Influence of tegaserod on proximal gastric tone and on the perception of gastric distention in functional dyspepsia

Background Abnormalities in gastric sensorimotor function (hypersensitivity to distention and impaired meal accommodation) have been implicated in the pathophysiology of functional dyspepsia (FD). To study the effect of the 5‐HT₄ agonist tegaserod on sensitivity to gastric distention and gastric accommodation in FD. Methods Thirty FD patients (7 males, mean age 42 ± 2 years) underwent a gastric barostat study on two separate occasions, 2 weeks apart, after 5 days of pretreatment with placebo or tegaserod 6 mg b.i.d. in a double‐blind randomized order. After introduction of the barostat bag, graded isobaric distentions (2 mmHg increments/2 min) were performed to determine gastric compliance and sensitivity to distention. Subsequently, the pressure level was set at intra‐abdominal pressure [minimal distending pressure (MDP)] + 2 mmHg for 90 min, with administration of a liquid meal (200 mL; 300 kcal) after 30 min. Key Results Tegaserod had no influence on MDP (7.9 ± 0.4 vs 7.4 ± 0.4 mmHg) or fasting gastric compliance (44 ± 10 vs 61 ± 6 mL mmHg^?1) and on fasting thresholds for first perception (3.6 ± 0.4 vs 4.2 ± 0.2 mmHg above MDP) or discomfort (9.9 ± 0.7 vs 10.5 ± 0.5 mmHg above MDP). Tegaserod did not alter intra‐balloon volumes before and after the meal [respectively 146 ± 14 vs 120 ± 11 and 297 ± 28 vs 283 ± 29 mL, not significant (NS)], or the amplitude of the meal‐induced gastric relaxation (151 ± 23 vs 162 ± 23 mL, NS). In the subgroup with normal gastric emptying (n = 22), tegaserod significantly enhanced meal‐induced accommodation (126 ± 23 vs 175 ± 29 mL, anova P < 0.001). Conclusions & Inferences Tegaserod does not alter gastric sensorimotor function in FD patients as a group. In the subgroup with normal gastric emptying, tegaserod 6 mg b.i.d enhanced gastric accommodation.     

Effect of mianserin on gastric sensorimotor function and gastric emptying: a randomized,placebo‐controlled,double‐blind,crossover study in healthy volunteers

Background Antidepressants such as mianserin can improve symptoms in some functional dyspeptic patients but their mechanism of action remains unclear. We aimed to assess the effects of mianserin on gastric sensorimotor function in man. Methods In this randomized, placebo‐controlled, double‐blind, crossover study 12 healthy subjects (six men) underwent a gastric barostat study and a gastric emptying breath test after 7 days pretreatment with placebo or mianserin (20 mg; p.o.). Graded isobaric and isovolumetric distentions were performed to determine gastric compliance and sensitivity. Subsequently, intrabag pressure was held constant and the volume increase after administration of a liquid meal (200 mL; 300 kcal) was studied. Breath was sampled before and after ingestion of a test meal and half‐emptying times for solids and liquids were determined from the breath samples. Mianserin was compared to placebo using t‐tests and mixed model analysis (mean ± SD). Key Results Mianserin did not affect pressures or volumes needed to induce first perception or discomfort. During isovolumetric distensions compliance was decreased after mianserin treatment (1.8 ± 0.4 vs 2.0 ± 0.3 mmHg 100 mL^?1; P < 0.05). Premeal volumes were comparable in both treatment arms (221 ± 99 vs 220 ± 88 mL), but meal‐induced relaxation during the first 30 min was significantly inhibited after mianserin treatment (F_6,40 = 2.58, P < 0.05). Mianserin did not affect either solid or liquid gastric emptying. Conclusions & Inferences Mianserin does not alter gastric emptying rate or sensitivity to gastric distension, but inhibits gastric accommodation to a meal in its early phase. These observations provide no explanation for the effects of mianserin in functional dyspeptic patients.     

