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.

Functional and anatomical gastric regions and their relations to motility control.

The common occurrence of gastric disorders, the accelerating emphasis on the role of the gut-brain axis, and development of realistic, predictive models of gastric function, all place emphasis on increasing understanding of the stomach and its control. However, the ways that regions of the stomach have been described anatomically, physiologically, and histologically do not align well. Mammalian single compartment stomachs can be considered as having four anatomical regions fundus, corpus, antrum, and pyloric sphincter. Functional regions are the proximal stomach, primarily concerned with adjusting gastric volume, the distal stomach, primarily involved in churning and propelling the content, and the pyloric sphincter that regulates passage of chyme into the duodenum. The proximal stomach extends from the dome of the fundus to a circumferential band where propulsive waves commence (slow waves of the pacemaker region), and the distal stomach consists of the pacemaker region and the more distal regions that are traversed by waves of excitation, that travel as far as the pyloric sphincter. Thus, the proximal stomach includes the fundus and different extents of the corpus, whereas the distal stomach consists of the remainder of the corpus and the antrum. The distributions of aglandular regions and of specialized glands, such as oxyntic glands, differ vastly between species and, across species, have little or no relation to anatomical or functional regions. It is hoped that this review helps to clarify nomenclature that defines gastric regions that will provide an improved basis for drawing conclusions for different investigations of the stomach.

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.

Deciphering Stomach Myoelectrical Slow Wave Conduction Patterns via Confocal Imaging of Gastric Pacemaker Cells and Fractal Geometry.

Interstitial Cells of Cajal (ICC) are specialized gastrointestinal (GI) pacemaker cells that generate and actively propagate slow waves of depolarization (SWs) of the muscularis propria. SWs regulate the motility of the GI tract necessary for digestion, absorption of nutrients, and elimination of waste. Within the gastric wall, there are three main inter-connected layers of ICC networks: longitudinal muscle ICC (ICC-LM), myenteric plexus ICC (ICC-MP) & circumferential muscle (ICC-CM). Fractal structural parameters such as Fractal Dimension (FD), Lacunarity and Succolarity, have many advantages over physically-based parameters when it comes to characterizing the complex architectures of ICC networks. The analysis of networks of ICC throughout the proximal and distal murine gastric antrum with the FD and Lacunarity metrics was previously performed. Although the application of Succolarity is relatively nascent compared to the FD and Lacunarity; nevertheless, numerous studies have demonstrated the capability of this fractal measure to extract information from images associated with flow by which neither the FD nor Lacunarity are capable of discerning. In this study, Succolarity analysis of ICC-MP and ICC-CM networks were performed with confocal images taken across the proximal and distal murine antrum. Our findings demonstrated the Succolarity of ICC-MP and ICC-CM varied with directions and antral regions. The Succolarity of ICC-MP did not vary considerably with direction, however, Succolarity was higher in the aboral direction with 0.2113 ±0.1589, and 0.0637 ±0.0822 in the proximal and distal antrum, respectively. The overall Succolarity of ICC-MP was significantly higher than that of ICC-CM in the proximal antrum ( 0.1580±0.1325 vs [Formula: see text]) and in the distal antrum ( 0.0449 ±0.0409 vs [Formula: see text]). Clinical Relevance-Modeling SWs conduction patterns via image analysis of detailed ICC networks help to facilitate an improved understanding of the mechanisms underpinning GI myoelectric activity and the diseases associated with its dysfunction.

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.

The three muscle layers in the pyloric sphincter and their possible function during antropyloroduodenal motility.

This study was conducted to determine the muscular arrangement of the human pyloric sphincter using a comprehensive approach that involved microdissection, histology, and microcomputed tomography (micro-CT). The stomachs of 80 embalmed Korean adult cadavers were obtained. In all specimens, loose muscular tissue of the innermost aspect of the sphincter wall ran aborally, forming the newly found inner longitudinal muscle bundles, entered the duodenum, and connected with the nearby circular bundles. In all specimens, approximately one-third of the outer longitudinal layer of the sphincter entered its inner circular layer, divided the circular layer into several parts, and finally connected with the circular bundles. Anatomical findings around the sphincter were confirmed in micro-CT images. The sphincter wall comprised three layers: an inner layer of longitudinal bundles, a middle layer of major circular and minor longitudinal bundles, and an outer layer of longitudinal bundles. The stomach outer longitudinal bundles were connected to the sphincter circular bundles. The inner longitudinal bundles of the sphincter were connected to the adjacent circular bundles of the duodenum.

