transit and gastric myoelectric activity in elderly patients with T2DM who were undergoing treatment with metformin and to compare them with non-diabetic healthy controls. A total of thirty participants were enrolled in this study: young non-diabetic (n=10), elderly non-diabetic controls (n=10), and patients with T2DM managed with metformin (n=10). After fasting overnight, the participants ingested a standard meal and magnetic markers for non-invasive monitoring of GI transit and gastric contractility using the alternating current biosusceptometry and electrogastrography techniques. Mean gastric emptying time, mean colon arrival time, and mean intestinal transit time were determined. There were no significant differences between the groups and in the parameters evaluated (P>0.05). The frequency and amplitude of gastric myoelectric activity were not different between groups; however, abnormal rhythmic index and the half-bandwidth were slightly higher for both elderly diabetic and non-diabetic groups compared with the young adults (P<0.01 and P<0.05, respectively). Our study showed unaltered gastric emptying and intestinal transit in T2DM patients with good glycemic control, and suggest changes in the gastric electrical activity can be a part of aging.

Ameliorative Effects of Humulus japonicus Extract and Polysaccharide-Rich Extract of Phragmites rhizoma in Rats with Gastrointestinal Dysfunctions Induced by Water Avoidance Stress.

Chronic stress can cause the gastrointestinal disorders characterized by an altered bowel movement and abdominal pain. Studies have shown that Humulus japonicus extract (HJE) has anti-inflammatory and antidiarrheal effects, and Phragmites rhizoma extract (PEP) has antioxidative and antistress effects. The present study aimed to investigate the possible effects of HJE and PEP in rat models with stress-induced gastrointestinal dysfunctions. The rats were exposed to water avoidance stress (WAS, 1 h/day) for 10 days to induce gastrointestinal disorders. We found that WAS significantly increased fecal pellet output during 1 h stress, gastric emptying, colonic contractility, and permeability compared to the normal rats. Pretreatment with HJE and PEP (0.25 and 0.5 mL/kg, both administered separately) improved the increased gastric emptying and colonic contractility induced by electrical field stimulation, acetylcholine, and serotonin and also alleviated the increased colonic permeability. HJE and PEP also increased the claudin-1 and occludin expressions, reduced by WAS. WAS increased the concentration of TNF-α and TBARS and reduced FRAP. HJE and PEP recovered these effects. HJE and PEP improved the gastrointestinal disorders induced by WAS by upregulating the tight junction protein, possibly acting on cholinergic and serotonergic receptors to abolish the colonic hypercontractility and hyperpermeability and degradation of inflammatory cytokines via an antioxidant effect.

S1440 Novel Neuromodulation Treatment Using Repetitive Magnetic Stimulation for Diabetic Gastroparesis: Preliminary Results From a Proof-of-Concept Study

Introduction: Diabetic gastroparesis (DGp) is chartacterized by autonomic neuropathy, for which there are limited effective treatments. Stimulation of thoracic sympathetic and parasympathetic nerves may improve symptoms in patients with diabetic gastroparesis by enhancing gastric contractility. Our aim was to assess safety and feasibility of a novel, non-invasive treatment, Thoracic Splanchnic Magnetic Neuromodulation Therapy (ThorS-MagNT,) for refractory DGp in a proof-of-concept study. Methods: DGp patients, who required hospital admission and without known GI mucosal disease, were included. A mapping procedure in the left and right posterior mid-thoracic regions, using a single-pulse circular 90 mm coil (MAGSTIM, Whitland, UK) determined the location and minimum intensity required to achieve a motor evoked response (MEP) of 10 µV with 50% of trials (resting motor threshold) in the upper rectus abdominis and external oblique muscles. ThorS-MagNT was administered at 50% intensity above motor threshold, using a 70 mm double air film self-cooling coil (MAGSTIM Rapid2) positioned over bilateral pre-determined locations to deliver a total of 1200 stimulations at 1 Hz. Treatments were administered twice daily for five consecutive days. Safety and tolerability data were collected. ANMS GCSI-DD was assessed at baseline and throughout the treatment period. Patients who completed all ten treatments were defined as per protocol. Results: Seven DGp patients (6F; 1M) were enrolled . All subjects tolerated administered treatment sessions. One DGp patient experienced medication-related hypotension-a serious adverse event unrelated to study treatment. After resuscitation and missing one treatment, this subject completed 4 subsequent treatments. One patient reported self-limited tingling and numbness, which resolved after treatment. No other adverse events occurred. In four per protocol subjects, an average of 68.25% reduction in ANMS GCSI-DD score from baseline was observed (Table 1). Two other subjects had an average of 13.95% reduction in ANMS GCSI-DD and one study subject dropped out. Conclusion: ThorS-MagNT appears to be feasible, safe and a promising novel treatment for refractory DGp. Further studies are needed in larger samples to assess its effects on symptoms, hospitalization duration, gastric emptying and safety. Acknowledgement: Supported by the NIDDK Diabetic Complications Consortium grants DK076169 & DK115255.Table 1.: ANMS GCSI-DD scores at baseline versus during treatment.

