Effect of electrical stimulation on gastric electrical activity,motility and emptying

Abstract The aim was to measure the effect of gastric electrical stimulation on the frequency of canine antral pacesetter potentials (PPs), the strength of antral contractions, and the rate of gastric emptying while fasting, after feeding and with pentagastrin stimulation. Four conscious dogs with a stimulating electrode placed 10 cm proximal to the pylorus and recording electrodes and strain gauges placed 7, 5 and 3 cm proximal to the pylorus underwent myoelectric and strain gauge recordings while fasting, after feeding (250 ml 5% dextrose labelled with polyethylene glycol), and during pentagastrin infusion (0.5 μg kg^?1 min^?1) on four separate days. On each day, electrical stimulation was done using one of four stimulation frequencies (0, 6, 30 and 1200 stimuli per minute ***[s.p.m.]). Stimulation at 6 and 30 s.p.m. increased the fasting and fed PP frequency, whereas 1200 s.p.m. stimulation did not. Feeding decreased the maximum driven frequency, and pentagastrin increased it. Neither the motility index nor the gastric emptying rate were consistently changed by stimulation at any frequency. In conclusion, canine proximal antral stimulation at 6 and 30 s.p.m. sped PP frequency during fasting and after feeding, but stimulation over a wide range of frequencies had little effect on gastric contractions and emptying.     

The effect of Taraxacum officinale on gastric emptying and smooth muscle motility in Rodents

Background Taraxacum officinale (TO) is a traditional herbal medicine that has been widely used for abdominal illnesses. However, the efficacy and the mechanism of TO on gastric emptying (GE) and smooth muscle motility are unknown. Methods Ethyl acetate fraction (EA), n‐butanol fraction (BF), and aqueous fraction (AF) were prepared in succession from 70% ethanol extract (EE) of TO using solvent polarity chromatography. Phenol red meal was adopted to estimate GE in mice. A polygraph was used to measure the smooth muscle motility in rats. Key Results The percentage of GE was 48.8 ± 6.1% (vehicle control), 75.3 ± 6.5% (cisapride positive control), 68.0 ± 6.7% (EE), 53.3 ± 6.0% (EA), 54.1 ± 6.3% (AF), and 86.0 ± 6.5% (BF). Thus, BF was determined to be most effective in accelerating GE. This stimulatory effect of BF on GE was also supported by the observation that BF increased spontaneous contraction of gastric fundus and antrum and decreased the spontaneous motility of pyloric sphincter in vitro. Atropine blocked the stimulatory effect of BF on GE, whereas phentolamine and propranolol had no effect. Conclusions & Inferences BF seems to be a promising prokinetic agent. BF‐induced increase in the contraction of fundus and antrum contributes to an increase in the intra‐gastric pressure. BF‐induced decrease in the motility of pyloric sphincter contributes to a decrease in the resistance of food from the stomach to the small intestine. The acceleration of GE by BF is likely to be exerted through cholinergic stimulation.     

Gastric emptying in normal subjects: reproducibility and relationship to characteristics of the migrating motor complex

This study was designed to clarify whether a part of the variability in gastric emptying could be ascribed to a relationship between meal ingestion and phase activity of the migrating motor complex and whether reproducibility is increased when meal ingestion takes place in relation to preselected characteristics of the migrating motor complex. We examined 12 healthy males, and the design included three examinations, twice with meal ingestion in a duodenal Phase I, and once in a Phase II. The meal consisted of an omelette labelled with ^99mTc followed by 150 ml water labelled with ¹¹¹In. The results showed that liquid lag phase (min) and was significantly shorter in Phase II than in Phase I (1 vs. 4, P = 0.007). The half emptying time of solid linear phase (min) was reproduced with nearly identical median and range values in the three series (I[1]: 67[51–87]; I[2]: 63[47–80]; 61[47–76]). With meal ingestion in Phase I a significant difference between inter- and intra-individual variance could not be demonstrated. With meal ingestion in Phase I a second examination in Phase I did not increase reproducibility of any of the variables compared to a second examination in Phase II. In conclusion, scientific investigations on gastric emptying have to be performed with phase related meal ingestion and a double-radionuclide technique.     