Measurement of fasted state gastric antral motility before and after a standard bioavailability and bioequivalence 240 mL drink of water: Validation of MRI method against concomitant perfused manometry in healthy participants.

OBJECTIVE: The gastrointestinal environment in which drug products need to disintegrate before the drug can dissolve and be absorbed has not been studied in detail due to limitations, especially invasiveness of existing techniques. Minimal in vivo data is available on undisturbed gastrointestinal motility to improve relevance of predictive dissolution models and in silico tools such as physiologically-based pharmacokinetic models. Recent advances in magnetic resonance imaging methods could provide novel data and insights that can be used as a reference to validate and, if necessary, optimize these models. The conventional method for measuring gastrointestinal motility is via a manometric technique involving intubation. Nevertheless, it is feasible to measure gastrointestinal motility with magnetic resonance imaging. The aim of this study was is to develop and validate a magnetic resonance imaging method using the most recent semi-automated analysis method against concomitant perfused manometry method. MATERIAL AND METHODS: Eighteen healthy fasted participants were recruited for this study. The participants were intubated with a water-perfused manometry catheter. Subsequently, stomach motility was assessed by cine-MRI acquired at intervals, of 3.5min sets, at coronal oblique planes through the abdomen and by simultaneous water perfused manometry, before and after administration of a standard bioavailability / bioequivalence 8 ounces (~240mL) drink of water. The magnetic resonance imaging motility images were analysed using Spatio-Temporal Motility analysis STMM techniques. The area under the curve of the gastric motility contractions was calculated for each set and compared between techniques. The study visit was then repeated one week later. RESULTS: Data from 15 participants was analysed. There was a good correlation between the MRI antral motility plots area under the curve and corresponding perfused manometry motility area under the curve (r = 0.860) during both antral contractions and quiescence. CONCLUSION: Non-invasive dynamic magnetic resonance imaging of gastric antral motility coupled with recently developed, semi-automated magnetic resonance imaging data processing techniques correlated well with simultaneous, 'gold standard' water perfused manometry. This will be particularly helpful for research purposes related to oral absorption where the absorption of a drug is highly depending on the underlying gastrointestinal processes such as gastric emptying, gastrointestinal motility and availability of residual fluid volumes. CLINICAL TRIAL: This trial was registered at ClinicalTrials.gov as NCT03191045.

Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging.

BACKGROUND: Vagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the effects of different VNS parameters and polarity on postprandial gastric motility remain incompletely characterized. METHODS: In anesthetized rats (N = 3), we applied monophasic electrical stimuli to the left cervical vagus and recorded compound nerve action potential (CNAP) as a measure of nerve response. We evaluated to what extent afferent or efferent pathway could be selectively activated by monophasic VNS. In a different group of rats (N = 13), we fed each rat a gadolinium-labeled meal and scanned the rat stomach with oral contrast-enhanced magnetic resonance imaging (MRI) while the rat was anesthetized. We evaluated the antral and pyloric motility as a function of pulse amplitude (0.13, 0.25, 0.5, 1 mA), width (0.13, 0.25, 0.5 ms), frequency (5, 10 Hz), and polarity of VNS. KEY RESULTS: Monophasic VNS activated efferent and afferent pathways with about 67% and 82% selectivity, respectively. Primarily afferent VNS increased antral motility across a wide range of parameters. Primarily efferent VNS induced a significant decrease in antral motility as the stimulus intensity increased (R = -.93, P < .05 for 5 Hz, R = -.85, P < .05 for 10 Hz). The VNS with either polarity tended to promote pyloric motility to a greater extent given increasing stimulus intensity. CONCLUSIONS AND INFERENCES: Monophasic VNS biased toward the afferent pathway is potentially more effective for facilitating occlusive contractions than that biased toward the efferent pathway.

