Efficiency and efficacy of multi-channel gastric electrical stimulation

Gastric electrical stimulation (GES) using single channel has been under investigation for its therapeutic potential for gastroparesis. The aim of this study was to study the efficacy and efficiency of multi-channel GES in accelerating gastric emptying in dogs. The study was performed in eight dogs, and gastric emptying of liquid was assessed in three randomized sessions of control, one-channel GES and four-channel GES. It was found that (i) GES of both one-channel and four-channel was able to completely entrain the slow waves in the entire stomach. However, the stimulation energy required by four-channel GES was only 1% of that required by one-channel GES. (ii) Four-channel, but not one-channel, GES significantly and substantially accelerated gastric emptying. An increase of 121.0 and 93.9% was noted with four-channel GES at 30 and 60 min after the meal, respectively. It was concluded that four-channel GES is substantially more efficient and effective than conventional single-channel GES in improving gastric emptying. It is worthy to explore its therapeutic potential for gastroparesis in clinical settings.     

Effects of vasopressin and long pulse–low frequency gastric electrical stimulation on gastric emptying, gastric and intestinal myoelectrical activity and symptoms in dogs

The aim of this study was to investigate the effect of vasopressin and long pulse-low frequency gastric electrical stimulation (GES) on gastric emptying, gastric and intestinal myoelectrical activity and symptoms in dogs. The study was performed in eight healthy female dogs implanted with four pairs of gastric serosal electrodes and two pairs of small bowel serosal electrodes, and a duodenal fistula for the assessment of gastric emptying. Each dog was studied in three sessions on three separate days in a randomized order with recordings of gastric and small bowel slow waves. Each study session consisted of 30-min baseline, 30-min stimulation and 30-min recovery period. In sessions 1 and 2, infusion of either saline or vasopressin (0.75 U kg(-1) in 30 mL saline instilled in 30 min) was given during the second 30-min period. The protocol of session 3 was the same as session 2 except long pulse-low frequency GES was performed during the second 30-min period. It was found that: (i) Vasopressin significantly delayed gastric emptying 30 and 45 min after meal and GES did not improve the vasopressin induced delayed gastric emptying; (ii) Vasopressin induced gastric dysrhythmias and GES significantly improved vasopressin induced gastric dysrhythmia; (iii) Vasopressin also induced intestinal slow wave abnormalities but GES had no effect on vasopressin induced small bowel dysrhythmia; (iv) Vasopressin induced symptoms and behaviours suggestive of nausea that were not improved by GES. We conclude that: (i) Vasopressin delays gastric emptying and induces gastric and small bowel dysrhythmias and symptoms in the fed state, and (ii) long pulse-low frequency GES normalizes vasopressin induced gastric dysrhythmia with no improvement in gastric emptying or symptoms.     

Effect of high-frequency gastric electrical stimulation on gastric myoelectric activity in gastroparetic patients

The aim of this study was to investigate the effect of gastric electrical stimulation (GES) on gastric myoelectric activity (GMA) and to identify possible mechanisms that could help explain how high-frequency GES is effective in treating nausea and vomiting associated with gastroparesis. Fifteen gastroparetic patients who received high-frequency GES were enrolled. Two pairs of temporary pacing wires were implanted on the serosa of the stomach along the greater curvature during surgery for placement of the permanent stimulation device. Two-channel serosal recordings of GMA before and during GES were measured. A gastric emptying test and severity of nausea and vomiting were assessed at baseline and at 3 months of GES. Power spectral and cross correlation analyses revealed that impaired propagation of slow waves (50%), tachygastria (30%) and abnormal myoelectric responses to a meal (50%) were the main abnormalities observed at baseline. GES with a high frequency significantly enhanced the slow wave amplitude and propagation velocity, and resulted in a significant improvement in nausea and vomiting but did not entrain the gastric slow wave or improve gastric emptying after 3 months of GES.     