Ghrelin does not stimulate gastrointestinal motility and gastric emptying: an experimental study of conscious dogs

Ghrelin is a peptide that was discovered in endocrine cells of the stomach. However, its action in regulating the fasted and fed motor activity of the digestive tract is not fully understood. In the present study, we examined the effects of an intravenous (i.v.) injection of canine ghrelin on the physiological fasted and fed motor activities in the stomach, duodenum, jejunum and colon of freely moving conscious dogs. An i.v. injection of canine ghrelin released growth hormone in a dose-dependent manner; however, it did not stimulate the motor activity of the digestive tract in either the fasted or the fed state. Moreover, an i.v. injection of high-dose canine ghrelin significantly reduced the motility index in the gastric body in the fasted state. Ghrelin did not accelerate gastric emptying, either. These results differ from previous reports dealing with rodents. It is significant that such results were obtained in research with dogs, which are larger animals.     

Delayed gastric emptying rates and impaired antral motility in children fulfilling Rome III criteria for functional abdominal pain

Background Gastric sensorymotor dysfunctions have been implicated in the pathophysiology of some functional gastrointestinal disorders, such as functional dyspepsia and irritable bowel syndrome. Therefore, we hypothesized that abnormal gastric emptying and impaired antral motility are possible underlying mechanisms of symptoms in children with functional abdominal pain (FAP). Methods Hundred and two children [37 (36.3%) males, 4–14 years, mean 7.8 years, SD 2.7 years] fulfilling Rome III criteria for FAP were recruited for this study. An age and sex compatible group of healthy children (n = 20) were selected as controls [8 (40%) males, 4–14 years, mean 8.4 years, SD 3.0 years]. Liquid gastric emptying rate (GER) and antral motility parameters (amplitude of antral contractions, frequency of antral contractions and antral motility index) were assessed using a previously reported ultrasound method. Key Results Average GER (42.1% vs 66.2% in controls), amplitude of antral contractions (56.5% vs 89%), frequency of contractions per 3 min (8.5 vs 9.3), and antral motility index (4.9 vs 8.3) were significantly lower in patients with FAP compared with controls (P < 0.01). Fasting antral area was higher in patients (1.4 vs 0.6, P < 0.0001). GER negatively correlated with the scores obtained for severity of abdominal pain (r = ?0.29, P = 0.004). Conclusions & Inferences Gastric emptying rate and antral motility parameters were significantly impaired in patients with FAP and GER negatively correlated with symptom severity. These findings highlight the possible role of gastrointestinal motility abnormalities in the pathophysiology of childhood FAP.     

The relationship between gastric pH and the emptying of solid, semisolid and liquid meals

The effect of three different meal constituents, solid, semisolid and liquid, on gastric pH, recorded in the proximal and distal stomach, was evaluated in a prospective study of 20 normal volunteers. The solid and liquid were ingested together as one meal and the semisolid as another. Simultaneous recordings of the rate of gastric emptying of the isotopically labelled meal constituents and the gastric pH were made. The rate of gastric emptying was more rapid for the liquid and semisolid constituents (t_1/2= 35.6, range 9.8–103.3 min and 47.4, range 33.5–120 min, respectively) than for the solid meal constituent (t_1/2= 72.0, range 45.0–103.8 min), P < 0.01. Both the combined meal of solid and liquid and the semisolid meal produced a higher pH response in the proximal stomach than in the distal stomach (5.2, range 2.4–6.1 vs 2.9, range 0.8–5.3 and 5.9, range 4.3–6.6 vs 4.3, range 1.1–5.9), P < 0.01. There were significant correlations between the rate of gastric emptying of all three meal constituents and the decline phase in the gastric pH recorded at both the proximal and distal probes, P < 0.01 (Pearson's correlation). The strongest correlations were found between the rate of gastric emptying and the gastric pH recorded in the proximal stomach. The decline phase of gastric pH followed the emptying of semisolid more closely than the emptying of either solid or liquid.     

Comparisons of the effects of enterostatin on food intake and gastric emptying in rats

The effects of central and peripheral administration of enterostatin (ENT) on food intake and gastric emptying of a non-nutrient liquid meal have been studied in rats. Intraperitoneal and intragastric administration of ENT at a dose of 120 nmol suppressed the intake of a high-fat diet but failed to inhibit gastric emptying in Sprague-Dawley (SD) rats. Intracerebroventricular (i.c.v.) ENT (1 nmol) reduced intake of a high-fat diet in Osborne-Mendel (OM) and SD rats but not in S5B/Pl rats, whereas it decreased gastric emptying in S5B/Pl and SD rats but not in OM rats. The data suggest that although central ENT may reduce gastric emptying rate, this effect is not related to the inhibitory effect of ENT on food intake.     