Using gastric emptying scintigraphy to evaluate antral contractions and duodenal bolus propagation.

Our aim was to investigate the feasibility of measuring antral contractions and duodenal bolus propagation (DBP) during dynamic antral contraction scintigraphy (DACS) as an assessment of antro-pyloro-duodenal coordination (APDC). Gastric emptying scintigraphy (GES) with DACS was performed with Tc-99m sulfur colloid (SC) using increasing doses of 74 MBq (2 mCi) for 10 subjects, 185 MBq (5 mCi) for 11, and 370 MBq (10 mCi) for 11. DACS was performed for 10 min after static images at 0, 30, 60, 120, 180, and 240 min in anterior and right anterior oblique (RAO) projections. Best projection and lowest dose of Tc-99m SC were assessed visually. DBP were quantified utilizing duodenal activity peaks from a region of interest in the first portion of the duodenum. DBP was better visualized in the RAO projection than anterior projection and using 185 MBq (5 mCi) and 370 MBq (10 mCi) compared with 74 MBq (2 mCi). DBP showed infrequent and irregular bolus transfers from the antrum to the duodenum. Antral activity peaks at 60 min averaged 2.91 ± 0.66 per minute and duodenum bolus peaks 0.36 ± 0.18 per minute (ratio 0.36/2.91 = 0.12). DBP activity peaks can be measured during GES with DACS but requires a 185-MBq (5 mCi) dose of Tc-99m SC radiolabeled test meal for adequate DBP signal detection and is better imaged in RAO than anterior projection. DBPs over the first 60 min postmeal ingestion are infrequent with only 12% of the antral contractions propagating into the duodenum. This methodology appears promising to assess APDC.NEW & NOTEWORTHY This study shows that duodenal bolus propagations after meal ingestion can be measured during gastric emptying scintigraphy using dynamic scintigraphy. Duodenal bolus propagation over the first 60 min postmeal ingestion are infrequent with only 12% of the antral contractions propagating into the duodenum. This methodology appears promising to assess antropyloroduodenal coordination in patients with unexplained symptoms of upper gastrointestinal dysmotility.

[Dynamic changes in early gastric cantrum motility in craniocerebral injury patients].

