A model for evaluation of gastric sensitivity in awake rats

We developed a model for the evaluation of gastric sensitivity to distension in awake rats. A balloon made from a latex condom was chronically placed in the stomach and three stainless steel electrodes were implanted in the neck muscles. Isobaric distensions were performed with a barostat by step of 5 mmHg with 10 min inflation and 2 min deflation. Gastric pressure, integrated neck electromyogram (EMG) and gastric volume were continuously monitored on a potentiometric recorder. Gastric distension at 15 or 20 mmHg induced a typical posture associated with contractions of the neck muscles. Pain threshold was defined as the pressure inducing an increase of integrated neck EMG greater than 100%.
The mean pain threshold was 18.5 ± 0.7 mmHg and was not modified 2, 4 and 7 days after the first experiment. However, gastric volumes were significantly higher on the 4th and the 7th days. Morphine at the doses of 0.4 and 4 mg kg⁻¹ i.p. significantly increases the pain threshold. At the doses of 0.04 and 0.4 mg kg⁻¹, morphine significantly increased gastric volume for the distending pressure of 10 mmHg. Naloxone (2.5 mg kg⁻¹ i.p.) reversed the effects of morphine. In conclusion, our model permits simultaneous evaluation of pain threshold and gastric compliance associated with gastric distension in conscious rats.     

Vagal activation by sham feeding improves gastric motility in functional dyspepsia

Abstract  Antral hypomotility and impaired gastric accommodation in patients with functional dyspepsia have been ascribed to vagal dysfunction. We investigated whether vagal stimulation by sham feeding would improve meal-induced gastric motor function in these patients. Fourteen healthy volunteers and 14 functional dyspepsia patients underwent a drink test twice, once with and once without simultaneous sham feeding. After ingesting 500 mL clear meat soup (20 kcal, 37 °C) in 4 min, sham feeding was performed for 10 min by chewing a sugar-containing chewing gum while spitting out saliva. Using two- and three-dimensional ultrasound, antral motility index (contraction amplitude × frequency) and intragastric volumes were estimated. Without sham feeding, functional dyspepsia patients had lower motility index than healthy volunteers (area under curve 8.0 ± 1.2 vs 4.4 ± 1.0 min⁻¹, P  =   0.04). In functional dyspepsia patients, but not in healthy volunteers, motility index increased and intragastric volume tended to increase by sham feeding ( P  = 0.04 and P  = 0.06 respectively). The change in motility index was negatively correlated to the change in pain score ( r  = −0.59, P  = 0.007). In functional dyspepsia patients, vagal stimulation by sham feeding improves antral motility in response to a soup meal. The result supports the view that impaired vagal stimulation is implicated in the pathogenesis of gastric motility disturbances in functional dyspepsia.     

Influence of ghrelin on the gastric accommodation reflex and on meal-induced satiety in man

Abstract  Ghrelin increases gastric tone in the fasting state and enhances gastric emptying in gastroparesis. The aims of the study were to evaluate the effect of ghrelin on postprandial gastric tone and on meal-induced satiety in health. Ten healthy volunteers underwent a barostat study on two occasions. After determination of intra-abdominal pressure (minimal distending pressure, MDP), isobaric volume measurement was performed for 90 min at MDP + 2 mmHg. After 20 min, ghrelin (40 μg) or saline was administered i.v. over 30 min in a double-blind-randomized cross-over design, followed 10 min later by a liquid meal (200 mL, 300 kcal). Stepwise isobaric distentions (+2 mmHg per 2 min) were performed 60 min after the meal. Data (mean ± SEM) were compared using paired Student's t -test and anova . Separately, a satiety drinking test (15 mL min⁻¹ until satiety score 5) was performed on 10 subjects twice, after treatment with placebo or ghrelin. Ghrelin infusion significantly inhibited gastric accommodation (mean volume increase adjusted means 108.0 ± 50 vs 23.0 ± 49 mL, P  = 0.03, ancova with the premeal postinfusion volume as covariate) and reduced postprandial gastric volumes (197.2 ± 24.6 vs 353.5 ± 50.0 mL, P  = 0.01). Pressures inducing perception or discomfort during postprandial gastric distentions were not altered. During satiety testing, ghrelin did not alter nutrient volume ingested till maximal satiety (637.5 ± 70.9 vs 637.5 ± 56.2 mL, ns). Ghrelin administered during the meal significantly inhibits gastric accommodation in health, but this is not associated with early satiation.     