The migrating motor complex modulates intestinal motility response and rate of gastric emptying of caloric meals

Abstract The present study elucidates whether the phase of the migrating motor complex (MMC) present at the moment of food intake modulates postprandial motor response and rate of gastric emptying of caloric meals. Eight healthy male volunteers with a mean age of 26 years were examined twice. During water-perfused gastroduodenal manometry, a liquid meal with paracetamol added as a marker was orally administered during phase I and late phase II. Paracetamol appeared in serum 14.1 ± 3.8 min and 9.1 ± 4.0 (mean ± SD) min, respectively, after intake of the meal (P < 0.02). The area under the curve of s-paracetamol until 25 min after intake was 232 ± 169 μmoll_-1 min and 362 ± 130 (P < 0.05), respectively. When taken during late phase II, a phase III-like activity occurred within 2.1 ± 1.3 min in the duodenum, and was succeeded by quiescence. During phase I, the meal invariably initiated irregular contractions within 4 min. The phase of MMC during which a caloric meal is ingested modulates duodenal motor response and rate of gastric emptying during the initial postprandial period. Initial postprandial motor activity thus represents the combined effect of nutrient stimulation and the underlying enteric biorhythm as reflected by phase of MMC.     

Effects of cyclooxygenase-2 inhibitor on glucagon-induced delayed gastric emptying and gastric dysrhythmia in dogs

The objective of this study was to investigate the effects of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) on delayed gastric emptying and gastric dysrhythmia induced by glucagon. The study was performed in six healthy female dogs implanted with four pairs of gastric serosal electrodes, and a duodenal fistula for the assessment of gastric emptying. Each dog was studied in three randomized sessions: control, glucagon and COX-2 inhibitor (celecoxib). Gastric emptying was assessed every 15 min via a duodenal cannula by calculating the amount of collected phenol red which mixed with the test meal and gastric slow waves were recorded at the same time. We found that: (i) glucagon significantly and substantially decreased gastric emptying of liquids (P < 0.001, anova), increased blood glucose (BG) levels, and induced gastric dysrhythmias. The delayed gastric emptying was correlated with the BG level (R = -0.77, P < 0.001) and (ii) celecoxib improved glucagon-induced delayed gastric emptying at 30, 45, 60 and 75 min after feeding. Celecoxib did not blocked dysrhythmic action of glucagon (P > 0.05, anova). In conclusion, glucagon induces delayed gastric emptying partially via COX-2-derived prostaglandins. However, COX-2-derived prostaglandins are not involved in glucagon-evoked gastric dysrhythmia. Selective COX-2 inhibitors may provide a possible therapeutic option for diabetic gastroparesis.     

Influence of gastric acid on gastric emptying and gastric distension-induced pain response in rats - effects of famotidine and mosapride

Background Gastroduodenal acidification has been reported to aggravate upper abdominal discomfort and pain that are symptoms suffered by functional dyspepsia (FD) patients. Delayed gastric emptying and hypersensitivity to gastric distension (GD) contribute importantly to the pathophysiology of FD. Methods In the present study, we determined the influence of pentagastrin‐stimulated endogenous gastric acid on gastric emptying and GD‐induced pain responses using rat model systems. Moreover, we evaluated the effects of famotidine and mosapride on changes in gastric emptying and the GD‐induced pain response to gastric acid hypersecretion. Gastric emptying was measured by excretion of glass beads that had been intragastrically administered with a liquid nutrient, and gastric pain response was evaluated by observing whether a GD‐induced increase in mean blood pressure occurred. Key Results Pentagastrin (2 mg kg^?1, s.c.) which markedly and continuously stimulated gastric acid secretion, significantly delayed and enhanced respectively, gastric emptying and pain compared with saline‐injected groups. Oral famotidine (0.1–3 mg kg^?1) and mosapride (0.3–3 mg kg^?1) administration in a dose‐dependent manner accelerated the delay of gastric emptying. Furthermore, famotidine (0.3–3 mg kg^?1) significantly alleviated the aggravation of the GD‐induced pain response, but mosapride (10 mg kg^?1) did not. Conclusions & Inferences We established rat models to evaluate the effect of gastric acid hypersecretion on gastric emptying and the GD‐induced pain response. In these models, acid hypersecretion delayed gastric emptying and aggravated the pain response. Furthermore, we showed that famotidine ameliorated both delayed gastric emptying and gastric hypersensitivity, whereas mosapride only improved delayed gastric emptying.     