OBJECTIVE: To investigate the dynamic changes in early gastric antrum contraction in patients with craniocerebral injury. METHODS: The patients with craniocerebral injury admitted to neurosurgery intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from July to November in 2018 were enrolled. The changes in antral contraction frequency (ACF), antral contraction amplitude (ACA) and antral motility index (MI) were dynamically observed at 1-6 days after injury by ultrasonography. According to Glasgow coma score (GCS), the patients were divided into moderate to severe craniocerebral (GCS ≤ 11) and mild craniocerebral injury groups (GCS > 11). The differences in ACF, ACA and MI between the two groups were compared to observe the effect of craniocerebral injury on gastric antral motility. The patients were divided into simple supratentorial and supratentorial combined infratentorial lesion groups according to the lesion location of craniocerebral injury. The differences in ACF, ACA and MI between the two groups were compared to analyze the influence of lesion location on gastric antrum activity. RESULTS: A total of 68 patients with craniocerebral injury were screened during the study period, 50 patients were in accorded with the admission criteria, 17 patients were withdrawn from the observation because they could not tolerate the ultrasonography of gastric antrum or discharged from ICU. Finally, 33 patients were enrolled in the analysis. (1) The ACF, ACA and MI at 1 day after injury were lower [ACF (times/min): 1.67 (0.00, 2.00), ACA: 42.06 (0.00, 44.45)%, MI: 0.70 (0.00, 0.87)], and then gradually increased, till 6 days after injury, ACF was 1.83 (1.25, 2.79) times/min, ACA was 56.80 (33.25, 60.77)%, and MI was 0.89 (0.50, 1.70), which showed no differences among all time points (all P > 0.05). (2) The contractile function of gastric antrum in two groups of patients with different degrees of craniocerebral injury was decreased, especially ACA in patients with moderate to severe craniocerebral injury (n = 22), which showed significant differences at 3 days and 5 days after injury as compared with mild craniocerebral injury [n = 11; 3 days: 35.05 (0.00, 53.69)% vs. 58.51 (49.90, 65.45)%, 5 days: 39.88 (0.00, 77.01)% vs. 56.94 (41.71, 66.66)%, both P < 0.05], indicating that the degree of craniocerebral injury affected the contractive function of gastric antrum. However, there was no significant difference in ACF or MI between the two groups at different time points after injury. (3) The contractile function of gastric antrum was decreased after craniocerebral injury in both groups of patients with different lesion locations of craniocerebral injury. The ACF, ACA, and MI at 3-4 days in patients with supratentorial combined infratentorial lesion (n = 12) were slightly lower than those in patients with simple supratentorial lesion [n = 21; 3 days: ACF (times/min) was 0.83 (0.00, 2.00) vs. 2.25 (0.00, 3.00), ACA was 35.05 (0.00, 53.60)% vs. 49.93 (0.00, 63.44)%, MI was 0.29 (0.00, 1.07) vs. 1.23 (0.00, 1.61); 4 days: ACF (times/min) was 1.42 (0.50, 2.63) vs. 2.00 (1.63, 2.63), ACA was 30.45 (21.69, 60.61)% vs. 43.29 (38.41, 53.35)%, MI was 0.50 (0.15, 1.45) vs. 0.97 (0.66, 1.28)] without statistical differences (all P > 0.05), indicating that the lesion location might not affect the contractive function of gastric antrum. CONCLUSIONS: In the early stage of craniocerebral injury, the contractile function of gastric antrum was decreased, and the more severe the craniocerebral injury, the worse contractive function of gastric antrum.

Correlation between the motility of the proximal antrum and the high-frequency power of heart rate variability in freely moving rats.

BACKGROUND: Cardiac vagal tone can be monitored non-invasively via electrocardiogram measurements of the high-frequency power spectrum of heart rate variability (HF-HRV). Vagal inputs to the upper GI tract are cumbersome to measure non-invasively. Although cardiac and GI vagal outputs arise from distinct brainstem nuclei, the nucleus ambiguus, and the dorsal motor nucleus of the vagus, respectively, we aim to test the hypotheses that in freely moving rats HF-HRV power is correlated to proximal antral motility and can be altered by high levels of circulating estrogen and vagal-selective treatments known to affect antral motility. METHODS: Male and female Sprague-Dawley rats were implanted with a miniaturized strain gauge on the proximal gastric antrum and ECG electrodes to collect simultaneous antral motility and electrocardiogram. After recovery, male rats underwent baseline recordings before and after administration of saline (N = 8), cholecystokinin (CCK; N = 7), ghrelin (N = 6), or food (N = 6). Female rats (N = 6) underwent twice-daily recordings to determine baseline correlations during estrous cycle stages. KEY RESULTS: There was a significant positive correlation between HF-HRV and proximal antral motility at baseline in males and females with low, but not high, estrogen levels. In male rats, the significant positive correlation was maintained following CCK, but not ghrelin or food administration. CONCLUSIONS AND INFERENCES: Our data suggest that in rodents, HF-HRV positively correlates to proximal antral motility at baseline conditions in males and low-estrogen females or following interventions, such as CCK, known to affect vagal tone. This correlation is not observed when antral motility is influenced by more complex events.

Intraduodenal Administration of L-Valine Has No Effect on Antropyloroduodenal Pressures, Plasma Cholecystokinin Concentrations or Energy Intake in Healthy, Lean Men.