Gastric hypersensitivity induced by oesophageal acid infusion in healthy volunteers

Abstract  Distal oesophageal acid exposure has been shown to increase visceral sensitivity of the proximal oesophagus via central sensitization. Here we evaluated whether acidification of the distal oesophagus also affects the sensorimotor function of the proximal stomach. A gastric barostat study combined with a 30-min acid (HCl 0.15 mol L⁻¹) or saline infusion in the distal oesophagus was performed in 18 healthy volunteers. Gastric and cutaneous sensitivity was assessed before and up to 2 h after the start of infusion. Directly after acid infusion, but not after saline, the threshold for discomfort decreased (–6.4 ± 1.7 vs 0.4 ± 0.4 mmHg; P = 0.028) and distension-induced symptoms increased significantly compared with the baseline (122 ± 49% vs −3 ± 9%). Cutaneous sensitivity remained unaffected by acid infusion. In contrast, when the infused liquid was aspirated 3 cm more distally, at the level of the lower oesophageal sphincter, the effect of acid infusion on gastric sensitivity was abolished and the increase in distension-induced symptoms was reduced (61 ± 24%). Distal oesophageal acid infusion induces visceral hypersensitivity without affecting somatic sensitivity arguing against a similar mechanism of central sensitization as observed in non-cardiac chest pain. As reduction of the acid load to the stomach prevented this effect, our findings indicate that either gastric and/or duodenal acidification is involved. It should be emphasized though that aspiration from distal oesophagus may have attenuated the effect by reducing the acid-exposed area or by reducing the contact time.     

Oxytocin receptor expressed on the smooth muscle mediates the excitatory effect of oxytocin on gastric motility in rats

Abstract  The aim of this study was to localize oxytocin receptor (OTR) in the stomach and to investigate the effect of OT on gastric motility in rats. Western blot and immunohistochemistry methods were used to localize OTR in stomach. The motility of stomach was recorded in vivo (recording of the intragastric pressure), in vitro (recording of the contraction of muscle strips) and on isolated smooth muscle cells. OTR was expressed on cells of both circular and longitudinal muscle of stomach. Systemic administration of OT induced an early transient decrease and a subsequent increase on intragastric pressure. Devazepide (1 mg kg⁻¹, i.v.), a cholecystokinin-1 (CCK₁) receptor antagonist, completely abolished the transient response but did not influence the subsequent one. OT (10⁻⁹–10⁻⁶ mol L⁻¹) dose-dependently increased the contraction of the muscle strips of gastric body, antrum, and pyloric sphincter, and decreased the average cell length of isolated smooth muscle cells. Tetrodotoxin and atropine did not influence the effect of OT on muscle strips. Pretreatment with atosiban, an OTR antagonist, inhibited the spontaneous contraction of muscle strips and abolished the excitatory effect of OT on the muscle strips and the isolated cells. These results suggest that the OTR is expressed on the smooth muscle of the stomach and mediates excitatory effect of OT on gastric motility.     

Measuring the interaction of meal and gastric secretion: a combined quantitative magnetic resonance imaging and pharmacokinetic modeling approach

