Pyloric Contractions Research Articles

Physiological characterization of gastric emptying using high-resolution antropyloroduodenal manometry.

Delayed gastric emptying (GE) has been associated with antral and pyloric dysmotility. We aimed to characterize differences in the antral, duodenal, and pyloric motility profiles associated with delayed GE, using high-resolution antropyloroduodenal manometry (HR-ADM). Patients referred for HR-ADM for dyspeptic symptoms performed a concurrent GE breath test (NCT01519180 and NCT04918329). HR-ADM involved 36 sensors 1 cm apart, placed across the pylorus. Interdigestive and postprandial periods were identified. Antral, pyloric, and duodenal motor profiles were analyzed recording the frequency, amplitude, and propagative nature of contractions for each period. Plots of patients with normal and delayed GE were compared. Sixty patients underwent both HR-ADM and GE tests. Twenty-five and 35 patients had delayed and normal GE, respectively. Antral and duodenal motor profiles were not different between the two groups during the interdigestive period. During the postprandial period, a lower frequency of antral contractions was associated with delayed GE (2.22 vs. 1.39 contractions/min; P = 0.002), but no difference in mean contraction amplitude was observed. The pyloric region was identified in all the patients and pylorospasms, defined as 3 min of repeated isolated pyloric contractions, were more frequent in patients with delayed GE (32.0% vs. 5.7%; P = 0.02) during the postprandial period. No difference in duodenal contraction profiles was observed. Manometric profile alterations were observed in 72% of the patients with delayed GE, with 56% having a low frequency of antral contractions. Using HR-ADM, patients with delayed GE displayed different postprandial antropyloric motility as compared with patients with normal GE.NEW & NOTEWORTHY High-resolution antropyloroduodenal manometry (HR-ADM) allows precise characterization of antral, pyloric, and duodenal motility, although its association with gastric emptying (GE) has been poorly investigated. Concurrent HR-ADM with GE measurement showed a lower frequency of antral postprandial contractions and an increased frequency of postprandial pylorospasms in patients with delayed GE. HR-ADM could, therefore, be useful in the future to better select patients for treatments targeting the pylorus.

Comprehensive characterization of antral and pyloric contractions by high resolution manometry: applied physiology in suspected gastroparesis.

Delayed gastric emptying may result from diverse pathophysiological mechanisms including antral hypomotility and pylorospasm. With increasing use of gastric peroral endoscopic myotomy and preliminary evidence of efficacy, our aim was to assess the motor functions of the distal antrum and pylorus in patients with symptoms of gastroparesis using high-resolution antropyloroduodenal manometry (HR-ADM). Sixteen patients with symptoms suggestive of gastroparesis underwent HR-ADM with 13 sensors, 1 cm apart, placed across the antropyloroduodenal (APD) junction and 2 sensors, 10 cm apart, in descending and distal duodenum. The 1-h postprandial motility was quantitated as contraction frequency/minute, average amplitude, and motility index (MI). Six healthy volunteers served as controls. In the patient group, the HR-ADM identified postprandial antral hypomotility, isolated pyloric pressure waves, and tonic elevation of baseline pressure in pylorus. Patients had significantly reduced frequency of the full-hour postprandial antral contractions/minute compared with healthy volunteers [1.52 (0.97, 1.67) vs. 2.04 (1.70, 2.67), P = 0.005], as well as reduced MI [9.65 (8.29, 10.31) vs. 11.04 (10.65, 11.63), P = 0.002]. The average contraction amplitude was numerically, but not significantly reduced [51.9 (21.9, 74.9) vs. 73.0 (59.8, 82.7), P = 0.14]. Bland-Altman plots showed similar distribution of antral contraction frequency and MI during the first and second postprandial 30-min periods for both patients and controls. High-resolution ADM can characterize a variety of postprandial antral contractile and pyloric motility dysfunctions. This technique shows promise to provide guidance for the selection of optimal treatment of patients with gastroparesis.NEW & NOTEWORTHY Current selection of different treatments for patients with gastroparesis is empiric or based on trial and error, though pyloric distensibility and diameter may predict response to pyloric interventions. High-resolution antropyloroduodenal manometry (HR-ADM) can characterize a variety of postprandial antral contractile and pyloric motility dysfunctions in patients with suspected gastroparesis. HR-ADM shows promise to provide guidance for selection and individualization of treatments such as prokinetic agents or pyloric interventions for patients with gastroparesis based on documented pathophysiology.