Whey protein is rich in the branched-chain amino acids, L-leucine, L-isoleucine and L-valine. Thus, branched-chain amino acids may, at least in part, mediate the effects of whey to reduce energy intake and/or blood glucose. Notably, 10 g of either L-leucine or L-isoleucine, administered intragastrically before a mixed-nutrient drink, lowered postprandial blood glucose, and intraduodenal infusion of L-leucine (at a rate of 0.45 kcal/min, total: 9.9 g) lowered fasting blood glucose and reduced energy intake from a subsequent meal. Whether L-valine affects energy intake, and the gastrointestinal functions involved in the regulation of energy intake, as well as blood glucose, in humans, is currently unknown. We investigated the effects of intraduodenally administered L-valine on antropyloroduodenal pressures, plasma cholecystokinin, blood glucose and energy intake. Twelve healthy lean men (age: 29 ± 2 years, BMI: 22.5 ± 0.7 kg/m²) were studied on 3 separate occasions in randomised, double-blind order. Antropyloroduodenal pressures, plasma cholecystokinin, blood glucose, appetite perceptions and gastrointestinal symptoms were measured during 90-min intraduodenal infusions of L-valine at 0.15 kcal/min (total: 3.3 g) or 0.45 kcal/min (total: 9.9 g), or 0.9% saline (control). Energy intake from a buffet-meal immediately after the infusions was quantified. L-valine did not affect antral, pyloric (mean number; control: 14 ± 5; L-Val-0.15: 21 ± 9; L-Val-0.45: 11 ± 4), or duodenal pressures, plasma cholecystokinin (mean concentration, pmol/L; control: 3.1 ± 0.3; L-Val-0.15: 3.2 ± 0.3; L-Val-0.45: 3.0 ± 0.3), blood glucose, appetite perceptions, symptoms or energy intake (kcal; control: 1040 ± 73; L-Val-0.15: 1040 ± 81; L-Val-0.45: 1056 ± 100), at either load (p > 0.05 for all). In conclusion, intraduodenal infusion of L-valine, at loads that are moderately (3.3 g) or substantially (9.9 g) above World Health Organization valine requirement recommendations, does not appear to have energy intake- or blood glucose-lowering effects.

Ultrasound assessment of gastric emptying time after a standardised light breakfast in healthy children: A prospective observational study.

OBJECTIVES: Current guidelines recommend 6 h of fasting for solids before anaesthesia. However, prolonged fasting may lead to discomfort, hunger, thirst, misbehaviour and lipolysis. To prevent this, a more liberal fasting regimen has been empirically implemented in our children's hospital, allowing a shorter fasting time of 4 h for a standardised light breakfast. AIM: The aim of this study was to determine the gastric emptying time after a standardised light breakfast in healthy children. DESIGN: A prospective observational noninterventional study. METHODS: After fasting overnight, the children had a standardised light breakfast. Before and afterwards, ultrasound examinations of the gastric antrum were performed hourly to determine the gastric antral area (GAA), which is a surrogate parameter for gastric volume in children in the right lateral position (RLP). Demographic data and fasting times are presented as mean ±â€ŠSD (range) and GAA as median (interquartile range). RESULTS: Twenty-two children aged 7.8 (2.5 to 13.6) years volunteered for this study. After fasting overnight [735 ±â€Š120 (467 to 930) min], the initial GAA was 3.06 (2.35 to 4.03) cm in RLP. After the light breakfast, GAA in RLP initially increased and decreased subsequently. After 4 h, GAA in RLP was lower than the initial value (median of differences -0.54, 95% confidence interval -1.00 to -0.07, P < 0.05). Correlation between GAA in RLP and fasting time was significant (r = -0.62, P < 0.0001). Using a linear regression model, the calculated mean gastric emptying time after the standardised light breakfast was 211 min for GAA = 3.06 cm. CONCLUSION: The study showed a mean gastric emptying time of less than 4 h after a standardised light breakfast in children. These results encourage our current clinical practice and support the efforts towards a more liberal fasting regimen for light meals in paediatric anaesthesia. TRIAL REGISTRATION: German Registry of Clinical Studies (DRKS-ID: DRKS 00013893).

Intragastric infusion of the bitter tastant quinine suppresses hormone release and antral motility during the fasting state in healthy female volunteers.