Characterization of gastric volume responses and liquid emptying in functional dyspepsia and health by MRI or barostat and simultaneous 13C-acetate breath test

Abstract The assessment of gastric accommodation and emptying by different methodologies provides inconsistent results. We aimed to compare magnetic resonance imaging (MRI), barostat and ¹³C‐acetate breath test (BT) for the assessment of gastric volume responses and emptying in healthy controls (HC) and patients with functional dyspepsia (FD). Eight HC and eight FD patients underwent: (i) continuous BT with simultaneous MRI in the upright position after ingestion of isocaloric, 300 kcal, 200 and 800 mL meals, both labelled with 100 mg of ¹³C‐acetate; and (ii) BT with gastric barostat after ingestion of the 200 mL meal. MRI measured total gastric volume and gastric content volume (GCV) at baseline, after filling and during emptying. Meal emptying half‐times (T½) for MRI and BT were calculated (mean ± SD). We found: (i) Initial GCV was lower in FD than in HC (762 ± 22 vs 810 ± 52 mL, P < 0.04) after the 800 mL meal but not the 200 mL meal. T½_MRI was shorter for the 800 mL than the 200 mL meal (P < 0.001), but similar in HC and FD (200 mL: HC 117 ± 30 min vs FD 138 ± 42 min, ns; 800 mL: HC 71 ± 16 min vs FD 78 ± 27 min, ns). In contrast, T½_BT was similar between meals and groups (200 mL: HC 111 ± 11 min vs FD 116 ± 19 min; 800 mL: HC 114 ± 14 min vs FD: 113 ± 17 min). (ii) Barostat measurements showed similar postprandial volume increases between groups. We conclude that direct measurements by MRI provide a sensitive, non‐invasive assessment of gastric accommodation and emptying after a meal. In contrast to MRI, BT did not detect faster emptying of high‐volume compared to low‐volume liquid nutrient meals in HC or FD.     

Oxytocin reduces satiety scores without affecting the volume of nutrient intake or gastric emptying rate in healthy subjects

Background Oxytocin is expressed throughout the gastrointestinal tract and is released in response to a fatty meal. Administration of an oxytocin receptor antagonist prolongs the gastric emptying rate. The aim of this study was to examine the effect of oxytocin on gastric accommodation, gastric emptying time, and satiety after food intake. Methods Ten healthy subjects participated in a slow satiety drinking test with a liquid meal. Every 5 min the subjects scored their sensation of satiety using a visual analogue scale (VAS) until maximum satiety was reached and the amount of liquid intake was determined. Twelve subjects participated in a gastric emptying test. They were given a standardized meal containing 20 radio‐opaque markers, after which fluoroscopy was performed and VAS was scored every hour. Both tests were performed four times during infusions of saline and three different oxytocin concentrations. Blood was collected for oxytocin concentration measurements. Key Results There were no differences in the volume of nutrient intake at maximum satiety between the three doses of oxytocin and saline. However, lower satiety scores at maximum satiety were seen after oxytocin infusion (P = 0.031), with 40 mU min^?1 being the most effective dosage (P = 0.013), and this was also true 30 min after finishing the meal (P = 0.032). There was no difference in gastric emptying time between saline and oxytocin. The oxytocin concentration in plasma was increased proportional to the oxytocin infusions. Conclusions & Inferences Infusion of oxytocin reduces satiety without affecting the volume of nutrient intake or gastric emptying in healthy subjects.     

Influence of experimentally induced anxiety on rectal sensorimotor function in healthy humans