Effects of a Single Opioid Dose on Gastrointestinal Motility in Rabbits (Oryctolagus cuniculus): Comparisons among Morphine, Butorphanol, and Tramadol

The aim of this study was to evaluate and compare the effects of single doses of butorphanol, morphine, and tramadol on gastrointestinal motility in rabbits (Oryctolagus cuniculus) using non-invasive imaging methods, such as radiographic barium follow through and ultrasonographic contraction counts. Time-lapse radiographic and ultrasound examinations were performed before and after a single intramuscular dose of 5 mg kg−1 butorphanol, 10 mg kg−1 morphine, or 10 mg kg−1 tramadol. Pyloric and duodenal contraction counts by ultrasonography and radiographic repletion scores for the stomach and caecum were analysed using a mixed linear model. No significant effect was noted on ultrasound examinations of pyloric and duodenal contractions after administration of an opioid treatment. Morphine had a significant effect on the stomach and the caecum repletion scores, whereas butorphanol had a significant effect only on the caecum repletion score. Tramadol had no significant effect on the stomach or caecum repletion scores. The present findings suggest that a single dose of 5 mg kg−1 butorphanol or 10 mg kg−1 morphine temporarily slows gastrointestinal transit in healthy rabbits, preventing physiological progression of the alimentary bolus without the induction of ileus. In contrast, a single dose of 10 mg kg−1 tramadol has no such effects.

Luminal Chemoreceptors and Intrinsic Nerves: Key Modulators of Digestive Motor Function.

This chapter reviews data on the pathways by which luminal, mainly duodenal, chemoreceptors modulate gastro-pyloro-duodenal motor function to control emptying of nutrients into the small intestine. The vagus mediates proximal gastric relaxation caused by nutrient stimulation of duodenal/jejunal mucosal chemoreceptors. Modulation of the spatial patterning and inhibition of antral contractions during duodenal chemoreceptor activation are somewhat conflicting: both vagal control and ascending intramural nerves appear to play a role. Intraduodenal nutrients stimulate the localized pyloric contractions that prevent transpyloric flow via ascending duodenal intramural nerve pathways. Though not yet formally investigated, patterns of activation of the duodenal brake motor mechanism suggest that duodenal loop mucosal chemoreceptors signal to a brake mechanism at the most aborad region of the duodenum via descending intramural duodenal nerves.Intrinsic intramural pathways are important in the control of the first stages of digestion.

S3596 Chronic Abdominal Pain After Gastrojejunostomy: An Unexpected Outcome

INTRODUCTION: Gastroparesis is a neuromuscular disorder of the upper gastrointestinal (UGI) tract. Diabetes is the most common known etiology, accounting for 20–30% of cases. Other major causes include medication adverse effects, neuromuscular disease, idiopathic, and post-surgical gastroparesis (PSG), which has a prevalence of 0.4-5%. We present a case of PSG treated with botulinum toxin (Botox). CASE DESCRIPTION/METHODS: A 56-year-old man with uncontrolled diabetes (HbA1c 14.2), hypertension, and small bowel perforation status post gastrojejunostomy in 2014 presented with nausea, vomiting, and diffuse postprandial abdominal pain. Initial medical management with pro-motility agents: erythromycin and metoclopramide were unsuccessful. CT scan abdomen was negative for acute pathology. EGD revealed a patent gastrojejunostomy with normal pyloric contractions. No retained food, ulcer, or gastritis was found. A gastric emptying study was negative for gastroparesis, showing a functional gastrojejunostomy. The patient underwent EGD with Botox injection into the pylorus and gastrojejunal anastomosis (Figures 1 and 2). He was also started on low dose nortriptyline. He remained symptoms free at 2 months follow up. DISCUSSION: PSG is thought to have a multifactorial etiology including dysfunction of the parasympathetic system after vagotomy and lack of duodenal motilin release after duodenal resection. After one year, a significant percentage of patients develop compensatory neurostimulation to adapt to their new anatomy. Gastrojejunostomy predisposes to slow emptying from the gastric remnant and delayed transit in the denervated efferent limb. Therefore, less than 25 cm resection is often recommended to avoid stasis. Botox injection for refractory PSG has some evidence of efficacy. One trial showed an average response rate of 43% for 5 months, with a target on quality of life. Whereas another demonstrated a 55% improvement at 6 weeks post-procedure with positive outcomes in the motility of solid food. Additionally, non-selective serotoninergic inhibitors (NSRI) such as nortriptyline (with the least anticholinergic effect) have shown promising effects at low doses for patients with refractory gastroparesis. Our patient likely had a combination of diabetic gastroparesis and PSG, which did not respond to medical therapy. We demonstrate the effective use of botulinum injection in combination with NSRI.Figure 1.: Pylorus, blood is seen post Botox injection.Figure 2.: Patent gastrojejunostomy and antrum.