BACKGROUND: Intragastric administration of the bitter tastant denatonium benzoate inhibits the increase of motilin plasma levels and antral contractility. While these findings suggest that gastrointestinal bitter taste receptors could be new targets to modulate gastrointestinal motility and hormone release, they need confirmation with other bitter receptor agonists. The primary aim was to evaluate the effect of intragastric administration of the bitter tastant quinine-hydrochloride (QHCl) on motilin and ghrelin plasma levels. Secondly, we studied the effect on interdigestive motility. METHODS: Ten healthy female volunteers were recruited (33±4 y; 22±0.5 kg/m²). Placebo or QHCl (10 µmol/kg) was administered intragastrically through a nasogastric feeding tube after an overnight fast in a single-blind randomized fashion. Administration started 20 min after the first phase III of the migrating motor complex. The measurement continued for another 2 h after the administration. Blood samples were collected every 10 min with the baseline sample taken 10 min prior to administration. KEY RESULTS: The increase in plasma levels of motilin (administration; P=.04) and total ghrelin (administration; P=.02) was significantly lower after QHCl. The fluctuation of octanoylated ghrelin was reduced after QHCl (time by administration; P=.03). Duodenal motility did not differ. The fluctuation of antral activity differed over time between placebo and QHCl (time by administration; P=.03). CONCLUSIONS AND INFERENCES: QHCl suppresses the increase of both motilin and ghrelin plasma levels. Moreover, QHCl reduced the fluctuation of antral motility. These findings confirm the potential of bitter taste receptors as targets for modifying interdigestive motility in man.

Blind bedside postpyloric placement of spiral tube as rescue therapy in critically ill patients: a prospective, tricentric, observational study.

BACKGROUND: Various special techniques for blind bedside transpyloric tube placement have been introduced into clinical practice. However, transpyloric spiral tube placement facilitated by a blind bedside method has not yet been reported. The objective of this prospective study was to evaluate the safety and efficiency of blind bedside postpyloric placement of a spiral tube as a rescue therapy subsequent to failed spontaneous transpyloric migration in critically ill patients. METHODS: This prospective, tricentric, observational study was conducted in the intensive care units (ICUs) of three tertiary hospitals. A total of 127 consecutive patients with failed spontaneous transpyloric spiral tube migration despite using prokinetic agents and still required enteral nutrition for more than 3 days were included. The spiral tube was inserted postpylorically using the blind bedside technique. All patients received metoclopramide intravenously prior to tube insertion. The exact tube tip position was determined by radiography. The primary efficacy endpoint was the success rate of postpyloric spiral tube placement. Secondary efficacy endpoints were success rate of a spiral tube placed in the third portion of the duodenum (D3) or beyond, success rate of placement in the proximal jejunum, time to insertion, length of insertion, and number of attempts. Safety endpoints were metoclopramide-related and major adverse tube-associated events. RESULTS: In 81.9% of patients, the spiral feeding tubes were placed postpylorically; of these, 55.1% were placed in D3 or beyond and 33.9% were placed in the proximal jejunum, with a median time to insertion of 14 min and an average number of attempts of 1.4. The mean length of insertion was 95.6 cm. The adverse event incidence was 26.0%, and no serious adverse event was observed. CONCLUSIONS: Blind bedside postpyloric placement of a spiral tube, as a rescue therapy subsequent to failed spontaneous transpyloric migration in critically ill patients, is safe and effective. This technique may facilitate the early initiation of postpyloric feeding in the ICU. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OPN-16008206 . Registered on 1 April 2016.

Modified B-ultrasound method for measurement of antral section only to assess gastric function and guide enteral nutrition in critically ill patients.