Therapeutic efficacy of acotiamide in patients with functional dyspepsia based on enhanced postprandial gastric accommodation and emptying: randomized controlled study evaluation by real-time ultrasonography

Background Improvement in subjective symptoms has been reported in functional dyspepsia (FD) patients administered with acotiamide. Improvement was confirmed in meal‐related symptoms, such as postprandial fullness, upper abdominal bloating, and early satiety. We examined the mechanism underlying the effects of acotiamide on gastric accommodation reflex (GAR) and gastroduodenal motility in FD patients. Methods Thirty‐four FD patients (mean age, 40.4 years) were examined ultrasonographically before and after 14–18 days of acotiamide (100 mg t.i.d.) or placebo administration. To assess GAR, expansion rate in cross‐sectional area of the proximal stomach was measured after every 100‐mL ingestion, using a straw, of up to 400 mL of a liquid meal (consommé soup, 13.1 kcal; 400 mL) in a supine position. Next, we measured gastric emptying rate (GER), motility index (MI, antral contractions), and reflux index (RI, duodenogastric reflux) to assess gastroduodenal motility. Patients also completed a survey based on the seven‐point Likert scale both before and after drug administration. Key Results Of the 37 cases, 19 and 18 were administered with acotiamide and placebo A respectively, significant difference was observed in GAR between the acotiamide and placebo groups (21.7%vs 4.4%) after 400 mL ingestion. GER significantly accelerated after treatment in the acotiamide group (P = 0.012), no significant differences were observed in MI and RI between the two groups. Improvement rates were 35.3 and 11.8% for the acotiamide and placebo groups. Conclusions & Inferences Acotiamide significantly enhances GAR and GER in FD patients. Acotiamide may have therapeutic potential for FD patients.     

Gastric motor disturbances in patients with idiopathic rapid gastric emptying

Background The mechanisms of ‘idiopathic’ rapid gastric emptying, which are associated with functional dyspepsia and functional diarrhea, are not understood. Our hypotheses were that increased gastric motility and reduced postprandial gastric accommodation contribute to rapid gastric emptying. Methods Fasting and postprandial (300 kcal nutrient meal) gastric volumes were measured by magnetic resonance imaging (MRI) in 20 healthy people and 17 with functional dyspepsia; seven had normal and 10 had rapid gastric emptying. In 17 healthy people and patients, contractility was analyzed by spectral analysis of a time‐series of gastric cross‐sectional areas. Logistic regression models analyzed whether contractile parameters, fasting volume, and postprandial volume change could discriminate between health and patients with normal or rapid gastric emptying. Key Results While upper gastrointestinal symptoms were comparable, patients with rapid emptying had a higher (P = 0.002) body mass index than normal gastric emptying. MRI visualized propagating contractions at ～3 cpm in healthy people and patients. Compared with controls (0.32 ± 0.04, Mean ± SEM), the amplitude of gastric contractions in the entire stomach was higher (OR 4.1, 95% CI 1.2–14.0) in patients with rapid (0.48 ± 0.06), but not normal gastric emptying (0.20 ± 0.06). Similar differences were observed in the distal stomach. However, the propagation velocity, fasting gastric volume, and the postprandial volume change were not significantly different between patients and controls. Conclusions & Inferences MRI provides a non‐invasive and refined assessment of gastric volumes and contractility in humans. Increased gastric contractility may contribute to rapid gastric emptying in functional dyspepsia.     

Human postprandial gastric emptying of indigestible solids can occur unrelated to antral phase III