Effect of obesity on gastrointestinal transit, pressure and pH using a wireless motility capsule

BackgroundDespite the increasing prevalence and medical burden of obesity, the understanding of gastrointestinal physiology in obesity is scarce, which hampers drug development. AimTo investigate the effect of obesity and food intake on gastrointestinal transit, pressure and pH. Material and methodsAn exploratory cross-sectional study using a wireless motility capsule (SmartPill©) was performed in 11 participants with obesity and 11 age- and gender-matched participants with normal weight (group) in fasted and fed state (visit). During the first visit, the capsule was ingested after an overnight fast. During a second visit, the capsule was ingested after a nutritional drink to simulate fed state. Linear mixed models were constructed to compare segmental gastrointestinal transit, pressure and pH between groups (obesity or control) and within every group (fasted or fed). ResultsFood intake slowed gastric emptying in both groups (both P < 0.0001), though food-induced gastric contractility was higher in participants with obesity compared to controls (P = 0.02). In the small intestine, a higher contractility (P = 0.001), shorter transit (P = 0.04) and lower median pH (P = 0.002) was observed in participants with obesity compared to controls. No differences were observed for colonic measurements. ConclusionObesity has a profound impact on gastrointestinal physiology, which should be taken into account for drug development.

High-fat Diet Enhances Gastric Contractility, but Abolishes Nesfatin-1-induced Inhibition of Gastric Emptying.

Background/AimsGastrointestinal motility changes contribute to development and maintenance of obesity. Nesfatin-1 (NES-1) is involved in central appetite control. The aim is to elucidate effects of NES-1 and high-fat diet (HFD) on gastrointestinal motility and to explore myenteric neuron expressions of tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP), and neuronal nitric oxide synthase (nNOS) in HFD-induced oxidative injury.MethodsSprague-Dawley rats were fed with normal diet (ND) or HFD. Gastric emptying rate was measured following NES-1 (5 pmol/rat, intracerebroventricular) preceded by subcutaneous injections of glucagon-like peptide 1 (GLP-1), cholecystokinin 1 (CCK-1), and gastrin/CCK-2 receptor antagonists. In carbachol-contracted gastric and ileal strips, contractile changes were recorded by adding NES-1 (0.3 nmol/L), GLP-1, CCK-1, and gastrin/CCK-2 antagonists.ResultsNeither HFD nor NES-1 changed methylcellulose emptying, but NES-1 delayed saline emptying in cannulated ND-rats. Inhibitory effect of NES-1 on gastric emptying in ND-rats was reversed by all antagonists, and abolished in HFD-rats. In HFD-rats, carbachol-induced contractility was enhanced in gastric, but inhibited in ileal strips. HFD increased body weight, while serum triglycerides, alanine transaminase, aspartate aminotransferase, glucose, and levels of malondialdehyde, glutathione, myeloperoxidase activity, and luminol-chemiluminescence in hepatic, ileal, and adipose tissues were similar in ND- and HFD-rats, but only lucigenin-chemiluminescence was increased in HFD-rats. Vasoactive intestinal peptide (VIP) and TH immunoreactivities were depressed and nNOS immunoreactivity was increased in gastric tissues of HFD-rats, while VIP and TH were enhanced, but nNOS was reduced in their intestines.ConclusionsHFD caused mild systemic inflammation, disrupted enteric innervation, enhanced gastric contractility, inhibited ileal contractility, and eliminated inhibitory effect of NES-1 on gastric motility.

Gastric accumulation of enteral nutrition reduces pressure changes induced by phasic contractility in an isovolumetric intragastric balloon.