AIM: To establish a modified B-ultrasound method of measuring the antral section only to assess gastric motility in healthy people, and evaluate its application in guiding enteral nutrition (EN) in critically ill patients. METHODS: First, 30 healthy volunteers were selected. The modified B-ultrasound method and the traditional B-ultrasound method were applied to assess gastric function. The correlation of indices of gastric function between the two groups was analyzed statistically. In addition, 64 critically ill patients were selected, and the modified B-ultrasound method and the gastric juice withdrawal method were applied to guide the implementation of EN. Daily caloric value, the time required to achieve complete EN, ICU stay, hospitalization time, and serum prealbumin and albumin levels were recorded and compared between the two groups. Kaplan-Meier survival curve was used to compare the complications of EN between the two groups. RESULTS: In healthy subjects, there was a good correlation among gastric emptying time, antral contraction frequency and antral motility index between the two groups (r = 0.57, 0.61 and 0.54, respectively). The study on critically ill patients also revealed that a better effect of EN was achieved in the modified B-ultrasound method group, in which patients had shorter ICU stay and hospitalization time and higher levels of serum prealbumin and albumin. The Kaplan-Meier survival analysis revealed that the improved B-ultrasound method was associated with significantly fewer EN complications (P = 0.031). CONCLUSION: The modified B-ultrasound method can provide a good real-time assessment of gastric function and has a better effect than the traditional method in guiding EN in critically ill patients.

Determination of a cut-off value of antral area measured in the supine position for the fast diagnosis of an empty stomach in the parturient: A prospective cohort study.

BACKGROUND: Ultrasound measurement of the antral cross-sectional area of the stomach, performed in the supine position, has been described for preoperative assessment of gastric content in the adult, but, to date, no study has determined the cut-off value of the antral area for the diagnosis of an empty stomach in the parturient. Nevertheless, previous studies in parturients have reported that the use of a simple qualitative grading scale (0 to 2) was reliable for the estimation of the gastric fluid volume. However, this qualitative grading score requires turning the parturient into the right lateral decubitus position for the ultrasound examination, something which may not be easily feasible, particularly in the case of an obstetric emergency. OBJECTIVE: To calculate the cut-off value of the antral area, measured in the supine position during established labour, for the diagnosis of 'empty' stomach. DESIGN: A prospective cohort study. SETTING: Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Lyon, France. PATIENTS: Seventy-three women in established labour. INTERVENTIONS: For each parturient, ultrasound assessment of gastric contents was performed in the supine and right lateral decubitus position and scored 0 to 3 on a qualitative grading scale. This assessment was followed by ultrasound measurement of the antral cross-sectional area in both the supine and right lateral positions. MAIN OUTCOME MEASURES: To assess the performance of the antral area measured in the supine position for the diagnosis of an 'empty' stomach (gastric antrum grade 0), a receiver operating characteristic curve was plotted, and the area under the receiver operating characteristic curve was calculated. RESULTS: Data from 73 women were analysed. For the diagnosis of grade 0, the cut-off value for the antral area measured in the supine position was 381 mm (sensitivity, 81%; specificity, 76% and negative predictive value, 80%). CONCLUSION: With a parturient lying in the supine position, a single assessment of the antral cross-sectional area may be used for the fast diagnosis of an empty stomach. This tool could be useful in assessing the risk of aspiration for parturients who require emergency anaesthesia during labour.

Prokinetic effects of a new 5-HT4 agonist, YKP10811, on gastric motility in dogs.

BACKGROUND AND AIM: Prokinetics have been considered the first-line medicine for treating delayed gastric emptying. The aim of this study was to explore the effects and mechanisms of a new 5-HT4 receptor agonist, YKP10811, on gastric motility in dogs. METHODS: Four experiments were performed in dogs: (i) dose-response effects of YKP10811 on liquid gastric emptying; (ii) effects and mechanisms of YKP10811 on solid gastric emptying delayed by glucagon; (iii) effects of low-dose YKP10811 on antral contractions; and (iv) effects of low-dose YKP10811 on gastric accommodation. RESULTS: No adverse events or cardiac dysrhythmia was noted. (i) High-dose YKP10811 (30 mg/kg) accelerated liquid gastric emptying from 15 to 90 min without inducing adverse events or cardiac dysrhythmia. YKP10811 at low doses (0.3, 1, and 3 mg/kg) accelerated gastric emptying in a dose-dependent manner. (ii) YKP10811 (0.1 mg/kg), but not tegaserod (0.3 mg/kg), significantly accelerated glucagon-induced delayed gastric emptying of solid, and the effect was completely blocked by GR113808. (iii) YKP10811 (0.3 mg/kg) enhanced antral contractions. (iv) YKP10811 did not alter gastric accommodation. CONCLUSIONS: YKP10811 seems to improve antral contractions and accelerate gastric emptying without altering gastric accommodation in dogs via the 5-HT4 mechanism and is substantially more potent than tegaserod. No adverse events were noted at a dose 300 times the lowest effective dose. YKP10811 may have a therapeutic potential for gastroparesis.