Background The stimulation and intragastric accumulation of gastric secretion has been recognized as an important factor in gastroesophageal reflux disease. However, the interaction of gastric secretion and meal emptying has not been fully understood. Current methods to assess gastric secretion are either invasive or unable to provide information on its volume, distribution and dynamics. The aim of this study was to quantify the interaction between meal emptying and meal induced gastric secretion by using quantitative magnetic resonance imaging (MRI) and pharmacokinetic analysis. Methods A chocolate test meal was developed which is secretion stimulating and MRI compatible. Meal emptying and gastric secretion were assessed in fourteen healthy volunteers using a validated quantitative MRI technique. A population based pharmacokinetic model was developed and applied to the extracted volume data, assessing the meal emptying rate, rate of secretion and their interaction. Key Results The test meal continuously induced gastric secretion in all subjects, which partly accumulated at the meal–air interface, forming a ‘secretion layer’ in the proximal stomach. Traditional fitting detected a significant correlation between meal emptying rate and rate of secretion. The pharmacokinetic model quantified this interaction and estimated a 2.3 ± 1 fold higher effect of meal on secretion than vice versa. The efficacy of the emptied meal to produce gastric secretion was 61%. Conclusions & Inferences The combined quantitative MRI and pharmacokinetic model approach allows for the quantification of gastric secretion volume and its interaction on meal emptying. The observed secretion layer might explain previous findings postulating the presence of an intragastric ‘acid pocket’.     

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.     

Clinical effects of STW 5 (Iberogast®) are not based on acceleration of gastric emptying in patients with functional dyspepsia and gastroparesis

Abstract  STW 5, a herbal extract, is effective for the treatment of symptoms in patients with functional dyspepsia (FD). However, its mode of action is still unclear and a modulation of gastric motility is hypothesized. This multicentre, placebo-controlled double-blind study addressed the question of whether STW 5 accelerates gastric emptying in patients with FD and gastroparesis. One-hundred and three patients diagnosed with FD were randomly assigned to a treatment with either STW 5 or a liquid placebo for 28 days. The primary end point of the study was a change of a validated gastrointestinal symptom (GIS) score under treatment. Additionally, patients underwent a ¹³C octanoic acid breath test for the assessment of the gastric half-emptying time ( t _1/2). Patients with prolonged t _1/2 were diagnosed with gastroparesis and requested to repeat the test at the end of treatment. A change of t _1/2 was defined a secondary study end point. t _1/2 was prolonged in 48.6% of patients in the STW 5 group and in 43.8% of the placebo group. During treatment, t _1/2 increased non-significantly in patients treated with STW 5 (+23 ± 109 min; P  = 0.51) and slightly accelerated among patients in the placebo arm (−26 ± 51 min; P  = 0.77) ( P  = 0.49). The improvement of the GIS ( P  = 0.08) and the proportion of patients with a treatment response ( P  = 0.03) were more pronounced in the STW 5 group. Our findings suggest that the clinical effects of STW 5 in patients with FD and gastroparesis are not directly mediated by an acceleration of gastric emptying. A clear-cut correlation with symptom improvement is still lacking.     

Application of magnetic resonance imaging to measure fasting and postprandial volumes in humans

Abstract  Our aims were to measure the gastric volume response in excess of ingested meal volume (i.e. gastric accommodation), contribution of swallowed air to this excess, day-to-day variability of gastric volumes measured by MRI and their relationship to volumes measured by single-photon-emission computed tomography (SPECT). In 20 healthy volunteers, fasting and postprandial gastric volumes were measured after technetium^99m-pertechnetate labeling of the gastric mucosa by SPECT and separately by MRI, using 3D gradient echo and 2D half-Fourier acquisition single-shot turbo spin echo (HASTE) sequences. Ten of these subjects had a second MRI exam to assess intra-individual variation. Thereafter, another 10 subjects had two MRI studies during which they ingested the nutrient in 30 or 150 mL aliquots. During MRI, the postprandial gastric volume change exceeded the ingested meal volume by 106 ± 12 mL (Mean ± SEM). The HASTE and gradient echo sequences distinguished air from fluid under fasting and postprandial conditions respectively. This postprandial excess mainly comprised air (61 ± 5 mL), which was not significantly different when ingested as 30 or 150 mL aliquots. Fasting and postprandial gastric volumes measured by MRI were generally reproducible within subjects. During SPECT, postprandial volumes increased by 158 ± 18 mL; gastric volumes measured by SPECT were higher than MRI. MRI measures gastric volumes with acceptable performance characteristics; the postprandial excess primarily consists of air, which is not affected by the mode of ingestion. Gastric volumes are technique specific and differ between MRI and SPECT.     