Effects of gastric electrical field stimulation with long pulses on gastric emptying in dogs

The aim was to investigate the effects of electrical field stimulation (EFS) with long and short pulses on gastric emptying, gastric contractility and vagal activity in dogs. Sixteen dogs were equipped with a duodenal cannula, electrodes and strain gauges (10 dogs) in the stomach. Each dog was fed with Ensure and gastric effluent was collected from the cannula. Electrical stimulation was applied via two electrodes (about 12 cm apart, one in the corpus and the other in the antrum) with long pulses (a frequency of 6 cycles min-1, pulse amplitude of 6 mA and width of 100 ms) in 10 dogs and with short pulses (frequency of 30 Hz and pulse width of 300 micros) in six dogs. The electrocardiogram was also recorded and heart rate variability was derived to assess the vagal activity. It was found that: (i). EFS with long pulses did not alter gastric emptying during stimulation but increased gastric emptying during the 45 min immediately after stimulation; (ii). EFS with long pulses increased gastric contractility in both proximal and distal antrum during and after the stimulation; (iii). EFS with long pulses resulted in an increase in vagal tone during the 45 min immediately after stimulation. However, there is no difference during the 45 min period of stimulation; (iv). EFS with short pulses had no effect on gastric emptying. We concluded that long pulse gastric electrical field stimulation with one electrode in the corpus and the other electrode in the antrum has postponed effects on gastric emptying of liquid, gastric contractility and vagal activity.     

Intestinal electrical stimulation improves delayed gastric emptying and vomiting induced by duodenal distension in dogs.

The aim of this study was to investigate the effects of short-pulse intestinal electrical stimulation (IES) on duodenal distention-induced delayed gastric emptying and vomiting in dogs and its possible mechanisms. The study was performed in 12 dogs with jejunal electrodes and a duodenal cannula in three separate experiments to investigate the effects of IES on duodenal distension (DD)-induced delayed gastric emptying and discomfort signs, vagal efferent activity, and jejunal tone. We found that: (i) IES significantly accelerated gastric emptying of liquid delayed by distension (18.05 +/- 4.06%vs. 7.18 +/- 1.99%, P = 0.036 at 60 min). (ii) IES significantly reduced vomiting and discomfort/pain induced by distension. The average signs score was 15.33 +/- 1.37 during distension which decreased to 6.50 +/- 0.91 (P = 0.0002) with IES. (iii) IES did not change vagal afferent activity, which was assessed by the spectral analysis of the heart rate variability. (iv) IES decreased jejunal tone. In conclusion, IES with parameters commonly used in gastric electrical stimulation for nausea and vomiting associated with gastroparesis improves DD-induced delayed gastric emptying and prevents DD-induced vomiting and discomfort signs. Further studies are warranted to investigate the therapeutic potential of IES for gastrointestinal symptoms associated with disturbances in motility and sensory function in small intestine.     

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.     

Association between changes in symptoms and gastric emptying in gastroparetic patients treated with gastric electrical stimulation

Abstract  To investigate whether there is an association between gastric emptying rate and symptom improvement in gastroparetic patients treated with gastric electrical stimulation (GES), we retrospectively reviewed 63 gastroparetic patients who received GES therapy for at least 1 year. Patient characteristics, seven upper gastrointestinal (GI) symptoms and 4-h standardized gastric emptying test (GET) were evaluated at baseline and at 1 year of GES. All symptoms were significantly reduced ( P  <   0.001). Mean gastric retention was reduced by 7% ( P  =   0.102) for measurement at 4 h. Of the 63 patients, 14 had their GET normalized and 49 remained delayed after 1 year. Normalized GET patients had a similar symptom improvement as those whose GET remained delayed. Of all upper GI symptoms, the improvements in vomiting ( P  =   0.04), nausea ( P  =   0.002) and epigastric pain ( P  =   0.001) were significantly correlated with reduction in 4-h gastric retention between baseline and 12 months of GES therapy for patients with normalized gastric emptying but there were no correlations with any symptoms and change in gastric emptying for those patients who remained delayed. In summary, overall gastric emptying is not significantly accelerated at 4 h after successful symptomatic improvement with GES but nausea, vomiting and epigastric pain can be correlated with normalization of GET in a subset of patients.     