Contributions of upper gut hormones and motility to the energy intake-suppressant effects of intraduodenal nutrients in healthy, lean men - a pooled-data analysis.

We have previously identified pyloric pressures and plasma cholecystokinin (CCK) concentrations as independent determinants of energy intake following administration of intraduodenal lipid and intravenous CCK. We evaluated in healthy men whether these parameters also determine energy intake in response to intraduodenal protein, and whether, across the nutrients, any predominant gastrointestinal (GI) factors exist, or many factors make small contributions. Data from nine published studies, in which antropyloroduodenal pressures, GI hormones, and GI /appetite perceptions were measured during intraduodenal lipid or protein infusions, were pooled. In all studies energy intake was quantified immediately after the infusions. Specific variables for inclusion in a mixed-effects multivariable model for determination of independent predictors of energy intake were chosen following assessment for collinearity, and within-subject correlations between energy intake and these variables were determined using bivariate analyses adjusted for repeated measures. In models based on all studies, or lipid studies, there were significant effects for amplitude of antral pressure waves, premeal glucagon-like peptide-1 (GLP-1) and time-to-peak GLP-1 concentrations, GLP-1 AUC and bloating scores (P < 0.05), and trends for basal pyloric pressure (BPP), amplitude of duodenal pressure waves, peak CCK concentrations, and hunger and nausea scores (0.05 < P ≤ 0.094), to be independent determinants of subsequent energy intake. In the model including the protein studies, only BPP was identified as an independent determinant of energy intake (P < 0.05). No single parameter was identified across all models, and effects of the variables identified were relatively small. Taken together, while GI mechanisms contribute to the regulation of acute energy intake by lipid and protein, their contribution to the latter is much less. Moreover, the effects are likely to reflect small, cumulative contributions from a range of interrelated factors.

Functional physiology of the human terminal antrum defined by high-resolution electrical mapping and computational modeling.

High-resolution (HR) mapping has been used to study gastric slow-wave activation; however, the specific characteristics of antral electrophysiology remain poorly defined. This study applied HR mapping and computational modeling to define functional human antral physiology. HR mapping was performed in 10 subjects using flexible electrode arrays (128-192 electrodes; 16-24 cm2) arranged from the pylorus to mid-corpus. Anatomical registration was by photographs and anatomical landmarks. Slow-wave parameters were computed, and resultant data were incorporated into a computational fluid dynamics (CFD) model of gastric flow to calculate impact on gastric mixing. In all subjects, extracellular mapping demonstrated normal aboral slow-wave propagation and a region of increased amplitude and velocity in the prepyloric antrum. On average, the high-velocity region commenced 28 mm proximal to the pylorus, and activation ceased 6 mm from the pylorus. Within this region, velocity increased 0.2 mm/s per mm of tissue, from the mean 3.3 ± 0.1 mm/s to 7.5 ± 0.6 mm/s (P < 0.001), and extracellular amplitude increased from 1.5 ± 0.1 mV to 2.5 ± 0.1 mV (P < 0.001). CFD modeling using representative parameters quantified a marked increase in antral recirculation, resulting in an enhanced gastric mixing, due to the accelerating terminal antral contraction. The extent of gastric mixing increased almost linearly with the maximal velocity of the contraction. In conclusion, the human terminal antral contraction is controlled by a short region of rapid high-amplitude slow-wave activity. Distal antral wave acceleration plays a major role in antral flow and mixing, increasing particle strain and trituration.