Abstract Psychological processes, especially anxiety, may have an influence on visceral perception and gastrointestinal (GI) motor function, thereby eliciting or aggravating GI symptoms. Anxiety has been shown to affect gastric sensorimotor function but it is conceivable that anxiety affects not only the stomach but also other parts of the GI tract, such as the rectum. The aim of this study was to investigate whether experimentally induced anxiety would alter rectal sensorimotor function in health. Eighteen healthy subjects (mean age 26.97 ± 1.75 years) underwent a rectal barostat study. To assess sensitivity to rectal distension and rectal compliance, stepwise isobaric distension was performed during anxious and neutral emotional state. Two methods of emotion induction were used simultaneously: audiotape assisted recall of a neutral or anxious autobiographical experience and viewing of a set of validated neutral or fearful facial expressions. Anxiety levels were assessed by means of the Spielberger State‐Trait Anxiety Inventory (STAI) and anxiety scores on a Likert scale. Anxiety scores (AUC: 2.11 ± 1.45 vs 42.78 ± 6.17 mm mmHg, P < 0.0001) and STAI scores (36.06 ± 2.09 vs 45.56 ± 2.52, P = 0.005) confirmed the efficacy of anxiety induction. Rectal compliance was not different during anxious compared with neutral emotional state (11.62 ± 0.93 vs 10.61 ± 0.96 mL mmHg^?1, P = NS). Pressure and volume thresholds inducing discomfort during rectal distension were not significantly different during anxious and neutral emotional state (29.33 ± 1.41 vs 29.78 ± 1.49 mmHg, P = NS and 249.26 ± 16.22 vs 231.38 ± 21.19 mL, P = NS respectively). Contrary to its influence on gastric sensorimotor function, experimentally induced anxiety does not affect rectal sensitivity or rectal compliance in healthy subjects.     

The effect of gastric secretion on gastric physiology and emptying in the fasted and fed state assessed by magnetic resonance imaging

Abstract Conventional measurement of gastric secretion is invasive and cannot assess the intra‐gastric distribution of gastric contents or the effects of secretion on gastric function. This study assessed the effect of gastric secretion on gastric volume responses and emptying (GE) using a validated fast T₁ mapping magnetic resonance imaging (MRI) technique. Twelve healthy participants were studied in the fasted state and after 200 kcal Gadolinium‐DOTA labelled glucose meal during intravenous infusion of pentagastrin or placebo in double‐blind, randomized order. Total gastric volume (TGV) and gastric content volume (GCV) was assessed by MRI volume scans and secretion by fast T₁ mapping. Data was described by the κ‐coefficient (volume change after meal ingestion), by GE half time (T₅₀) and maximal GE rate (GER_max) derived all from a GE model. Pentagastrin increased GCV and TGV compared to placebo [κ(GCV):1.6 ± 0.1 vs 0.6 ± 0.1; κ(TGV): 1.6 ± 0.1 vs 0.7 ± 0.1; P < 0.001]. T₁ maps revealed a secretion layer above the meal, the volume of which was associated with κ (R² = 83%, P < 0.001). TGV and GCV change were similar in both conditions (κ; P = ns). T₅₀ was higher for pentagastrin than for placebo (84 ± 7 vs 56 ± 4min, P < 0.001); however, GER_max was similar (5.9 ± 0.6 vs 4.9 ± 0.4 mL min^?1, P = ns). This study shows volume and distribution of gastric secretion can be quantified in‐vivo by non‐invasive MRI T₁ mapping. Increased GCV drove TGV accommodation without evidence of a direct effect of pentagastrin or excess acid on gastric function. Secretion increases GCV thus prolongs GE as assessed by T₅₀; however, GE rate is unchanged.     

Gastric tone,volume and emptying after implantation of an intragastric balloon for weight control

Background The intragastric balloon, filled with air or liquid is used before elective bariatric surgery because its efficacy is limited. This might be the consequence of altered gastric functions. Therefore, we aimed to investigate, in an animal model, the changes in gastric motility and emptying induced by long‐term insertion of a balloon used for weight reduction. Methods Ten Göttingen mini‐pigs were allocated into two groups with and without an intragastric balloon for 5 months. Balloons were inserted under endoscopy during general anesthesia and were filled with 350 mL of air. Gastric emptying was evaluated by scintigraphy. Gastric volume was measured by single photon emission computed tomography and proximal gastric compliance obtained using an electronic barostat. Changes in vagal tone were assessed by heart rate variability (HRV). Key Results After balloon insertion, gastric volume was significantly increased (2047 ± 114.8 cm³ after vs 1674 ± 142.5 cm³ before insertion, P < 0.05). Gastric compliance was also larger in balloon group (219 ± 23.4 mL mmHg^?1 in balloon vs 168 ± 7.7 mL mmHg^?1 in control group). Gastric emptying was reduced after insertion of the balloon (T_1/2 = 204 ± 28.8 min vs 159 ± 25.4 before vs after insertion). High frequency components of the spectral analysis of HRV, representing vagal tone, were increased in balloon group. Conclusions & Inferences The proximal stomach was enlarged after the insertion of a balloon in the stomach as a consequence of an increased gastric compliance. This change in compliance was probably causative for a reduction in gastric emptying rate of solids. These alterations were associated with increased vagal tone.     