An isovolumetric intragastric balloon to continuously measure gastric phasic contractility was recently developed by us. We aimed to investigate the readout of this technique in relation to gastric content and gastric emptying. In this crossover investigation, the VIPUNTM Gastric Monitoring System, which comprises a double lumen nasogastric feeding tube with integrated intragastric balloon, was used to assess phasic gastric contractility by interpretation of the pressure in an isovolumetric balloon in 10 healthy subjects. Balloon pressure was recorded in fasted state, during a 2-hour intragastric nutrient infusion (1kcal/ml at 25, 75, or 250ml/h) and 4hours post-infusion, and quantified as Gastric Balloon Motility Index (GBMI), ranging from 0 (no contractility) to 1 (maximal contractility). Gastric accumulation was quantified with magnetic resonance imaging and gastric emptying with a13 C-breath test. Results are expressed as mean(SD). GBMI was significantly lower during infusion at 250ml/h compared to baseline (0.13(0.05) versus 0.46(0.12)) and compared to infusion at 25 (0.54(0.21)) and 75ml/h (0.43(0.20)), all P<0.005. Gastric content volume was larger after infusion at 250 versus 75ml/h (P<0.001). Half-emptying time and accumulation were both negatively correlated with postprandial contractility. Postprandial GBMI was significantly lower when GCV>0ml compared to when the stomach was empty. Enteral nutrition dose-dependently decreased the contractility readout. This decrease was linked to gastric accumulation of enteral nutrition.

Direct optogenetic stimulation of smooth muscle cells to control gastric contractility

Rationale: Antral peristalsis is responsible for gastric emptying. Its failure is called gastroparesis and often caused by dysfunction of enteric neurons and interstitial cells of Cajal (ICC). Current treatment options, including gastric electrical stimulation, are non-satisfying and may improve symptoms but commonly fail to restore gastric emptying. Herein, we explore direct optogenetic stimulation of smooth muscle cells (SMC) via the light-gated non-selective cation channel Channelrhodopsin2 (ChR2) to control gastric motor function.Methods: We used a transgenic mouse model expressing ChR2 in fusion with eYFP under the control of the chicken-β-actin promoter. We performed patch clamp experiments to quantify light-induced currents in isolated SMC, Ca2+ imaging and isometric force measurements of antral smooth muscle strips as well as pressure recordings of intact stomachs to evaluate contractile responses. Light-induced propulsion of gastric contents from the isolated stomach preparation was quantified in video recordings. We furthermore tested optogenetic stimulation in a gastroparesis model induced by neuronal- and ICC-specific damage through methylene blue photo-toxicity.Results: In the stomachs, eYFP signals were restricted to SMC in which blue light (460 nm) induced inward currents typical for ChR2. These depolarizing currents led to contractions in antral smooth muscle strips that were stronger than those triggered by supramaximal electrical field stimulation and comparable to those evoked by global depolarization with high K+ concentration. In the intact stomach, panoramic illumination efficiently increased intragastric pressure achieving 239±46% (n=6) of the pressure induced by electrical field stimulation and triggered gastric transport. Within the gastroparesis model, electric field stimulation completely failed but light still efficiently generated pressure waves.Conclusions: We demonstrate direct optogenetic stimulation of SMC to control gastric contractility. This completely new approach could allow for the restoration of motility in gastroparesis in the future.

Gastrointestinal Side Effects of Triple Immunosuppressive Therapy Evaluated by AC Biosusceptometry and Electrogastrography in Rats.

Triple immunosuppressive therapy is associated with several gastrointestinal disorders. The aim of this study was to investigate the effects induced by the triple immunosuppressive therapy on the gastrointestinal tract of rats. Male Wistar rats were randomly assigned into three experimental groups: Control: filtered water; TAC + MPS + PRED: treated with Tacrolimus plus Mycophenolate Sodium plus Prednisone; and CSA + AZA + PRED: treated with Cyclosporine plus Azathioprine plus Prednisone. The treatment was done for 14 days by gavage. Gastric emptying and contractility were evaluated by the Alternating Current Biosusceptometry (ACB) and Electrogastrography (EGG). Histological, biochemical and hematological analyses were also performed. Gastric emptying time was slower in the CSA + AZA + PRED group in comparison with control (p<0.01) and TAC + MPS + PRED groups (p<0.001). Animals treated with TAC + MPS + PRED showed accelerated gastric emptying (p<0.05) compared to control. The amplitude of gastric contractions in both immunosuppressed groups was higher than observed in the control. The frequency of gastric contractions for the CSA + AZA + PRED group was also increased (p<0.01). Results obtained by EGG were similar to those recorded with the ACB. The thickness of the circular layer from stomach muscle decreased in both immunosuppressed groups, while the longitudinal layer was reduced only in the CSA + AZA + PRED group. Triple immunosuppressive therapy alters gastric motility, compromises the muscular layers and the association between CSA, AZA, and PRED provokes the major alterations in the structure and gastric function. Specific gastrointestinal side effects resulting from different immunosuppressive therapies still need to be elucidated in order to provide more effective and personalized therapy for patients.

Erythromycin stimulates phasic gastric contractility as assessed with an isovolumetric intragastric balloon pressure measurement.