Impact of gastric per-oral endoscopic myotomy on static and dynamic pyloric function in gastroparesis patients.

Functional Lumen Imaging Probe (EndoFLIP) tests typically measure static pyloric parameters, but the pylorus exhibits phasic variations on manometry. Dynamic changes in pyloric function have not been quantified using EndoFLIP, and the impact of Gastric Per-Oral Endoscopic Myotomy (G-POEM) on static and dynamic pyloric activity in gastroparesis is unknown. EndoFLIP balloon inflation to 30, 40, and 50mL was performed to measure mean, maximum, and minimum values and variability in pyloric diameter and distensibility before and after G-POEM in 20 patients with refractory gastroparesis. The impact of phasic contractions on these pyloric measures was compared. G-POEM increased mean (P<.0001) and maximum (P=.0002) pyloric diameters and mean (P=.02) and maximum (P=.02) pyloric distensibility on 50mL EndoFLIP inflation but not intraballoon pressures or minimum diameters or distensibility. Temporal variability of pyloric diameter (P=.02) and distensibility (P=.02) also increased after G-POEM. Phasic coupled contractions propagating from the antrum through the pylorus were observed in 37.5% of recordings; other phasic activity including isolated pyloric contractions were seen in 23.3%. Variability of pyloric diameter and distensibility tended to be higher during recordings with phasic activity. Some pyloric responses to G-POEM were influenced by age, gastroparesis etiology, gastric emptying, and prior botulinum toxin injection. Pyloric activity exhibits dynamic changes on EndoFLIP testing in gastroparesis. G-POEM increases maximal but not minimal diameter and distensibility with increased variations, suggesting this therapy enhances pyloric opening but may not impair pyloric closure. Phasic pyloric contractions contribute to variations in pyloric activity.

Clinical value of three-dimensional ultrasound VOCAL in evaluation of gastric emptying function in children with functional dyspepsia

Objective To evaluate the clinical value of three-dimensional ultrasound VOCAL technique in evaluating gastric emptying function in children with functional dyspepsia (FD). Methods Seventy-one children with FD who were treated in Wenzhou Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine from January 2018 to June 2018 were enrolled as the study subjects (observation group), and 71 normal children without FD were selected as controls (control group). The gastric emptying, antral pyloric systolic contraction frequency and distal gastric contraction movement in different time groups were analyzed, and GET1/2 and 2h gastric residual situation before and after treatment in the observation group were compared. Results The GET1/2 of the observation group was (60.2±12.69)min, and the gastric emptying rate of the observation group was (61.9±12.2)min and (72.0±12.3)min at 90min and 120min, which were significantly better than those of the control group, and the differences were statistically significant (t=19.092, 15.092, 14.882, P=0.016, 0.024, 0.033). The frequency of antral pyloric systolic contraction, gastric antrum contraction frequency and gastric antrum contraction amplitude were (1.1±0.7)times/min, (2.9±0.8)times/min, (1.0±0.6)cm, respectively.Compared with the control group, the differences were statistically significant (t=16.092, 21.224, 8.092, all P<0.05). In the observation group of 71 children: GET1/2 before treatment and after treatment were (68.1±11.8)min, (54.2±9.8)min, respectively.The gastric residual at 2h after treatment was (31.2±8.0)%, (22.1±7.0)%, respectively.The GET1/2 and 2h gastric residual rate of the children were significantly lower than before treatment, and the differences were statistically significant (t=18.983, 21.004, all P<0.05). Conclusion Three-dimensional ultrasound VOCAL technology can be used as an evaluation standard for FD in children. Key words: Dyspepsia; Ultrasonography; Three-dimensional ultrasound technology; Gastric emptying

Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal-dependent mechanisms.