Assessment of gastric motor function in childhood functional dyspepsia and obesity

Background The aim was to compare gastric emptying rate and nutrient tolerance during a satiety drinking test in children with functional dyspepsia (FD) and obesity and to study the relationship between daily caloric intake and the satiety drinking test. Methods A total of 28 dyspeptic children (22 girls, mean age 12.5 ± 3.1 years) and 15 obese children (five girls, 13.3 ± 1.8 years) were studied. The patients underwent an octanoic acid gastric emptying breath test and a satiety drinking test. Prior to both tests, a dyspepsia questionnaire was filled out to calculate the mean calorie intake. Key Results The most prevalent dyspeptic symptoms were early satiety (96.4%), postprandial fullness (89.2%), and epigastric pain (78.6%), followed by nausea (50%). All dyspeptic and obese children (n = 43) started the satiety drinking test and 41 children completed the test until a score of 5 was reached. The maximum ingested volume in FD was significantly lower than in obesity or in age‐matched healthy controls (252 ± 85 vs 479 ± 199 and 359 ± 29 mL respectively, both P < 0.05). As a group, dyspeptic children had significantly slower gastric emptying than obese children (89.7 ± 54.8 min vs 72.5 ± 26.0 min, P = 0.05). Daily calorie intake was significantly higher in obese children than that in dyspeptic children (2325 ± 469 vs 1503 ± 272 cal, P < 0.0001). The endpoint of the satiety drinking test was significantly correlated with body weight or BMI (both R = 0.41, P = 0.04), but not with daily calorie intake, gastric emptying rate or age. Conclusions & Inferences The satiety drinking test is a potentially useful non‐invasive tool in the investigation of children with FD and obesity.     

Increased severity of dyspeptic symptoms related to mental stress is associated with sympathetic hyperactivity and enhanced endocrine response in patients with postprandial distress syndrome

Background Mental stress (MS) may alter gastric sensory‐motor function. The aim of the study was to assess postprandial autonomic nervous system activity and stress hormones in response to acute mental stress in dyspeptic patients. Methods A total of 25 patients with postprandial distress syndrome (PDS; 11 mol L^?1, age 35.9 ± 9.3 years) and 12 healthy controls (5 mol L^?1, age 25.8 ± 4.6 years) underwent electrogastrography and ¹³C‐octanoate gastric emptying study using a 480 kcal solid meal. Heart rate variability (LF/HF ratio) and corticotrophin‐releasing factor, adrenocorticotropic hormone (ACTH), and cortisol serum levels were also evaluated. Dyspeptic symptoms were scored by analogue visual scale and expressed as symptoms total score (TS). The protocol was repeated twice in each subject, with and without a mental stress test before the meal. Key Results Mental stress significantly increased postprandial symptoms severity in patients (TS: stress 111 ± 18 vs basal 50 ± 10; P < 0.05). Low‐/high‐frequency component ratio was significantly higher in patients after MS at 120 min (stress 5.46 ± 0.41 vs basal 3.41 ± 0.64; P < 0.01) and 180 min (stress 5.29 ± 0.2 vs basal 3.58 ± 0.19; P < 0.05). During stress session, in patients we found a significantly higher ACTH level than baseline at 30, 60, 90, 150, 210, 240, and 270 min and a significantly higher cortisol level at 30, 60, 90, 120, 210, and 270 min. Gastric emptying rate and electrical activity were not influenced by MS. Conclusions & Inferences In PDS patients, administration of MS before meal increases symptoms severity by inducing sympathetic hyperactivity and increased stress hormones levels. As the gastric emptying looks not altered, we conclude that these neurohormonal responses mainly affect sensitive function.     

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.     