Facilitation of gastric compliance and cardiovascular reaction by repeated isobaric distension of the rat stomach

Gastric distension causes cardiovascular reactions and enhances gastric compliance. Here, we investigated how these responses are related to each other, whether they change upon repeated distension and which neural mechanisms are involved. Mean arterial blood pressure (MAP) in phenobarbital-anaesthetized rats was recorded from a carotid artery and gastric compliance determined with an electronic barostat. Runs of intermittent gastric distension were generated by stepwise increments (5 mmHg) of intragastric (IG) pressure. While gastric compliance peaked at IG pressures of 20 mmHg, the change in MAP (predominantly hypotension) was largest at IG pressures beyond 30 mmHg. Repeated distension enhanced the MAP response to IG pressures beyond 35 mmHg, whereas gastric compliance was facilitated primarily at IG pressures below 20 mmHg. This facilitation of gastric compliance depended on the magnitude of the preceding distension. The MAP response to distension was enhanced by nitric oxide synthase inhibition, inhibited by subdiaphragmatic vagotomy but hardly affected by coeliac ganglionectomy. The facilitation of gastric compliance was changed by vagotomy in a complex manner but left unaltered by the other interventions. These findings show that isobaric gastric distension elicits both MAP and gastric compliance responses whose characteristics, mechanisms and sensitization properties differ profoundly.     

Calcitonin gene-related peptide (CGRP), a potent regulator of biliary flow

This study was designed to investigate the effect of porcine calcitonin gene-related peptide (CGRP) on the motility of the porcine biliary tract in vivo. We measured the pressure in the gallbladder and sphincter of Oddi and, in separate experiments, the biliary flow into the duodenum during local intra-arterial infusions of CGRP. To determine if the observed effect could be caused by release of cholecystokinin (CCK), we measured the CCK release. The basal pressure in the sphincter of Oddi increased dose-dependently from 5.9 ± 0.5 mmHg to 11.5 ± 2.1 mmHg and the motility index of phasic contractions (amplitude × frequency) from 47 ± 8 to 347 ± 64 mmHg s⁻¹, at an infusion rate of 32.6 pmol kg⁻¹ min⁻¹. No effect was observed on the gallbladder pressure. CGRP at 6.5 pmol kg⁻¹ min⁻¹ significantly reduced the biliary flow into the duodenum to 47.7 ± 6% of the basal level. Atropine, injected intravenously, completely abolished the contractile effect of CGRP. CGRP had no effect on the release of CCK.
We conclude that CGRP increases biliary motility and hereby reduces bile flow, an effect which involves cholinergic but not cholecystokininergic mechanisms.     

GABA receptors in the dorsal motor nucleus of the vagus influence feline lower esophageal sphincter and gastric function

Gamma-aminobutyric acid (GABA) antagonist (bicuculline methiodide, BIC; picrotoxin, PIC) or agonist (muscimol, MUS) microinjections were made into the dorsal motor nucleus of the vagus nerve (DMV), and effects on lower esophageal sphincter pressure (LESP), gastric motility, and gastric acid secretion were determined in chloralose-anesthetized cats. Right or left DMV sites were microinjected with BIC, PIC, MUS, or isotonic saline (140 nl) through a glass micropipette having a tip diameter of 15–21 μm. Esophageal body, LESP, and gastric fundic pressures were measured manometrically. Circular smooth muscle contractions of the antrum and pylorus were recorded with strain-gauge force transducers. Gastric acid secretion was measured every 15 min through a gastric cannula and titrated to pH 7.0. DMV microinjection sites were verified histologically. Direct BIC microinjections (0.275 or 0.550 nmol) into the DMV primarily produced a decrease in LESP (71% of all sites tested), with mean LESP changing from 23.2 ± 1.7 mmHg to 3.7 ± 0.7 mmHg (p < 0.01). Tonic LESP increases and phasic LESP contractile activity occurred less frequently. BIC-induced LESP responses were abolished by vagotomy or by microinjections of MUS (0.5 to 10 nmol) into the DMV. Direct PIC microinjection (0.232 nmol) into the DMV produced a pattern of responses similar to those observed with BIC (which were also abolished by vagotomy or by MUS microinjections into the DMV). The antrum and pylorus were also responsive to DMV microinjections of both GABA antagonists. Microinjections of BIC or PIC into the DMV produced increases in gastric circular muscle activity that occurred less frequently than LESP effects, but also were eliminated by vagotomy. The high (0.550 nmol) dose of BIC increased gastric motility significantly more often than the low dose of BIC (p < 0.05). In addition, BIC (0.550 nmol) microinjections into the DMV increased gastric secretary volume (from 0.6 ± 0.2 to 6.0 ± 2.5 ml/15 min; p < 0.01) and total titratible acid (from 34.4 ±8.9 to 86.0 ± 19.1 mEq/15 min; p < 0.01), and decreased gastric pH (from 4.63 ± 0.44 to 3.50 ± 0.49; p < 0.05). Vagotomy also eliminated the gastric secretory effects of DMV BIC. Direct microinjections of MUS into the DMV also blocked BIC- or PIC-induced changes in gastric motility and/or gastric acid secretion. Isotonic saline microinjected into the DMV did not increase basal or decrease stimulated gastric esophageal motility or gastric secretion. These data indicate that LESP, gastric motility, and gastric secretion are influenced by a tonic DMV inhibition mediated by GABA_A receptor stimulation of the DMV. Because disinhibition of these receptors clearly activates the upper gut, future work should focus on identifying the nuclei providing this synaptic input to the DMV that might be involved in the functional regulation of upper gut motor and secretory function.     