A novel technique to assess gastric motility by measuring the pressure in a low-volume intragastric balloon was developed to monitor (disordered) motility. We previously showed that this technique allows measuring pharmacologically induced inhibition of motility. In this study, we assessed whether it is possible to measure pharmacologically induced stimulation of gastric motility using 200mg erythromycin. Erythromycin is a highly effective stimulator of gastric emptying and contractility. After an overnight fast, a nasogastric balloon catheter was introduced in healthy subjects. After inflation with 120ml of air, the catheter was connected to a pressure sensor. Intraballoon pressure was continuously recorded for 4h. After a baseline recording of 2h, 200mg erythromycin was infused intravenously over 20min while the recording continued for 2h. Epigastric symptoms were surveyed on 100-mm visual analogue scales. Motility was quantified from the pressure recording as a gastric balloon motility index. Wilcoxon signed-rank tests were performed. Data are shown as median (interquartile range). Six subjects were enrolled and five completed the procedures (age: 28 (25-29) years, body mass index: 24.0 (23.8-24.5) kgm-2 ). One subject could not tolerate tube placement. Bloating, nausea, and epigastric sensation scores were 0 (0-3), 0 (0-1), and 1 (0-1) mm, respectively. Erythromycin significantly increased the motility index from 0.48 (0.41-0.51) to 0.79 (0.70-0.82) (p=0.03). Gastric motility assessed via pressure measurement in a low-volume intragastric balloon is able to detect pharmacologically stimulated motility in healthy subjects, which further validates this technique.

Baseline Predictors of Longitudinal Changes in Symptom Severity and Quality of Life in Patients With Suspected Gastroparesis

Whether gastric emptying tests predict longitudinal outcomes in patients with symptoms of gastroparesis is unclear. We aimed to determine whether baseline gastric emptying tests and gut motility parameters could impact longitudinal symptom(s) and quality of life (QOL) in a prospective, observational cohort study of patients with symptoms of gastroparesis. One hundred fifty patients with gastroparesis symptoms underwent simultaneous scintigraphy (GES) and wireless motility capsule (WMC) measurement of gastric emptying and other motility parameters. Patient Assessment of Upper Gastrointestinal Symptoms and Quality of Life were administered at baseline, and 3 and 6 months after testing. Multivariable generalized linear marginal models were fit to determine which baseline parameters predict longitudinal changes in symptoms and QOL. Overall upper GI symptoms and QOL scores were moderate in severity at baseline and significantly improved over 6 months. Clinical variables, including female gender, harder stools by Bristol stool form score, and presence of functional dyspepsia (FD) by Rome III criteria, were predictive of more severe upper GI symptoms. Even after controlling for these clinical factors, delayed gastric emptying by GES or WMC was associated with worse symptom severity and QOL scores. Low gastric and elevated small bowel contractile parameters by WMC were also independently associated with more severe upper GI symptoms and worse QOL scores. Baseline features, including demographic and clinical variables, delayed gastric emptying and abnormal gastrointestinal contractility, were independent predictors of more severe longitudinal symptoms and worse quality of life outcomes. These factors may help to risk stratify patients and guide treatment decisions. ClinicalTrials.gov no: NCT02022826.

A Botanical-Based Equine Nutraceutical Reduces Gastric Smooth Muscle Contractile Force In Vitro

The objective of this study was to evaluate the effect of a botanical-based equine nutraceutical on contractility of gastric smooth muscle in vitro. Gastric ulcers are prevalent in performance horses and negatively impact horse welfare. Gastric hypermotility has been positively associated with the development of gastric ulceration in nonequine species, and reduction of hypermotility may be protective against their development. Stomachs from 12 pigs processed for food at a provincially inspected abattoir were collected within 1 hour of slaughter. Explants of nonglandular gastric tissue were prepared and suspended in a tissue bath, attached to a force transducer, in the presence or absence of a simulated digest extract of the nutraceutical. Tissue was stimulated to contract using increasing doses of acetylcholine. Peak and mean contractile force over 1 and 2 minutes after exposure to acetylcholine were measured. Exposure of gastric smooth muscle to the nutraceutical significantly reduced contractility of the tissue. These data provide support for the use of this nutraceutical to reduce contractility of nonglandular gastric smooth muscle and may indicate a protective effect of this nutraceutical in horses with mechanically induced gastric ulcers. Future studies are needed to clarify the role of gastric hypermotility on development of equine gastric ulcers and to determine the effect of this nutraceutical on equine gastric contractility and ulcerogenesis in vivo.