The gut-brain peptide neuromedin U (NMU) decreases food intake and body weight and improves glucose tolerance. Here, we characterized NMU as an enteropeptide and determined how it impacts glucose excursion. NMU was expressed predominantly in the proximal small intestine, and its secretion was triggered by ingestion of a mixed meal. Although a single peripheral injection of NMU in C57BL/6NRj mice prevented the rise of glycemia upon an oral but not an intraperitoneal load of glucose, it unexpectedly prevented insulin secretion, only slightly improved peripheral insulin sensitivity, and barely reduced intestinal glucose absorption. Interestingly, peripheral administration of NMU abrogated gastric emptying. NMU receptors 1 and 2 were detected in pyloric muscles and NMU was able to directly induce pyloric contraction in a dose-dependent manner ex vivo in isometric chambers. Using a modified glucose tolerance test, we demonstrate that improvement of oral glucose tolerance by NMU was essentially, if not exclusively, because of its impact on gastric emptying. Part of this effect was abolished in vagotomized (VagoX) mice, suggesting implication of the vagus tone. Accordingly, peripheral injection of NMU was associated with increased number of c-FOS-positive neurons in the nucleus of the solitary tract, which was partly prevented in VagoX mice. Finally, NMU kept its ability to improve oral glucose tolerance in obese and diabetic murine models. Together, these data demonstrate that NMU is an enteropeptide that prevents gastric emptying directly by triggering pylorus contraction and indirectly through vagal afferent neurons. This blockade consequently reduces intestinal nutrient absorption and thereby results in an apparent improved tolerance to oral glucose challenge.-Jarry, A.-C., Merah, N., Cisse, F., Cayetanot, F., Fiamma, M.-N., Willemetz, A., Gueddouri, D., Barka, B., Valet, P., Guilmeau, S., Bado, A., Le Beyec, J., Bodineau, L., Le Gall, M. Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal-dependent mechanisms.

Influence of a single dose of buprenorphine on rabbit (Oryctolagus cuniculus) gastrointestinal motility

ObjectiveTo establish a noninvasive imaging protocol for rabbit gastrointestinal transit evaluation. To assess the effect of a single injection of buprenorphine on the digestive transit of rabbits via this new technique. Study designProspective, parallel study. AnimalsFifteen specific pathogen-free male New Zealand White rabbits weighing 2.68 ± 0.28 kg. MethodsA 10 mL kg–1 barium meal was administered and the rabbits were subjected to serial radiographic and ultrasound examinations without treatment and 1 week later following a single intramuscular dose of 100 μg kg–1 of buprenorphine. Radiographic data from the stomach and caecum were collected and assigned a retention score ranging from 0 (no barium) to 3 (large amount of barium). The resulting scores and pyloric and duodenal contraction counts were analysed using a mixed linear model and are expressed as least square mean (lsm) ± standard error. Transit was estimated based on the apparition time of faeces in the pelvic area and analysed using a Wilcoxon test. A p < 0.05 was considered significant. ResultsBuprenorphine treatment induced a higher lsm number of pyloric (1.73 ± 0.19 versus 0.78 ± 0.19, p < 0.01) and lsm duodenal contractions (17.35 ± 1.04 versus 13.44 ± 1.04, p < 0.01). Buprenorphine administration decreased the lsm barium retention score in the stomach (2.44 ± 0.05 versus 2.64 ± 0.05, p < 0.01), but had no effect on the lsm barium retention score in the caecum. The time to apparition of faeces in the pelvic area was not influenced by buprenorphine administration (p = 0.66). Conclusions and clinical relevanceA single high dose of buprenorphine appears to have no adverse effect on gastrointestinal motility in healthy rabbits.

Dual autonomic inhibitory action of central Apelin on gastric motor functions in rats.

Centrally administered apelin has been shown to inhibit gastric emptying (GE) in rodents, however, the relevant mechanism has been investigated incompletely. Using male Wistar rats, we investigated the efferent pathways involved in gastroinhibitory action of central apelin. Stereotaxic intracerebroventricular (icv) cannulation, subdiaphragmatic vagotomy (VGX) and/or celiac ganglionectomy (CGX) were performed 7 days prior to the experiments. Apelin-13 was administered (30 nmol, icv) 90 min prior to GE measurement. Nitric oxide synthase inhibitor L-NAME (100 mg/kg), sympatholytic agent guanethidine (5 mg/kg) and/or muscarinic receptor agonist bethanechol (1 mg/kg) were administered intraperitoneally 30 min prior to the central apelin-13 injection. Two strain gages were implanted serosally onto antrum and pylorus to monitor gastric postprandial motility. Heart rate variability (HRV) analysis was performed before and after central vehicle or apelin-13 administration. Apelin-13 delayed solid GE significantly by disturbing coordinated antral and pyloric postprandial contractions. The apelin-induced delayed GE was attenuated partially by CGX or VGX, whereas it was restored completely in rats underwent both CGX and VGX. L-NAME did not change the apelin-induced alterations. Guanethidine or bethanechol restored the apelin-induced gastroinhibition partially, while it was abolished completely in rats received both agents. Apelin-13 decreased the HRV spectral activity in high-frequency range by increasing low-frequency component and the ratio of LF:HF. The present data suggest that (1) both vagal parasympathetic and sympathetic pathways play a role in apelin-induced gastroinhibition, (2) central apelin attenuates vagal cholinergic pathway rather than activating nonadrenergic-noncholinergic pathway. Apelin/APJ receptor system might be candidate for the treatment of autonomic dysfunction and gastrointestinal motor disorders.