Effect of gastrin on proximal gastric motor function in humans

The present study was performed to investigate the effect of gastrin on proximal gastric motor and sensory function. Ten healthy volunteers participated in three experiments performed in random order during: (A) continuous intravenous infusion of saline (control) or (B) gastrin (15 pmol kg-1 h-1) reaching postprandial serum gastrin levels or (C) gastrin infusion (15 pmol kg-1 h-1) preceded by acute acid inhibition with intravenous omeprazole. Proximal gastric function was evaluated using a barostat with stepwise pressure and volume distensions and volume measurements during set pressure (MDP + 2 mmHg). Gastrin significantly increased the intragastric volume compared to control during MDP + 2 mmHg (276 +/- 39 mL vs. 159 +/- 9 mL; P < 0.01) and reduced phasic slow volume wave frequency (from 1.4 +/- 0.1 to 0.7 +/- 0.1 per min; P < 0.01). During isobaric distensions gastrin increased gastric compliance (42 +/- 4 mL mmHg-1 vs. 31 +/- 3 mL mmHg-1; P < 0.05). These effects of gastrin infusion were completely abolished by pretreatment with omeprazole. Symptom perception decreased during gastrin infusion and was more dependent on pressure and wall tension than on volume. In conclusion: gastrin may have a role in regulating proximal gastric mechanics by inducing fundic relaxation and increasing gastric wall compliance. The effect of gastrin is dependent on acid secretion.     

The multi-herbal drug STW 5 (Iberogast®) has prosecretory action in the human intestine

Abstract  There is growing evidence that STW 5 (Iberogast^®, fixed combination of hydroethanolic herbal extracts), besides being effective in functional dyspepsia, also improves symptoms in irritable bowel syndrome (IBS). Clinical data indicate that modulation of mucosal secretion is a promising approach to treat intestinal disorders associated with IBS. We therefore explored the effect of STW 5 on secretion in the human intestine and the mechanisms by which it acts. The Ussing chamber technique was used to measure mucosal secretion in human intestinal mucosa/submucosa preparations and in human epithelial cell line T84. In addition, we recorded STW 5 effects on human enteric neurons with voltage sensitive dye imaging. In human tissue and T84 cells STW 5 induced a dose-dependent increase in ion secretion that was significantly reduced by the Na–K–Cl cotransporter blocker bumetanide, the adenylate cyclase inhibitor MDL-12 330, the non-specific and selective cystic fibrosis transmembrane conductance regulator (CFTR) inhibitors glibenclamide and CFTR_inh-172, respectively, and the blocker of calcium dependent Cl⁻ channels (ClCa) SITS (4-acetamido-4-isothiocyanatostilbene-2,2-disulphonic acid). It was unaffected by amiloride, a blocker of epithelial Na⁺ channels. In human tissue, the nerve blocker tetrodotoxin significantly suppressed the STW 5 response. STW 5 evoked an increased spike discharge in 51% of human submucous neurons. Results suggest that STW 5 is a secretogogue in the human intestine by direct epithelial actions and through activation of enteric neurons. The prosecretory effect is due to increased epithelial Cl⁻ fluxes via CFTR and Ca-dependent ClCa channels. STW 5 may be a novel option to treat secretory disorders associated with IBS and constipation.     