According to animal experiments, postprandial gastric emptying of indigestible solids is mainly related to the antral phase III activity of the migrating motor complex. Gastric emptying of indigestible solids in humans has not been directly correlated to pressure recordings. The aim of the present study was to investigate the postprandial emptying pattern of indigestible solids in humans and its relation to fed and fasted antral motility. Ten healthy volunteers participated. After an overnight fast they had a standard breakfast. Two sizes of radiopaque markers (ROMs) were given with the test meal; ten cubes each of side measurement 1.5 mm and 3 mm, respectively. Emptying of the ROMs from the stomach was followed by fluoroscopy with simultaneous antral manometry. In six of the subjects, fasting antral manometry was performed on one day and on another day, the emptying of 7 mm cylindrical particles together with 3 mm cubes, in the absence of a gastric tube was recorded. All ROMs were emptied within 5 h (range 1.5-4.5 h). In all subjects, the smaller particles (1.5 mm) showed a slight, insignificant tendency to move from the stomach more rapidly than the larger (3 mm) particles. None of the subjects had an antral phase III before all ROMs were emptied from the stomach. Instead, the typical irregular postprandial pressure activity was present in all subjects until the emptying was completed. Furthermore, the highest postprandial motility index during the emptying study was far below the motility index during phase III, but comparable to the motility index during late phase II. Emptying of the 7 mm particles occurred significantly more slowly at 1.5-2.5 h, but otherwise was similar to the emptying of the smaller particles. There was no difference between emptying of the 3 mm cubes with or without the presence of the tube. Contrary to common opinion, gastric emptying of indigestible solids after a meal can occur unrelated to the antral phase III, at least up to a particle size of 3 mm and perhaps even 7 mm. These findings are of great importance for the evaluation of gastric emptying of indigestible solids, including the pharmacodynamics of orally administered drugs.     

Inhibitory effects of sildenafil on gastric motility and gastric slow waves in dogs

The aim of this study was to investigate the effects of sildenafil on gastric motility and gastric slow waves in dogs. The study was performed in healthy dogs and composed of three experiments. The first experiment was designed to study the effects of sildenafil on gastric emptying and gastric slow waves. The second experiment was used to investigate the effects of sildenafil on gastric tone. The third experiment was used to study the effects of sildenafil on postprandial antral contractions. (i) Sildenafil did not alter gastric emptying of liquid. (ii) Sildenafil had no effects on dominant frequency and percentage of normal gastric slow waves. The dominant power of gastric slow waves was, however, significantly reduced with sildenafil (P < 0.02). (iii) Fasting gastric volume with sildenafil was significantly higher than that at baseline (P < 0.0005) or in the control session (P < 0.002). However, the postprandial gastric volume was not altered with sildenafil. (iv) Sildenafil inhibited gastric antral motility. The contraction index was 338.5 +/- 39.99 at baseline and 122.5 +/- 20.3 after the injection of sildenafil (P = 0.003). Sildenafil inhibits fundic tone and antral motility but does not seem to delay gastric emptying of liquid in dogs. The amplitude but not the frequency or regularity of the gastric slow wave is inhibited by sildenafil.     

Acute effects of C-peptide on gastric emptying in longstanding type 1 diabetes

Abstract Gastric emptying (GE) of a solid (100 g beef) and liquid (150 ml 10 % dextrose) meal was measured in eight patients with type 1 diabetes during intravenous infusion of C-peptide (6pmol/kg/ min) or isotonic saline. C-peptide had no effect on either solid or liquid GE.     

Advances in the physiology of gastric emptying

There have been many recent advances in the understanding of various aspects of the physiology of gastric motility and gastric emptying. Earlier studies had discovered the remarkable ability of the stomach to regulate the timing and rate of emptying of ingested food constituents and the underlying motor activity. Recent studies have shown that two parallel neural circuits, the gastric inhibitory vagal motor circuit (GIVMC) and the gastric excitatory vagal motor circuit (GEVMC), mediate gastric inhibition and excitation and therefore the rate of gastric emptying. The GIVMC includes preganglionic cholinergic neurons in the DMV and the postganglionic inhibitory neurons in the myenteric plexus that act by releasing nitric oxide, ATP, and peptide VIP. The GEVMC includes distinct gastric excitatory preganglionic cholinergic neurons in the DMV and postganglionic excitatory cholinergic neurons in the myenteric plexus. Smooth muscle is the final target of these circuits. The role of the intramuscular interstitial cells of Cajal in neuromuscular transmission remains debatable. The two motor circuits are differentially regulated by different sets of neurons in the NTS and vagal afferents. In the digestive period, many hormones including cholecystokinin and GLP‐1 inhibit gastric emptying via the GIVMC, and in the inter‐digestive period, hormones ghrelin and motilin hasten gastric emptying by stimulating the GEVMC. The GIVMC and GEVMC are also connected to anorexigenic and orexigenic neural pathways, respectively. Identification of the control circuits of gastric emptying may provide better delineation of the pathophysiology of abnormal gastric emptying and its relationship to satiety signals and food intake.