Gastric electrical activity and gastric emptying in term and preterm newborns

The aims of this study were to evaluate the gastric electrical activity and gastric emptying in preterm and term newborns and to assess the development of gastric motility by comparing newborns of different gestational ages. The cutaneous electrogastrography and the ultrasonographic study of the gastric emptying were performed before and after milk formula in three groups of infants: 12 preterm newborns with a gestational age of 28-32 weeks, 11 preterm newborns with a gestational age of 32-36 weeks, and 10 full-term newborns with a gestational age of 36-40 weeks. All recording sessions were performed 1 week after infants had reached full enteral feeding. The percentage of normal slow waves was similar in the three groups but it was not predominant compared to tachygastria in the earliest premature infants (59.3% (12.7-92.3) vs. 29.6% (3.7-78.8); P < 0.05). In addition, a progressive increase in the normal slow wave percentage (59.3% (17.4-87.4), 60.9% (38.1-89.7), 77.8% (66.4-84.8); P < 0.05) was observed as gestation advanced. As regards gastric emptying parameters, the antral area was greater and T(1/2) was longer in the preterm newborns of 28-32 weeks than preterm newborns of 32-36 weeks and full-term newborns (fasting antral area: 0.96 cm2 (0.6-1.5), 0.63 cm2 (0.4-1.2), 0.55 cm2 (0.1-0.9) respectively, P < 0.05; T(1/2): 83.4 min (76.0-108.5), 70 min (57.5-89.5) and 71.8 min (54.9-81.2), respectively P < 0.05). The comparisons of gastric emptying curves made among the three groups showed a reduced antral dilatation in preterm newborns of 28-32 weeks compared to full-term newborns at 30 and 60 min after a meal. In conclusion, although enteral feeding is important for the development process of gastrointestinal motility, gastric electrical activity and gastric emptying show an intrinsic maturation depending on the gestational age.     

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.     

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.     

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.     

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 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.     

Loxiglumide abolishes the effects of intraduodenal oleic acid on gastric motility and emptying in the pig

Abstract The role of cholecystokinin in mediating the effects of intraduodenal fat infusion on gastric motility and gastric emptying and the pattern of transpyloric flow was evaluated in conscious pigs. Concurrent measurements of antropyloroduodenal motility with an eight-channel sleeve/sidehole catheter, transpyloric flow and gastric emptying after instillation of 1000 ml of saline into the stomach, were made during intraduodenal infusion of either normal saline or oleic acid at 5 ml min⁻¹. Studies with intraduodenal oleic acid were performed with and without intravenous infusion of loxiglumide (30 mg kg⁻¹ intravenous bolus 15 min before intraduodenal oleic acid, followed by intravenous infusion of 10 mg kg⁻¹ h⁻¹), Intraduodenal oleic acid was associated with stimulation of isolated pyloric pressure waves (P < 0.05), inhibition of antral pressure waves (P < 0.05), reduced pulsatile transpyloric flow (P < 0.05) and retardation of gastric emptying (P < 0.05). when compared to intraduodenal saline. Loxiglumide prevented retardation of gastric emptying by intraduodenal oleic acid (P < 0.05), and maintained it at values that were not significantly different from saline. After loxiglumide there were more antral pressure waves (P < 0.05) and less isolated pyloric pressure waves (P < 0.05) when compared to oleic acid.
These results indicate that the effects of intraduodenal oleic acid on gastric and pyloric motility, and gastric emptying are largely mediated by CCK-dependent mechanisms.     

Effect of itopride on gastric emptying in longstanding diabetes mellitus

Abstract Delayed gastric emptying (GE) occurs in 30–50% of patients with longstanding type 1 or 2 diabetes, and represents a major cause of morbidity. Current therapeutic options are limited. We aimed at evaluating the effects of itopride on GE in patients with longstanding diabetes. Twenty‐five patients (20 type 1, 5 type 2; 10 males, 15 females; mean age 45.2 ± 2.7 years; body mass index 27.5 ± 0.9 kg m^?2; duration of diabetes 20.2 ± 2.4 years) were enrolled in a double‐blind, placebo‐controlled, randomized, crossover trial. Subjects received both itopride (200 mg) and placebo t.i.d. for 7 days, with a washout of 7–14 days. GE (scintigraphy), blood glucose (glucometer) and upper gastrointestinal (GI) symptoms (questionnaire) were measured following each treatment period. The test meal comprised 100 g ground beef (^99mTc‐sulphur colloid) and 150 mL of 10% dextrose [⁶⁷Ga‐ethylenediaminetetraacetic acid (EDTA)]. There was a slight trend for itopride to accelerate both solid (P = 0.09) and liquid (P = 0.09) GE. With itopride treatment, the emptying of both solids and liquids tended to be more accelerated, as the emptying with placebo was slower (solids: r = 0.39, P = 0.057; liquids: r = 0.44, P < 0.03). Twelve (48%) patients had delayed solid and/or liquid GE on placebo and in this group, itopride modestly accelerated liquid (P < 0.05), but not solid (P = 0.39), emptying. Itopride had no effect on mean blood glucose during the GE measurement (placebo: 9.8 ± 0.6 mmol L^?1vs itopride: 9.6 ±0.6 mmol L^?1), or GI symptoms (placebo: 1.4 ± 0.4 vs itopride: 1.8 ± 0.5). Itopride, in a dose of 200 mg t.i.d. for 7 days, tends to accelerate GE of liquids and solids in longstanding diabetes. The magnitude of this effect appears to be modest and possibly dependent on the rate of GE without itopride.     