Relationship between symptom pattern, assessed by the PAGI-SYM© questionnaire, and gastric sensorimotor dysfunction in functional dyspepsia

Abstract The patient assessment of upper gastrointestinal symptom severity index (PAGI‐SYM) questionnaire was recently developed and validated for the evaluation of therapeutic responsiveness in functional dyspepsia (FD). Functional dyspepsia is a heterogeneous disorder, with different pathophysiological mechanisms underlying the symptom pattern. The relationship between PAGI‐SYM scores and putative pathophysiological mechanisms has not been studied. The aim of this study was to evaluate the relationship between PAGI‐SYM subscales and gastric emptying, gastric sensitivity and gastric accommodation in FD. A total of 161 consecutive FD patients underwent Helicobacter pylori (HP), gastric barostat and standardized gastric emptying testing (n = 126), and completed the PAGI‐SYM questionnaire. Relationships between scores for the six subscales (heartburn/regurgitation, nausea/vomiting, fullness/satiety, bloating, upper abdominal pain, lower abdominal pain) and gastric function were analysed using Pearson’s linear correlation, multiple regression analysis, chi‐square and Student’s t‐tests. Gastric emptying was significantly correlated with scores for heartburn/regurgitation (r = 0.26), nausea/vomiting (r = 0.19), fullness/satiety (r = 0.20), bloating (r = 0.21) and lower abdominal pain (r = 0.22; all P < 0.05). Patients with delayed emptying had significantly higher scores for each of these subscales (all P < 0.05). Discomfort volume during gastric distension was significantly correlated with scores for fullness/satiety (r = ?0.27), bloating (r = ?0.23), heartburn/regurgitation (r = ?0.21), and upper abdominal pain (r = ?0.20). Patients with hypersensitivity to distension had significantly higher scores for fullness/satiety (P < 0.05). At different cut‐off levels of symptom severities, consistent associations were found between fullness/satiety and gastric discomfort volume, between preprandial volumes and upper abdominal pain, compliance and upper abdominal pain, and between bloating and gastric discomfort volume. Multiple regression analysis revealed that gastric emptying rate contributed significantly to models for the severity of these subscales. The importance of discomfort volume disappeared in favour of gender when sex was included in the model. No significant correlations were found with HP status or with gastric accommodation. PAGI‐SYM scores are mainly correlated with gastric emptying rate and with gastric hypersensitivity. Multivariate analysis suggests that the questionnaire may be useful in the evaluation of gastroprokinetics. Its role in the evaluation of drugs that alter gastric sensitivity is less clear.     

Impaired intestinal gas propulsion in manometrically proven dysmotility and in irritable bowel syndrome

Background Intestinal manometry is the current gold standard for diagnosing small bowel dysmotility; however, the functional significance of abnormal manometry is unknown. Our aim was to determine whether, and to what extent, intestinal gas propulsion is impaired in patients with manometrically proven dysmotility compared with healthy controls and patients with IBS. Methods Clearance and tolerance of a jejunal gas load (12 mL min^?1 for 2 h) were measured in 15 patients with severe abdominal symptoms and intestinal dysmotility evidenced by manometry, 15 patients with IBS and 15 healthy subjects. Thereafter, the effect of neostigmine (0.5 mg i.v. bolus) vs placebo (i.v. saline) was tested in six dysmotility patients. Key Results After 2‐h gas infusion, patients with dysmotility developed significantly more gas retention (717 ± 91 mL) than IBS patients (372 ± 82 mL; P = 0.0037) and healthy subjects (17 ± 67 mL; P < 0.0001 vs dysmotility; P = 0.0060 vs IBS). Despite the greater retention in dysmotility patients, abdominal perception (2.5 ± 0.6 score) and distension (7 ± 2 mm girth increment) were similar to IBS (3.9 ± 0.6 score and 7 ± 2 mm, respectively). In dysmotility patients, neostigmine produced immediate clearance of gas, and by 30 min had reduced gas retention (by ?552 ± 182 vs 72 ± 58 mL after saline; P = 0.008), abdominal symptoms (by ?0.8 ± 0.3 score vs 0.3 ± 0.2 after saline; P = 0.019) and distension (girth change ?5 ± 1 mm; P = 0.003 vs?2 ± 2 mm after saline). Conclusion & Inferences Patients with manometric dysmotility have markedly impaired intestinal gas propulsion. In IBS patients, impaired gas propulsion is less pronounced but associated with concomitant sensory dysfunction and poor tolerance of gas retention.     