Inhibition of Gastric Motor Function by Circulating Corticotropin-Releasing Factor in Anesthetized Rats

We have investigated the influence of intravenous corticotropin-releasing factor (CRF) on intraluminal pressure of the body of the stomach and the neurohumoral pathways through which CRF inhibits gastric motor function in rats. CRF (0.21–210 pmol) injected intravenously produced a dose-dependent, long-lasting decrease in baseline tone and inhibited phasic gastric contractions measured manometrically in urethane-anesthetized rats. The inhibitory effect of CRF was abolished by administration of hexamethonium or by subdiaphragmatic vagotomy but was unaffected by perineural treatment of the vagus nerves with capsaicin, adrenalectomy, or celiac/superior mesenteric ganglionectomy. Intravenous administration of CRF (126 pmol) inhibited by 69% the emptying of a noncaloric liquid meal as measured by the phenol red technique in conscious rats. Hexamethonium pretreatment significantly attenuated the CRF -induced delay in gastric emptying; bretylium, naloxone, adrenalectomy, and celiac I superior mesenteric ganglionectomy had no such effect. In an isolated tissue preparation, CRF (10⁻¹¹ to 10⁻⁶ M) inhibited spontaneous, but not carbachol-induced, contractions of rat antral longitudinal muscle. The effect of CRF was dose-dependent and abolished in the presence of tetrodotoxin. These results suggest that peripheral CRF-induced inhibition of corpus and antral motor contractility may mediate delayed gastric emptying via an action involving a nicotinic synapse, presumably in the enteric nervous system, that requires a vagal input. The in vitro studies support the concept that the action of CRF is not direct on smooth muscle but involves neural transmission within the enteric nervous system.     

Measurement of gastric emptying by intragastric gamma scintigraphy

Gastric emptying is usually measured in animals and humans by dilution/sampling or external scintigraphy. These methods are either time consuming or require expensive equipment. The capacity of a miniature gamma counter positioned in the stomach to measure emptying of liquid and solid meals was evaluated. In eight conscious pigs fitted with gastric and duodenal cannulae, gastric emptying of saline (500 mL), dextrose (20%, 500 mL), porridge (300 g) and scrambled eggs (300 g), all labelled with 3.5 MBq ^99mTc, was evaluated. When positioned in the antrum the probe was unable to quantify gastric emptying. In contrast, measurements of the fractional emptying of saline over 4-min periods by the probe positioned in the corpus and quantification of radioactivity in the duodenal effluent correlated closely (r = 0.88, P < 0.05). Gastric emptying (50% emptying time) of saline and both solid meals measured by the probe was not significantly different from quantification of the duodenal effluent volume. No difference was observed also for the dextrose meal but only while gastric acid secretion was suppressed by omeprazole. We conclude that an intragastric gamma counter permits measurement of gastric emptying of homogeneous meals provided meal stimulation of gastric secretion was not extensive. This was possible probably by monitoring emptying from the proximal stomach.     