Effect of fat preload on gastric myoelectrical activity in normal humans

The aim of this study was to investigate the effect of fat preload on gastric myoelectrical activity in normal humans. The study was performed in 10 normal subjects (five males, five females) fasted for 6h or more. Gastric myoelectrical activity was recorded using surface abdominal electrodes. In the study session the subjects ingested a 40-g liquid fat meal (2 oz of lipomul) after a 30-min baseline recording. A test meal (225 kcal beef stew) was then consumed 15 min after drinking the lipomul, and the recording was continued for 2 h after the test meal. The control session performed on a separate day followed the same procedure except that the lipomul was replaced by 2 oz of water. The order of the study and control sessions was randomized. The cutaneous recording of gastric myoelectrical activity (electrogastrogram or EGG) was digitized and subjected to computerized quantitative data analysis. The peak power and the corresponding frequency of the EGG during every 15-min time interval were computed using spectral analysis. Student's t-test was applied to determine the effect of fat preload on the surface recording of gastric myoelectrical activity. It was found that: (1) the power of the 15-min EGG at the dominant frequency immediately after fat preload was significantly lower than that of the baseline EGG (P = 0.01); (2) the postprandial power increase of the EGG at the dominant frequency was significantly lower with fat preload than with placebo preload (P = 0.002); (3) the dominant frequency of the EGG was not affected by fat preload. It was concluded that fat preload significantly decreases the power of the EGG but does not affect the frequency of the gastric slow wave.     

Assessment of symptoms during gastric emptying scintigraphy to correlate symptoms to delayed gastric emptying

Background Symptoms of gastroparesis based on patient recall correlate poorly with gastric emptying. The aim of this study is to determine if symptoms recorded during gastric emptying scintigraphy (GES) correlate with gastric emptying and with symptoms based on patient recall. Methods Patients undergoing GES completed the Patient Assessment of GI Symptoms (PAGI‐SYM) assessing symptoms over the prior 2 weeks and a questionnaire for which patients graded six symptoms during GES. A Symptom Severity Index (SSI) represented the mean of six symptoms at each time point. Key Results A total of 560 patients underwent GES for clinical evaluation of symptoms. Of 388 patients included in the study: 232 patients had normal GES (NGES), 156 delayed GES (DGES), and 11 rapid GES (RGES). Symptom severity index increased pre to postprandial for each group: NGES: 0.51 ± 0.07 to 0.92 ± 0.03, DGES: 0.60 ± 0.09 to 1.13 ± 0.05, and RGES: 0.56 ± 0.12 to 0.79 ± 0.13. Delayed gastric emptying scintigraphy patients had a higher postprandial SSI than NGES patients (1.13 ± 0.05 vs 0.92 ± 0.03, P < 0.05). Postprandial symptoms of stomach fullness (1.9 ± 0.12 vs 1.5 ± 0.09; P = 0.011), bloating (1.4 ± 0.11 vs 1.1 ± 0.09; P = 0.033), and abdominal pain (1.1 ± 0.08 vs 0.7 ± 0.12; P = 0.012) were higher in DGES than NGES. Symptom severity based on PAGI‐SYM for 2 weeks prior to GES correlated with symptoms during the test for nausea (NGES, r = 0.61; DGES, r = 0.70), stomach fullness (NGES, r = 0.47; DGES, r = 0.60), and bloating (NGES, r = 0.62, DGES, r = 0.66). Conclusions & Inferences Stomach fullness, bloating, and abdominal pain recorded during GES were higher in patients with delayed gastric emptying than in patients with normal gastric emptying. Symptoms recorded during GES correlated with those during daily life by patient recall.