The Cause of Pyloric Stenosis of Infancy: Primary Hyperacidity and Biochemistry Combined

The cause of pyloric stenosis (PS) of infancy is at present unknown. A theory of causation is proposed, which is consistent with all the known clinical features of this condition. It is based on the knowledge that babies with PS are hypersecretors of acid, which predates the development of PS and is an inherited constitutional feature. This acidity becomes dangerously high due to a temporary insensitivity of the negative feedback between gastrin and gastric acidy within the first few weeks of life. Normal babies with normal acidity levels will also experience peak acidity at that time but not dangerously so. Acid entering the duodenum causes contraction of the pyloric sphincter. Hyperacidity will naturally lead to repeated pyloric sphincter contractions with resulting work hypertrophy of the sphincter and PS. Should the baby with PS survive beyond the age of approximately 6 weeks, the matured negative feedback between gastrin and acid will ensure that dangerous hyperacidity is kept in check. Thus, the passage of time allows the physiological control of hyperacidity. When associated with an age-related widening of the pyloric canal control, a long-term cure is the natural outcome. This theory explains satisfactorily all the known and hitherto unexplained features of this condition.

Inhibitory Effects of Botulinum Toxin Type A on Pyloric Cholinergic Muscle Contractility of Rat.

Botulinum toxin type A (BTX-A) selectively cleaves synaptosomal-associated protein of 25 kDa (SNAP-25) and results in inhibition of the fusion of synaptic vesicles containing neurotransmitters with the presynaptic membrane to undergo exocytosis and release. The aim of this study was to investigate whether BTX-A inhibited the pyloric smooth muscle contractility induced by acetylcholine (ACh) after BTX-A-mediated cleavage of SNAP-25 antagonized by toosendanin (TSN). Three groups of rat pyloric muscle strips were studied in vitro. All strips were allowed to equilibrate for 52 min under a basal loading tension of 1 g in Krebs solution and spontaneous contractile waves were recorded as their own controls before adding each drug. According to experimental protocols, 100 μM ACh, 1 μM atropine, 29.6 μM TSN and 10 U/ml BTX-A was added, respectively. BTX-A directly inhibited pyloric spontaneous contraction and ACh-induced contractile response. Addition of 10 U/ml BTX-A still inhibited pyloric smooth muscle contractility following incubation of TSN, while subsequent administration of 100 μM ACh had no effect. BTX-A inhibits pyloric smooth muscle contractility in our study suggesting BTX-A inhibits not only ACh release from cholinergic nerves but also muscarinic cholinergic muscular transmission.

Does magnetically assisted capsule endoscopy improve small bowel capsule endoscopy completion rate? A randomised controlled trial.

Background and study aims: Delayed gastric emptying is a significant factor in incomplete small bowel capsule examinations. Gastric transit could be hastened by external magnetic control of the capsule. We studied the feasibility of this approach to improve capsule endoscopy completion rates. Patients and methods: Prospective, single-center, randomized controlled trial involving 122 patients attending for small bowel capsule endoscopy using MiroCam Navi. Patients were randomized to either the control group (mobilisation for 30 minutes after capsule ingestion, followed by intramuscular metoclopramide 10 mg if the capsule failed to enter the small bowel) or the intervention group (1000 mL of water prior to capsule ingestion, followed by positional change and magnetic steering). Outcome measures were capsule endoscopy completion rate, gastric clarity and distention, relationship of body habitus to capsule endoscopy completion rate (CECR), and patient comfort scores. Results: 122 patients were recruited (61 each to the control and intervention groups: mean age 49 years [range 21 – 85], 61 females). There was no significant difference in CECR between the two groups (P = 0.39). Time to first pyloric image was significantly shorter in the intervention group (P = 0.03) but there was no difference in gastric transit times (P = 0.12), suggesting that magnetic control hastens capsular transit to the gastric antrum but does not influence duodenal passage. Gastric clarity and distention were significantly better in the intervention group (P < 0.0001 and P < 0.0001 respectively). Conclusions: Magnetic steering of a small bowel capsule is unable to overcome pyloric contractions to enhance gastric emptying and improve capsule endoscope completion rate. Excellent mucosal visualisation within the gastric cavity suggests this technique could be harnessed for capsule examination of the stomach.