Influence of the 5‐HT3 receptor antagonist ondansetron on gastric sensorimotor function and nutrient tolerance in healthy volunteers

Background Serotonin is believed to be involved in the regulation of the gastric accommodation reflex in man however which receptor subtype(s) are involved remains to be elucidated. Methods Eleven healthy subjects (nine men, age 19–30) underwent a gastric barostat and a drinking test after treatment with either placebo or ondansetron (8 mg intravenously). During the barostat protocol an intragastric flaccid bag was stepwise distended (2 mmHg increments 2 min) to determine gastric compliance and sensitivity to distention. Subsequently, the pressure level was set at intra‐abdominal pressure +2 mmHg while volume was followed before and after administration of a liquid meal (200 mL; 300 kcal). During the drink test volunteers drank at a rate of 15 mL min^?1 until maximal satiation. Results (mean ± SEM) were compared using t‐tests and mixed model analysis. Key Results Gastric compliance was not significantly altered by ondansetron (51.5 ± 5.6 vs 49.2 ± 5.2 mL mmHg^?1), neither were the pressure thresholds for first perception or discomfort. Ondansetron treatment did not affect basal gastric tone (173 ± 14 vs 156 ± 12 mL), neither did it affect the amplitude of the meal‐induced relaxation (160 ± 52 vs 131 ± 43 mL) or the maximum volume increase after the meal (264 ± 54 mL vs 234 ± 51 mL). During the drinking test the amount of liquid meal ingested at maximum satiation was significantly increased by ondansetron (784 ± 74 vs 907 ± 64 mL, P < 0.05). Conclusions & Inferences These data suggest that 5‐HT acting at 5‐HT₃ receptors is not involved in the control of gastric sensorimotor function, but contributes to the regulation of hunger and satiation in man.     

The nitric oxide synthase inhibitor, Ng-nitro-l-arginine-methyl-ester, attenuates the delay in gastric emptying induced by hyperglycaemia in healthy humans

Abstract The aim of this study was to determine whether the nitric oxide (NO) synthase inhibitor, N^g‐nitro‐l ‐arginine‐methyl‐ester (l ‐NAME), reverses the effects of acute hyperglycaemia on gastric emptying and antropyloroduodenal (APD) motility. The study had a four‐way randomized crossover (hyperglycaemia vs euglycaemia; l ‐NAME vs placebo) design in a clinical laboratory setting. Seven healthy volunteers [four males; age 30.3 ± 3.8 years; body mass index (BMI) 23.6 ± 1.2 kg m^?2] were the study subjects. After positioning a transnasal manometry catheter across the pylorus, the blood glucose concentration was maintained at either 15 or 5 mmol L^?1 using a glucose/insulin clamp. An intravenous infusion of l ‐NAME (180 μg kg^?1 h^?1) or placebo (0.9% saline) was commenced (T = ?30 min) and continued for 150 min. At T = ?2 min, subjects ingested a drink containing 50 g of glucose made up to 300 mL with water. Gastric emptying was measured using 3D ultrasound, and APD motility using manometry. Hyperglycaemia slowed gastric emptying (P < 0.05), and this effect was abolished by l ‐NAME. l ‐NAME had no effect on gastric emptying during euglycaemia. Hyperglycaemia suppressed fasting antral motility [motility index: 3.9 ± 0.8 (hyperglycaemia) vs 6.5 ± 0.6 (euglycaemia); P < 0.01]; l ‐NAME suppressed postprandial antral motility [motility index: 3.6 ± 0.2 (l ‐NAME) vs 5.1 ± 0.2 (placebo); P < 0.001]. Postprandial basal pyloric pressure was higher during hyperglycaemia (P < 0.001), and lower after administration of l ‐NAME (P < 0.001). Slowing of gastric emptying induced by hyperglycaemia is mediated by NO, and may involve the modulation of tonic pyloric activity.     