Burn-Induced Impairment of Ileal Muscle Contractility Is Associated with Increased Extracellular Matrix Components

IntroductionSevere burns lead to marked impairment of gastrointestinal motility, such as delayed gastric emptying and small and large intestinal ileus. However, the cellular mechanism of these pathologic changes remains largely unknown. MethodsMale Sprague Dawley rats approximately 3 months old and weighing 300–350 g were randomized to either a 60% total body surface area full-thickness scald burn or sham procedure and were sacrificed 24 h after the procedure. Gastric emptying, gastric antrum contractility ileal smooth muscle contractility, and colonic contractility were measured. Muscularis externa was isolated from the ileal segment to prepare smooth muscle protein extracts for Western blot analysis. ResultsCompared with sham controls, the baseline rhythmic contractile activities of the antral, ileal, and colonic smooth muscle strips were impaired in the burned rats. Simultaneously, our data showed that ileal muscularis ECM proteins fibronectin and laminin were significantly up-regulated in burned rats compared with sham rats. TGF-β signaling is an important stimulating factor for ECM protein expression. Our results revealed that TGF-β signaling was activated in the ileal muscle of burned rats evidenced by the activation of Smad2/3 expression and phosphorylation. In addition, the total and phosphorylated AKT, which is an important downstream factor of ECM signaling in smooth muscle cells, was also up-regulated in burned rats’ ileal muscle. Notably, these changes were not seen in the colonic or gastric tissues. ConclusionDeposition of fibrosis-related proteins after severe burn is contributors to decreased small intestinal motility.

Electroacupuncture Against Ethanol-Induced Gastric Ulcer in Rats: Effects on Gastric Contractility and in the Levels of TNF-α

To correlate the effects of the Electroacupuncture (EA) with the levels of TNF-I± and the gastric contractility in both ulcerated and non-ulcerated control rats...

The sphingosine analog fingolimod (FTY720) enhances tone and contractility of rat gastric fundus smooth muscle.

Sphingosine and its metabolite sphingosine phosphate (S1P) regulate a multitude of biological functions, including the contractile state of smooth. Gastrointestinal side effects have been reported in patients treated with FTY720, a sphingosine analog that is approved for the treatment of multiple sclerosis. The aim of this study was to characterize the effects of FTY720 on rat gastric fundus smooth muscle under basal conditions and during activation induced by high-K+ solution. Isometric contractions of isolated circular strips of gastric fundus smooth muscle were recorded using the organ bath method. The effects of FTY720 or vehicle were recorded under control conditions and in the presence of indomethacin, L-NAME, HA-1100, nifedipine, JTE-013, and suramin. Tone and contractions recorded in the presence of FTY720 or vehicle are reported as % of the amplitude of an initial high-K+ contraction obtained under control conditions. From a concentration of 10μmol L-1 onwards, FTY720 increased the tone, reaching 8.9%±7.5% at 100μmol L-1 (P<.05). With indomethacin in the solution, the effects of FTY720 were enhanced (32.1%±7.7%; P<.001). The FTY720-induced increase in tone was abolished in the absence of extracellular Ca2+ and reduced by nifedipine, HA-1100, JTE-013, and suramin. Furthermore, FTY720 increased high-K+ contractions in the presence of indomethacin. FTY720 increases tone and contractile responses to depolarization in gastric fundus smooth muscle by triggering calcium entry and calcium sensitization in a S1P receptor-dependent manner. Taken together, the experimental results presented in this work suggest that FTY720 may increase gastric tone and contractility in patients.

Gastric Contractility Modulation - a novel method for the treatment of type 2 diabetes mellitus and obesity.

Because the majority of antidiabetic medications are of limited efficacy and patient compliance with treatment is usually poor, new therapies are still being searched for. In the review a newly developed system for treatment of subjects with type 2 diabetes and concomitant overweight/obesity is described. The system consists of an implantable pulse generator that delivers electrical stimuli through leads implanted in the sero-muscular layer of the stomach. The device recognises and automatically modulates natural electrical activity of the stomach during meals, strengthening gastric contractility. This increase in the force of contractions enhances vagal afferent activity. Modulated signals are transmitted to the regulatory centres in the brain in order to provoke an early response of the gut typical of a full meal. Clinical trials performed to date show that the system improves glycaemic control with minimal patient compliance needed and with added benefits of body weight loss, a decrease in blood pressure, and favourable changes in the lipid profile. The system is safe, well-tolerated, with a low risk of hypoglycaemia, and will probably become an alternative to the use of incretins or to bariatric surgery in obese patients who are unwilling to undergo a major and anatomically irreversible operation.

Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis.

Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P≤.02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P≤.04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P≤.03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P=.03). Diarrhea scores were higher with delayed SBTT and CTT (P≤.04). Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.