The cause of pyloric stenosis of infancy: A hyperacidity pathogenesis

The cause of pyloric stenosis of infancy (PS) is at present unknown.A theory of causation is proposed which is consistent with all the known clinical features of this condition.It is based on the knowledge that PS babies are hypersecretors of acid which pre-dates the development of PS and is an inherited constitutional feature. This acidity will become temporarily and dangerously high due to an insensitivity of the negative feed-back between gastrin and gastric acidy within the first few weeks of life. Normal babies who have inherited normal acidity will also experience peak acid secretions at that time but will be much less acid than babies destined to develop PS.Acid entering the duodenum causes contraction of the pyloric sphincter. Hyperacidity will naturally lead to repeated pyloric sphincter contractions and sphincter hypertrophy. Inappropriate repeated feeding of the vomiting PS baby by a first-time overanxious mother to her ever hungry baby, by provoking feed related sphincter contraction is considered to play a significant part in pathogenesis.Should the baby with PS survive beyond the age of around 6weeks, the matured negative feed-back between gastrin and acid will ensure that dangerous hyperacidity is kept in check. This coupled with the natural pyloric canal widening with age, will lead then to an long lasting cure.This theory explains satisfactorily all the known and hitherto unexplained features of this condition.

PWE-028 Randomised comparison of a standard protocol using metoclopramide versus a hand held magnet to enhance gastric emptying of the small bowel capsule

<h3>Introduction</h3> Delayed gastric emptying can be a significant factor in incomplete small bowel capsule endoscopy (SBCE). This has been addressed by using prokinetic agents, albeit with the need for cannulation or intramuscular (IM) injections and the small risk of adverse drug reactions. Recently a manoeuvrable small bowel (SB) capsule has become available using a handheld magnet to control movement. We compared this magnetically steerable method to a standard protocol using metoclopramide for enhancing gastric transit of the SB capsule. <h3>Method</h3> Single centre, randomised controlled trial involving 121 patients attending for SBCE using MiroCam Navi (Intromedic, Seoul, Korea). Patients were randomised to either the standard (control) group or the steerable capsule (intervention) group. The control group were mobilised for 30 min after ingestion of the capsule, followed by IM metoclopramide 10 mg if the SBCE had failed to enter the SB. The intervention group ingested a gastric distention volume of 1000 mls of water with 5 drops of simethicone prior to SBCE. Positional change and magnetic steering was used to manipulate the SBCE into the duodenum. If unsuccessful after 30 min, the patient transferred to the standard protocol. 60 patients per group were required to achieve 80% power, assuming a completion rate of 70% for the control protocol, improving to 90% with the intervention. Ethics: 13/YH/0358. <h3>Results</h3> 121 patients were recruited (60 to the control group, 61 to the intervention group: mean age 49 years (range 21–85), 61 females). 2 patients were excluded due to gastric retention of the capsule. Mobility, particularly tilting and rotational movements was achieved with reasonable precision in the gastric cavity. However, this became challenging in the pre-pyloric region due to variability in anatomical orientation and peristaltic contractions. Clarity of gastric mucosal views was excellent. Gastric transit time (GTT) was longer in the intervention group but this did not reach statistical significance (median 23 vs 51 min Mann-Whitney U=1487, p = 0.116). There was no significant difference in capsule endoscopy completion rate (CECR) between the two groups (χ² p = 0.395). Examining the intervention sub-group: no correlation between body mass index (BMI) or waist-hip ratio (WHR) and GTT was demonstrated (r = 0.002 and r = 5.98 respectively). Similarly no significant difference between WHR (p = 0.938) or BMI (p = 0.507) and CECR was noted. <h3>Conclusion</h3> Magnetic steering of a SB capsule is unable to overcome pyloric contractions to enhance gastric emptying. However, mobility and image clarity within the gastric cavity was excellent, Therefore, with further improvements this technique could potentially be harnessed to enable capsular examination of the gastric cavity. <h3>Disclosure of interest</h3> None Declared.

Infantile hypertrophic pyloric stenosis (IHPS): a study of its pathophysiology utilizing the newborn hph-1 mouse model of the disease.

