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.     

Role of endogenous opioids in the control of gastric sensorimotor function

Abstract Endogenous opioids have been implicated not only in the process of feeding but also in the control of gastric sensitivity and gastric motor responses, and impairment of antinociceptive opioid pathways has been hypothesized to contribute to the pathogenesis of functional dyspepsia. Our aim was to study the effect of suppression of endogenous opioid action by naloxone on gastric sensorimotor function in healthy volunteers. During intravenous administration of saline or naloxone (0.4 mg intravenous bolus followed by continuous infusion 20 μg kg^?1 h^?1), sensitivity to gastric distension, gastric accommodation and fundic phasic contractility were evaluated by barostat in 15 subjects. Nutrient tolerance and meal‐related symptoms were assessed using a satiety drinking test (n = 13), and solid and liquid gastric emptying were evaluated by breath test (n = 14). Naloxone did not influence gastric compliance and sensitivity. No effect on preprandial gastric tone was found but meal‐induced accommodation was significantly inhibited by naloxone (P = 0.031). Subjects receiving naloxone demonstrated a higher motility index before (20.8 ± 2.4 vs 28.0 ± 1.9 mL s^?1, P = 0.007) and after (15.2 ± 2.0 vs 22.7 ± 1.5 mL s^?1, P = 0.0006) the meal. Naloxone significantly decreased the amount of food ingested at maximum satiety (715.4 ± 77.7 vs 617.3 ± 61.3 mL, P = 0.03). No effect of naloxone on gastric emptying was observed and intensity of postprandial symptoms was unchanged. These observations suggest that endogenous opioids are involved in the control of gastric accommodation and phasic contractility but not in the control of sensitivity to gastric distension or gastric emptying in healthy volunteers.     

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.     

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.     

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.     

Is there any association between disturbed gastrointestinal visceromotor and sensory function and impaired quality of life in functional dyspepsia?

Background Functional dyspepsia (FD) is now categorized into the epigastric pain syndrome (EPS) and the postprandial distress syndrome (PDS). However, the role of disturbed gastric emptying and sensory function for the reduction of health‐related quality of life (HRQOL) has not yet been studied in EPS and PDS. Methods A total of 300 refractory FD patients and 450 healthy blood donors (BD) were studied. BD were stratified in subjects with (BD+) and without (BD?) concomitant FD symptoms. Gastric motor and sensory function, generic and disease‐specific HRQOL [physical (PCS) and mental component summary (MCS)] and affective disorders were assessed. Twenty randomly selected BD?, 50 BD+ (36 PDS, 72%), and 110 FD (95 PDS, 86.4%) patients had additional function testing. Key Results Health‐related quality of life was significantly reduced in FD patients (PCS = 40.7 ± 8.8, MCS = 39.7 ± 11.3, both P < 0.0001) compared to BD+ (PCS = 52.0 ± 7.6, MCS = 49.0 ± 9.4) and BD? (PCS = 56.0 ± 4.3, MCS = 52.8 ± 7.2). GET (t_½, min) was significantly (both P < 0.0001) longer in FD patients (143.0 ± 7.3) compared to BD+ (101.1 ± 6.3) and BD? (73.8 ± 7.6). FD patients scored significantly higher for ‘pain’ (P < 0.0001) and ‘nausea’ (P = 0.023), there was no difference for ‘fullness’ compared to BD. Impairment of GET was not associated with HRQOL. In FD patients, an augmented symptom response to the test meal (fullness, nausea) was associated with MCS, there was no difference between FD patients with EPS or PDS. Conclusions & Inferences In EPS and PDS, delayed gastric empting and altered sensory function are disease markers but not directly linked to the severity of HRQOL impairment or clinical presentation of FD.     

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.     

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.     

Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans

Background Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short‐term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis during a 6‐h infusion in humans. Methods Ghrelin (15 pmol kg^?1 min^?1) or saline was infused intravenously for 360 min after intake of radio‐opaque markers, acetaminophen, and lactulose after a standardized breakfast in 12 male volunteers. Gastric emptying, orocecal transit, colonic transit, postprandial plasma concentrations of glucose, insulin, glucagon‐like peptide‐1 (GLP‐1), and peptide YY were assessed. In vitro studies of gastrointestinal muscle contractility were performed. Key Results The gastric emptying rate was faster for ghrelin compared to saline (P = 0.002) with a shorter half‐emptying time (50.3 ± 3.9 vs 59.9 ± 4.4 min, P = 0.004). There was no effect of ghrelin on orocecal or colonic transit. Postprandial elevations of plasma glucose, insulin, and GLP‐1 occurred 15 min earlier and were higher with ghrelin. The insulinogenic index did not change during ghrelin infusion. Basal in vitro contractility was unaffected by ghrelin. Conclusions & Inferences The effect of a 6‐h ghrelin infusion on gastrointestinal motility is limited to the stomach without affecting orocecal or colonic transit. Plasma glucose, insulin, and GLP‐1 are elevated postprandially, probably as a result of the hastened gastric emptying. Changes in glucose homeostasis as a consequence of stimulated gastric emptying and hormone release, need to be taken into account in the use of pharmacological stimulants for the treatment of motility disorders.     