Abdominal accommodation induced by meal ingestion: differential responses to gastric and colonic volume loads

Background Using an experimental model of colonic gas infusion, we previously showed that the abdominal walls adapt to its content by an active phenomenon of abdominal accommodation. We now hypothesized that abdominal accommodation is a physiological phenomenon, and aimed to confirm that it can be induced by ingestion of a meal; a secondary aim was to determine whether the response to gut filling is region‐specific. Methods In healthy subjects (n = 24) a nutrient test meal was administered until tolerated at a rate of 50 mL min^?1. Electromyographic (EMG) activity of the anterior wall (upper and lower rectus, external and internal oblique) was measured via four pairs of surface electrodes, and EMG activity of the diaphragm via intraluminal electrodes on an esophageal tube. To address the secondary aim, the response to gastric filling was compared with that induced by colonic filling (1440 mL 30 min^?1 anal gas infusion; n = 8). Key Results Participants tolerated 927 ± 66 mL of meal (450–1500 mL). Meal ingestion induced progressive diaphragmatic relaxation (EMG reduction by 16 ± 2%; P < 0.01) and selective contraction of the upper abdominal wall (24 ± 2% increase in activity of the upper rectus and external oblique; P < 0.01 for both), with no significant changes in the lower rectus (4 ± 2%) or internal oblique (5 ± 3%). Colonic gas infusion induced a similar response, but with an overall contraction of the anterior wall. Conclusions & Inferences Meal ingestion induces a metered and region‐specific response of the abdominal walls to accommodate the volume load. Abnormal abdominal accommodation could be involved in postprandial bloating.     

Ameliorating effects of mirtazapine on visceral hypersensitivity in rats with neonatal colon sensitivity

Background The aim was to investigate the effects of mirtazapine on visceral hypersensitivity and gastric emptying in an established rodent model of colonic sensitization. Methods Twenty colonic sensitized rats and 20 matched controls were used. Visceral sensitivity during colorectal distension (CRD) was assessed by the measurement of abdominal electromyogram (EMG) with the pressures of 20, 40, and 60 mmHg. Mirtazapine with doses of 1, 5, and 10 mg kg⁻¹ were administered orally. Gastric emptying and small intestinal transit were performed in a separated experiment after gavage of 1.5 mL of phenol red solution. Key Results (i) Visceral hypersensitivity after neonatal colonic sensitization was confirmed. (ii) Mirtazapine dose‐dependently reduced visceral hypersensitivity in the colonic sensitized rats. The increases in EMG during CRD at 40, 60 mmHg were, 17.59 ± 6.49 and 26.04 ± 8.30, respectively, with saline session, and substantially reduced to 10.0 ± 5.95 (P = 0.02 vs corresponding saline) and 12.58 ± 7.43 (P < 0.001 vs saline) with mirtazapine at 10 mg kg⁻¹. Similar findings were noted at doses of 5 and 1 mg kg⁻¹ at a lesser degree. In the control rats, mirtazapine‐reduced visceral sensitivity only during CRD at 60 mmHg. (iii) Mirtazapine 10 mg kg⁻¹ significantly accelerated gastric emptying (P = 0.045) but slightly and marginally delayed intestinal transit (P = 0.058) the colonic sensitized rats. Conclusions & Inferences Mirtazapine dose‐dependently ameliorates visceral hypersensitivity in colonic sensitized rats. Mirtazapine at a high dose improves delayed gastric emptying in colonic sensitized rats but slightly and marginally delays small intestinal transit. Its roles in altering gastrointestinal motility need further investigation.     

Influence of sumatriptan on gastric accommodation and on antral contraction in healthy subjects assessed by ultrasonography