Infantile hypertrophic pyloric stenosis (IHPS) is a common disease of unknown etiology. The tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia-1 (hph-1) newborn mouse has a similar phenotype to the human condition. For hph-1 and wild-type control animals, pyloric tissue agonist-induced contractile properties, reactive oxygen species (ROS) generation, cGMP, neuronal nitric oxide synthase (nNOS) content, and Rho-associated protein kinase 2 (ROCK-2) expression and activity were evaluated. Primary pyloric smooth muscle cells from wild-type newborn animals were utilized to evaluate the effect of BH4 deficiency. One-week-old hph-1 mice exhibited a fourfold increase (P < 0.01) in the pyloric sphincter muscle contraction magnitude but similar relaxation values when compared with wild-type animals. The pyloric tissue nNOS expression and cGMP content were decreased, whereas the rate of nNOS uncoupling increased (P < 0.01) in 1-wk-old hph-1 mice when compared with wild-type animals. These changes were associated with increased pyloric tissue ROS generation and elevated ROCK-2 expression/activity (P < 0.05). At 1-3 days of age and during adulthood, the gastric emptying rate of the hph-1 mice was not altered, and there were no genotype differences in pyloric tissue ROS generation, nNOS expression, or ROCK-2 activity. BH4 inhibition in pyloric smooth muscle cells resulted in increased ROS generation (P < 0.01) and ROCK-2 activity (P < 0.05). Oxidative stress upregulated ROCK-2 activity in pyloric tissue, but no changes were observed in newborn fundal tissue in vitro. We conclude that ROS-induced upregulation of ROCK-2 expression accounts for the increased pyloric sphincter tone and nNOS downregulation in the newborn hph-1 mice. The role of ROCK-2 activation in the pathogenesis of IHPS warrants further study.

Effects of acclimation and acute temperature change on specific dynamic action and gastric processing in the green shore crab, Carcinus maenas

The effects of temperature acclimation and acute temperature change were investigated in postprandial green shore crabs, Carcinus maenas. Oxygen uptake, gut contractions and transit rates and digestive efficiencies were measured for crabs acclimated to either 10°C or 20°C and subsequently exposed to treatment temperatures of 5, 15, or 25°C. Temperature acclimation resulted in a partial metabolic compensation in unfed crabs, with higher oxygen uptake rates measured for the 10°C acclimated group exposed to acute test temperatures. The Q10 values were higher than normal, probably because the acute temperature change prevented crabs from fully adjusting to the new temperature. Both the acclimation and treatment temperature altered the characteristics of the specific dynamic action (SDA). The duration of the response was longer for 20°C acclimated crabs and was inversely related to the treatment temperature. The scope (peak oxygen consumption) was also higher for 20°C acclimated crabs with a trend towards an inverse relationship with treatment temperature. Since the overall SDA (energy expenditure) is a function of both duration and scope, it was also higher for 20°C acclimated crabs, with the highest value measured at the treatment temperature of 15°C. The decline in total SDA after acute exposure to 5 and 25°C suggests that both cold stress and limitations to oxygen supply at the temperature extremes could be affecting the SDA response. The contractions of the pyloric sac of the foregut region function to propel digesta through the gut, and contraction rates increased with increasing treatment temperature. This translated into faster transit rates with increasing treatment temperatures. Although pyloric sac contractions were higher for 20°C acclimated crabs, temperature acclimation had no effect on transit rates. This suggests that a threshold level in pyloric sac contraction rates needs to be reached before it manifests itself on transit rates. Although there was a correlation between faster transit times and the shorter duration of the SDA response with increasing treatment temperature, transit rates do not make a good proxy for calculating the SDA characteristics. The digestive efficiency showed a trend towards a decreasing efficiency with increasing treatment temperature; the slower transit rates at the lower treatment temperatures allowing for more efficient nutrient absorption. Even though metabolic rates of 10°C acclimated crabs were higher, there was no effect of acclimation temperature on digestive efficiency. This probably occurred because intracellular enzymes and digestive enzymes are modulated through different control pathways. These results give an insight into the metabolic and digestive physiology of Carcinus maenas as it makes feeding excursions between the subtidal and intertidal zones.

W2041 Effects of the Nitric Oxide (NO) Synthase Inhibitor, NG-Nitro-L-Arginine-Methyl-Ester (L-NAME), On Delayed Gastric Emptying Induced By Hyperglycaemia in Healthy Humans