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.     

Variation of symptoms during the menstrual cycle in female patients with gastroparesis

Background Gastroparesis, a chronic gastric motility disorder with symptoms of nausea, vomiting, early satiety, postprandial fullness and bloating, predominantly affects women. Some studies suggest that gastric emptying may be slower in females especially during the luteal phase of the menstrual cycle when estrogen and progesterone levels are elevated. In females with irritable bowel syndrome, symptoms may worsen during the luteal phase. The aim of this study was to determine if symptoms of gastroparesis vary along the menstrual cycle and to determine the effect of oral contraceptive agents (OCPs) on symptoms. Methods Thirty‐nine premenopausal women were studied (10 gastroparesis patients not on OCPs, 10 gastroparesis on OCPs, nine healthy women not on OCPs and 10 healthy women on OCPs). The Gastroparesis Cardinal Symptom Index Daily Diary was used to assess daily symptoms (0 = none and 5 = very severe). Key Results Gastroparesis patients not on OCPs had significantly worse symptoms during the luteal phase compared to the follicular phase for nausea (2.25 ± 0.68 vs 1.58 ± 1.06; P < 0.001) and early satiety (2.80 ± 0.50 vs 1.70 ± 1.50; P < 0.001), but not for vomiting, bloating, abdominal pain, fullness, or loss of appetite. Gastroparesis patients on OCPs showed little day‐to‐day variation of symptoms. Vomiting was more severe in patients off OCPs (2.00 ± 0.80 vs 1.20 ± 0.83; P = 0.040). Healthy women exhibited little to no symptoms regardless of OCP use. Conclusions & Inferences Increased symptoms, particularly nausea and early satiety, occurred in the luteal phase of the menstrual cycle in female patients with gastroparesis. A variation in symptoms was not seen in gastroparesis female patients on hormonal contraception.     

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.     

Effect of proximal gastric volume on hiatal hernia

Background Spatial separation of the diaphragm and the lower esophageal sphincter (LES) occurs frequently and intermittently in patients with a sliding hiatus hernia and favors gastro‐esophageal reflux. This can be studied with high‐resolution manometry. Although fundic accommodation is associated with a lower basal LES pressure, its effect on esophagogastric junction configuration and hiatal hernia is unknown. Therefore, the aim of this study was to investigate the relationship between proximal gastric volume, the presence of a hiatal hernia profile and acid reflux. Methods Twenty gastro‐esophageal reflux disease (GERD) patients were studied and compared to 20 healthy controls. High‐resolution manometry and pH recording were performed for 1 h before and 2 h following meal ingestion (500 mL per 300 kcal). Volume of the proximal stomach was assessed with three‐dimensional ultrasonography before and every 15 min after meal ingestion. Key Results During fasting, the hernia profile [2 separate high‐pressure zones (HPZs) at manometry] was present for 31.9 ± 4.9 min h^?1 (53.2%) in GERD patients, and 8.7 ± 3.3 min h^?1 (14.5%) in controls (P < 0.001). In GERD patients, the presence of hernia profile decreased during the first postprandial hour to 15.9 ± 4.2 min h^?1, 26.5%, P < 0.01 whilst this phenomenon was not observed in controls. The rate of transition between the two profiles was 5.7 ± 1.1 per hour in GERD patients and 2.5 ± 1.0 per hour in controls (P < 0.001). The pre and postprandial acid reflux rate in GERD patients during the hernia profile (6.4 ± 1.1 per hour and 18.4 ± 4.3 per hour respectively) was significantly higher than during reduced hernia (2.1 ± 0.6 per hour; P < 0.05 and 3.8 ± 0.9 per hour; P < 0.05). A similar difference was found in controls. Furthermore, an inverse correlation was found between fundic volume and the time the hernia profile was present (r = ?0.45; P < 0.05) in GERD patients, but not in controls. Conclusions & Inferences (i) In GERD patients a postprandial increase in proximal gastric volume is accompanied by a decrease in hernia prevalence, which can be explained by a reduction of the intra‐thoracic part of the stomach. (ii) A temporal hernia profile also occurs in healthy subjects. (iii) During the hernia profile, acid reflux is more prevalent, especially after meal ingestion.     

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.     