Background Oral sumatriptan administration has been reported to delay gastric emptying after liquid meals. The aim of this study was to determine whether delayed gastric emptying is caused by enhanced gastric accommodation, impaired antral contractions, or both using ultrasonography. Methods Ten healthy volunteers were enrolled in this randomized two‐way crossover study. After overnight fasting, the subjects received the liquid meal 60 min after ingesting a 50 mg sumatriptan tablet with 50 mL of water or 50 mL of water alone (control). The cross‐sectional area of the proximal stomach was measured in a supine position after every 100 mL. The frequency and amplitude of the antral contractions were measured in a slightly backward sitting position. The intragastric distribution of the liquid meal was assessed by calculating the proximal stomach/distal stomach ratio (prox/distal ratio). Key Results The cross‐sectional area after drinking 100, 200, and 300 mL of the liquid meal (oral sumatriptan vs control) was 34.49 vs 15.11 cm² (P = 0.0051), 48.00 vs 30.61 cm² (P = 0.0166), and 58.67 vs 47.19 cm² (P = 0.0125), respectively. There was no significant difference in the amplitude of contractions, contraction cycle, motility index, and prox/distal ratio (97.15 vs 97.93%, P = 0.0745; 19.42 vs 19.5 s, P = 0.8590; and 887.58 vs 889.22, P = 0.5751; 9.75 vs 8.41, P = 0.8785; respectively). Conclusions & Inferences Oral sumatriptan administration enhanced gastric accommodation after the ingestion of liquid nutrients, but had no significant effect on antral contractions or intragastric distribution in healthy subjects.     

Duodenal ulcer disease,gastroduodenal motor function and reflux esophagitis – a cross‐sectional survey in a subset of Taiwanese patients

Background To investigate the association between the gastric emptying rate and the presence of erosive esophagitis in duodenal ulcer (DU) patients among a population with high prevalence of Helicobacter pylori infection. Methods Cross‐sectional survey was performed in a cohort of 60 male patients with either active or healed DU, with or without the presence of erosive esophagitis. Clinical and social‐demographic data, blood level of fasting gastrin, pepsinogen I & I/II ratio, and scintigraphic measurement of half emptying time (t_1/2) of the solid phase gastric emptying were evaluated. Key Results Patients with active DU and erosive esophagitis tended to have higher plasma level of fasting gastrin than those without erosive esophagitis (75.11 ± 13.74 vs 45.81 ± 5.06 pg mL^?1, P = 0.059). In the absence of H. pylori infection, patients with healed DU and erosive esophagitis had a trend to have longer half‐emptying time (t_1/2: 96.5 ± 6.4 vs 69.1 ± 11.3 min, P = 0.0572) than those without erosive esophagitis, and statistically significant longer after excluding those diagnosed with hiatal hernia (t_1/2: 100.8 ± 7.9 min vs 69.1 ± 11.3 min, P < 0.05) from the former group. Among the healed DU patients, those with negative H. pylori infection, hiatal hernia and overweight (body mass index ≥24) had significantly increased risk of severe esophagitis. Conclusions & Inferences Presence of erosive esophagitis in a subset of Taiwanese patients with healed DU and negative H. pylori status was associated with slower solid phase gastric emptying.     

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.     

The effects of fasting duration on gastric emptying in man,an exploration of the role of the endocannabinoid system and inter‐individual responsiveness

Background In animal studies, gut vagal afferent neurons express cannabinoid (CB1) receptors, whose expression is increased by fasting. We aimed to explore the possibility that similar effects might be relevant in man in controlling gastric emptying. Methods Fourteen healthy volunteers underwent measurements of gastric emptying using the ¹³C acetate breath test, after either a nutrient (skimmed milk) or non‐nutrient (water) meal following both a 12 and 24 h fast. Further gastric emptying studies were performed with and without the CB1 receptor antagonist Rimonabant (20 mg or 80 mg). Because of the inter‐individual variations observed, two subjects underwent additional studies with and without Rimonabant to determine intra‐individual consistency. Gastric emptying was evaluated as cumulative C13 : C12 ratio values, measured at 5 min intervals for 30 min. Key Results In the group as a whole, fasting duration slowed gastric emptying for both the nutrient [120 ± 30 (mean ± SD) vs 101 ± 34, P < 0.05] and non‐nutrient [226 ± 62 vs 177 ± 47, P < 0.05] meals, but there was no effect of Rimonabant. However, there was consistent inter individual variation; thus while 12 subjects showed a slowing, two (14%) exhibited accelerated gastric emptying for both the nutrient and the non‐nutrient meal after 24 h fasting and in one of whom, Rimonabant consistently reversed the fasting effect on the non‐nutrient meal. Conclusions & Inferences Extended fasting alters the gastric emptying of liquid meals but there are consistent differences between individuals. Where there is an accelerated response to fasting, Rimonabant appears to reverse the effect.