Acute hyperglycaemia slows gastric emptying, reduces proximal gastric tone, inhibits antral motility, and stimulates pyloric contractions. The mechanisms mediating these effects are unknown, but nitric oxide (NO), a key inhibitory neurotransmitter in the gut, could potentially be involved. Aim: To determine whether the NO synthase inhibitor, L-NAME, reverses the effects of hyperglycaemia on gastric emptying and proximal and distal gastric motility. Methods: Seven healthy volunteers (4 male; age 30.3±3.8 yr; BMI 23.6±1.2 kg/m2) were studied in a 4-way randomised crossover design (hyperglycaemia vs. euglycaemia; L-NAME vs. placebo) after an overnight fast. After positioning a transnasal manometry catheter across the pylorus, the blood glucose was maintained at either 15 mmol/L or 5 mmol/L using a glucose/insulin clamp. Once the blood glucose was stabilised for 30 min, an intravenous infusion of L-NAME (180 mcg/kg/h) or placebo (0.9% saline) was commenced (t = 0) and continued for 150 min. At t = 30, subjects ingested a test drink containing 50g glucose made up to 300ml with water. Gastric emptying and intragastric distribution (proximal and distal stomach retention) were measured using 3-D ultrasound. Antropyloroduodenalmotility was recorded concurrently. Statistical analysis was performed using repeated measures ANOVA. Data presented as mean ± SEM. Results: Gastric half-emptying time (T50) was prolonged on the hyperglycaemia/placebo day compared to the remaining 3 study days, which were no different from each other (127±19min [hyperglycaemia/placebo] vs. 86±7min [hyperglycaemia/L-NAME] vs. 77±12min [euglycaemia/placebo] vs. 81±5min [euglycaemia/ L-NAME]; P = 0.01). The effect of hyperglycaemia on gastric emptying was completely abolished by L-NAME. The rate of total gastric emptying closely correlated to that of proximal (r = 0.970; P < 0.0001), but not distal (P = N.S.), gastric emptying. Fasting antral motility index was suppressed during hyperglycaemia (P < 0.05). Basal pyloric pressure was increased during hyperglycaemia (P < 0.001), and decreased with L-NAME (P < 0.001). Conclusions: Hyperglycaemia-induced delay in gastric emptying is associated with increased proximal retention and increased basal pyloric pressure; these effects are attenuated markedly by L-NAME.

Inhibitory effects and mechanisms of intestinal electrical stimulation on gastric tone, antral contractions, pyloric tone, and gastric emptying in dogs

The aim of this study was to investigate the effects and mechanisms of intestinal electrical stimulation (IES) on gastric tone, antral and pyloric contractions, and gastric emptying in dogs. Female hound dogs were equipped with a duodenal or gastric cannula, and one pair of serosal electrodes was implanted in the small intestine. The study consisted of five different experiments. Liquid gastric emptying was assessed by collection of chyme from the duodenal cannula in a number of sessions with and without IES and with and without N-nitro-l-arginine (l-NNA). Postprandial antral and pyloric contractions were measured with and without IES and in the absence and presence of l-NNA or phentolamine by placement of a manometric catheter into the antrum and pylorus via the duodenal cannula. Gastric tone was assessed by measurement of gastric volume at a constant pressure. Gastric emptying was substantially and significantly delayed by IES or l-NNA compared with the control session. IES-induced delay of gastric emptying became normal with addition of l-NNA. IES reduced gastric tone, which was blocked by l-NNA. IES also inhibited antral contractions (frequency and amplitude), and this inhibitory effect was not blocked by l-NNA but was blocked by phentolamine. IES alone did not affect pyloric tone or resistance, but IES + l-NNA decreased pyloric tone. In conclusion, IES reduces gastric tone via the nitrergic pathway, inhibits antral contractions via the adrenergic pathway, does not affect pyloric tone, and delays liquid gastric emptying. IES-induced delay of gastric emptying is attributed to its inhibitory effects on gastric motility.

Gastric processing in the Dungeness crab, Cancer magister, during hypoxia

The gastric physiology of the Dungeness crab, Cancer magister, was investigated over a range of oxygen tensions. Postprandial crabs reacted differently to hypoxia compared with unfed animals. The bradycardic response in postprandial animals was reduced, suggesting a summation of responses with feeding. A similar pattern was observed for ventilation rate. In unfed animals ventilation rate increased slightly as oxygen levels declined, but dropped significantly in oxygen tensions below 3.2 kPa, whereas in postprandial crabs it increased significantly in the lower oxygen regimes. Gastric processing of the meal was followed using a fluoroscope. Pyloric contraction rates were maintained during mild hypoxia, but decreased in 5.3 kPa oxygen tension and below. This led to an increase in clearance times of digesta from the foregut, midgut and hindgut regions. The slowing of gastric processing in the lower oxygen tensions suggested that the animals were unable to maintain their internal oxygen concentration. A significant reduction in efficiency of assimilation only occurred in the lowest oxygen regime tested (1.6 kPa). The range of hypoxia where gastric processing was affected corresponded closely to the levels of oxygen that modulate the foraging behaviour of C. magister. By using both physiological and behavioural mechanisms C. magister can maintain digestive processes, even in severely oxygen depleted environments.