Normal values for the satiety drinking test in healthy children between 5 and 15 years

Abstract  In adults, a slow caloric drinking test has been proposed as a non-invasive tool to estimate gastric accommodation and to quantify meal-induced symptoms in functional dyspepsia (FD). The same test has been proposed for paediatric FD, but normal values are only available for adolescents and adults. The aim of the study was (i) to establish normal values for the satiety drinking test in young children and (ii) to study the influence of demographic factors. In all, 59 healthy children [27 girls; age range 5–16 years, body mass index (BMI) 17.4 ± 2.5 kg m⁻²] were studied in the morning after an overnight fast. They drank a liquid nutrient meal (1.5 kcal mL⁻¹) from beakers that were filled by a peristaltic pump filled at a rate of 15 mL min⁻¹ with. For every 5 min, satiety was scored on a graphic rating scale grade 0–5 (1 = threshold, 5 = maximum), until a score of 5 was reached. Values are given as mean ± SEM and compared by t -test; correlation analysis was performed using Spearman rank test. All children performed the test as indicated except for one 5 years old who stopped prematurely for dislike of the taste. The endpoint was reached at 360 ± 23 mL (540 ± 34 kcal), and was age-dependent (Spearman r  = 0.28, P  = 0.03). No correlation was found between the maximum volume ingested and gender, weight, height or BMI. Age-dependent normal ranges were determined for ages 5–16 at 3-year intervals, and were found to increase with age. We established feasibility of and normal values for a non-invasive satiety drinking test in children with an age range of 5–15 years. This tool can now be used in the assessment of paediatric FD and eating disorders.     

Central regulation of gastric emptying of solid nutrient meals by corticotropin releasing factor

Central regulation of gastric emptying of a solid nutrient meal and spatial and temporal parameters of gastro-pyloro-duodenal contractions by corticotropin-releasing factor (CRF) were investigated in conscious dogs. Intracerebroventricular (ICV) infusion of CRF at 0.033 nmol kg⁻¹ min⁻¹ for 15 min in a volume of 0.2 mL significantly delayed the total gastric emptying time of the meal. ICV infusion of CRF also increased the mean frequency of proximal duodenal contractions and decreased the percentage of distally propagating contractions in the whole duodenum. The remaining parameters of pyloric and duodenal contractions were not affected. A prior ICV infusion of I-helical CRF_9–41 (0.166 nmol kg⁻¹ min⁻¹ for 15 min in a volume of 0.2 mL) blocked the central effects of CRF on gastric emptying time and the duodenal contractions. Central infusion of CRF had no significant effect on the lag phase of gastric emptying. Bilateral truncal vagotomy significantly delayed the gastric emptying time of the solid nutrient meal. However, after vagotomy, ICV infusion of CRF had no effect on gastric emptying time or the spatial and temporal parameters of gastro-pyloro-duodenal contractions. In conclusion, CRF, the mediator of stress response, delays the total gastric emptying time of solid nutrient meals. The delay in gastric emptying may not be due to a change in the spatial and temporal parameters of gastric or pyloric contractions, but mainly due to changes in the parameters of duodenal contractions. The central effects of CRF on gastric emptying and duodenal contractions may be mediated by the vagus nerves.     

Nociceptin/orphanin FQ-induced delay in gastric emptying: role of central corticotropin-releasing factor and glucocorticoid receptors

Abstract  When injected intracerebroventricularly (i.c.v.) in rats, nociceptin/orphanin FQ (N/OFQ) delays gastric emptying and increases plasma corticosterone levels. Our aim in this study was to investigate changes in gastric emptying of a phenol red meal, and the plasma corticosterone response to N/OFQ in adrenalectomized (ADX) rats, in ADX rats injected with corticosterone at 1, 24 and 72 h before the gastric emptying assay, and in intact rats i.c.v. pretreated with a glucocorticoid antagonist (RU486) and with a corticotropin-releasing factor receptor antagonist ( α -helical CRF_9–41). In adrenal intact rats, i.c.v. injection of N/OFQ (2.5 nmol rat⁻¹) significantly delayed gastric emptying (by 70%) and increased plasma corticosterone concentrations. Conversely, in ADX rats, N/OFQ left gastric emptying unchanged. In ADX rats, corticosterone injected at 1, 24 and 72 h before the gastric emptying assay almost restored the N/OFQ-induced delay in gastric emptying. Finally, pretreatment with RU486- and α -helical CRF_9–41 abolished the N/OFQ-induced inhibition of gastric emptying. These findings suggest that central N/OFQ inhibits gastric emptying through an integrated orphaninergic system–CRF interaction in which corticosterone plays a permissive role.     

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.