Tissue ghrelin level and gastric emptying rate in adult patients with celiac disease

Abstract Celiac disease (CD) patients show a number of gastrointestinal motor abnormalities. Ghrelin, a gastric peptide implicated in short‐term feeding control and long‐term body weight regulation, has been recently considered a key regulator of gastric motility. The aim of this study was to evaluate the gastric emptying rate of solids and the density of ghrelin‐immunopositive cells in adult CD patients before and at least 1 year after starting a gluten‐free diet. Twenty CD patients (M 8/F 12; mean age 36 years) and 10 controls underwent endoscopy with gastric and duodenal biopsies and ¹³C‐octanoic acid breath test to measure gastric emptying of solids. Celiac disease patients repeated the protocol at least 1 year after starting gluten‐free diet. Ghrelin tissue levels were evaluated by immunohistochemistry on gastric mucosa specimens. Gastric emptying time was normal in all control subjects (t_1/2 = 89 ± 16 min) while it was delayed in CD patients prior to gluten‐free diet (t_1/2 = 252 ± 101 min; P < 0.005). The mean number of ghrelin‐positive cells/field (×400) was 14.4 ± 2.7 in controls and 25.3 ± 5.7 in CD patients respectively (P < 0.0001). Gluten withdrawal was effective in normalizing gastric emptying time in all CD patients (97 ± 14 min; P < 0.0001) and resulted in a significant reduction of the density of ghrelin‐immunopositive cells (19.8 ± 5.4; P < 0.0001). The density of ghrelin‐positive cells correlated directly with the degree of duodenal damage (P < 0.001) and inversely with the body mass index of CD patients (P < 0.0001). However, in neither CD patients nor controls, a correlation between tissue ghrelin levels and gastric emptying rate was detected. In conclusion, tissue ghrelin level does not correlate with gastric emptying rate in adult CD patients and in controls.     

G-protein β3 subunit 825CC genotype is associated with postprandial distress syndrome with impaired gastric emptying and with the feeling of hunger in Japanese

Background G‐protein dysfunction related alteration of intracellular signal transduction might be linked to various abnormalities of functional gastrointestinal (GI) disorders. Serotonin (5‐hydroxytryptamine; 5‐HT) as well as G‐protein is also key signaling molecule sensorimotor functions in the GI tract. Thus, this study aims to evaluate the correlation between gastric emptying and GNβ3 and 5‐HTs polymorphisms in functional dyspepsia (FD) as defined by Rome III classification. Methods Seventy‐four patients presenting with typical symptoms of FD (epigastric pain syndrome: EPS, n = 24; postprandial distress syndrome: PDS, n = 51) and sixty‐four healthy volunteers were enrolled. Gastric motility was evaluated with the T_max value using the ¹³C‐acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and SRQ‐D scores to determine depression status. GNβ3‐C825T, 5‐HT_1A‐C1019G, 5‐HT_2A‐G1438A, 5‐HT_3A‐C42T, and 5‐HT_4A‐G353 + 6A polymorphisms were analyzed in DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. Key Results There was a significant relationship (P = 0.045) between GNβ3 825CC genotype and PDS patients without gastro‐esophageal reflux symptoms with impaired gastric emptying. In Japanese, GNβ3 825CC genotype in FD patients was significantly associated (P = 0.0485) with the feeling of hunger compared with GNβ3 825CT and TT genotypes. Conclusions & Inferences Our results suggest that the GNβ3 825CC genotype is significantly associated with PDS patients without gastro‐esophageal reflux with impairments of gastric emptying and also with the feeling of hunger in patients with FD. Further studies are needed to clarify whether the GNβ3 825CC genotype is linked to disturbances of gastric emptying via altered signal transduction responses.     

Effect of lateral positioning on gastroesophageal reflux (GER) and underlying mechanisms in GER disease (GERD) patients and healthy controls

Background Posture has been shown to influence the number of transient lower esophageal sphincter relaxation (TLESRs) and gastroesophageal reflux (GER), however, the physiology explaining the influence of right lateral position (RLP), and left lateral position (LLP) is not clear. The aim of this study was to determine the influence of RLP and LLP on TLESRs and GERD after a meal in GER disease (GERD) patients and healthy controls (HC) while monitoring gastric distension and emptying. Methods Ten GERD patients and 10 HC were studied for 90 min (30 min test meal infusion, 30 min postprandial in either RLP or LLP (randomly assigned) and 30 min in alternate position). The study was repeated on a separate day in reverse position order. TLESRs, GER, and gastric emptying rate were recorded using manometry, multichannel intraluminal impedance, and ¹³C‐octanoate breath tests. Gastric distension was visualized by five serial gastric volume scintigraphy scans during the first 30 min. Key Results Gastroesophageal reflux, (GER) disease patients had increased numbers of TLESRs in RLP compared to LLP in the first postprandial hour [5 (4–14) and 4.5 (2–6), respectively, P = 0.046] whereas the number of TLESRs was not different in RLP and LLP [4 (2–4) and 4 (3–6), respectively, P = 0.7] in HC. Numbers of GER increased similar to TLESRs in GERD patients. In GERD patients, gastric emptying reached peak ¹³CO₂ excretion faster and proximal gastric distension was more pronounced. Conclusions & Inferences In GERD patients, TLESRs, GER, distension of proximal stomach, and gastric emptying are increased in RLP compared to LLP. This effect is not seen in HC.