Postprandial gastric antral contractions in patients with gastro-oesophageal reflux disease: a scintigraphic study

Abstract  Disturbed gastric contractility has been found in manometric studies in patients with gastro-oesophageal reflux disease (GORD), but the pathophysiological role of this abnormality is unclear. We aimed at assessing postprandial gastric antral contractions and its relationships with gastric emptying and gastro-oesophageal reflux in GORD patients. Fasted GORD patients ( n  = 13) and healthy volunteers ( n  = 13) ingested a liquid meal labelled with 72 MBq of ^99mTechnetium-phytate. Gastric images were acquired every 10 min for 2 h, for measuring gastric emptying half time. Dynamic antral scintigraphy (one frame per second), performed for 4 min at 30-min intervals, allowed estimation of both mean dominant frequency and amplitude of antral contractions. In GORD patients ( n  = 10), acidic reflux episodes occurring 2 h after the ingestion of the same test meal were determined by ambulatory 24-h oesophageal pH monitoring. Gastric emptying was similar in GORD patients and controls (median; range: 82 min; 58–126 vs 80 min; 44–122 min; P  = 0.38). Frequency of antral contractions was also similar in both groups (3.1 cpm; 2.8–3.6 vs 3.2 cpm; 2.4–3.8 cpm; P  = 0.15). In GORD patients, amplitude of antral contractions was significantly higher than in controls (32.7%; 17–44% vs 23.3%; 16–43%; P  = 0.01), and correlated positively with gastric emptying time ( R _s = 0.58; P  = 0.03) and inversely with the number of reflux episodes ( R _s = −0.68; P  = 0.02). Increased amplitude of postprandial gastric antral contractions in GORD may comprise a compensatory mechanism against delayed gastric emptying and a defensive factor against acidic gastro-oesophageal reflux.     

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

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

Motilin, erythromycin, and the gastric migrating motor complex: site of action

Motilin is a putative hormone which induces a premature migrating motor complex when administered exogenously, but the target organ for this hormonal effect is undetermined. Our aim was to determine whether motilin and the motilin agonist, erythromycin, induce a premature migrating motor complex via an effect directly on the stomach. Six dogs underwent splenectomy and ligation of all branches of the splenic artery except the left gastroepiploic and short gastric arteries to the proximal stomach. An intra-arterial catheter was placed in the proximal splenic artery for close intra-arterial injection of motilin and erythromycin directly to the gastric corpus/proximal antrum. After recovery, the minimum effective dose required to induce a premature migrating motor complex was determined for motilin and for erythromycin given close intra-arterially or intravenously (systemically) by monitoring upper gut myoelectric activity. Minimum effective doses of motilin and erythromycin were the same whether given intra-arterially or intravenously. The latency interval or the time to onset of a premature Phase III was less than 2 minutes for intra-arterial or intravenous administration (P > 0.05). The characteristics of induced-Phase HI activity (appearance, duration, velocity) did not differ from spontaneous Phase HI activity (P > 0.05). Although plasma motilin concentrations increased after threshold doses of both motilin and erythromycin, increases in plasma motilin occurred later after erythromycin (lOmin) than after exogenous motilin (3 min). Our findings suggest that motilin initiation of the migrating motor complex does not occur by independent stimulation of putative receptors in the gastric corpus or proximal antrum.     

Human postprandial gastric emptying of indigestible solids can occur unrelated to antral phase III

According to animal experiments, postprandial gastric emptying of indigestible solids is mainly related to the antral phase III activity of the migrating motor complex. Gastric emptying of indigestible solids in humans has not been directly correlated to pressure recordings. The aim of the present study was to investigate the postprandial emptying pattern of indigestible solids in humans and its relation to fed and fasted antral motility. Ten healthy volunteers participated. After an overnight fast they had a standard breakfast. Two sizes of radiopaque markers (ROMs) were given with the test meal; ten cubes each of side measurement 1.5 mm and 3 mm, respectively. Emptying of the ROMs from the stomach was followed by fluoroscopy with simultaneous antral manometry. In six of the subjects, fasting antral manometry was performed on one day and on another day, the emptying of 7 mm cylindrical particles together with 3 mm cubes, in the absence of a gastric tube was recorded. All ROMs were emptied within 5 h (range 1.5-4.5 h). In all subjects, the smaller particles (1.5 mm) showed a slight, insignificant tendency to move from the stomach more rapidly than the larger (3 mm) particles. None of the subjects had an antral phase III before all ROMs were emptied from the stomach. Instead, the typical irregular postprandial pressure activity was present in all subjects until the emptying was completed. Furthermore, the highest postprandial motility index during the emptying study was far below the motility index during phase III, but comparable to the motility index during late phase II. Emptying of the 7 mm particles occurred significantly more slowly at 1.5-2.5 h, but otherwise was similar to the emptying of the smaller particles. There was no difference between emptying of the 3 mm cubes with or without the presence of the tube. Contrary to common opinion, gastric emptying of indigestible solids after a meal can occur unrelated to the antral phase III, at least up to a particle size of 3 mm and perhaps even 7 mm. These findings are of great importance for the evaluation of gastric emptying of indigestible solids, including the pharmacodynamics of orally administered drugs.     

Effects of clonidine and sumatriptan on postprandial gastric volume response, antral contraction waves and emptying: an MRI study

Abstract Gastric emptying (GE) may be driven by tonic contraction of the stomach (‘pressure pump’) or antral contraction waves (ACW) (‘peristaltic pump’). The mechanism underlying GE was studied by contrasting the effects of clonidine (α₂‐adrenergic agonist) and sumatriptan (5‐HT₁ agonist) on gastric function. Magnetic resonance imaging provided non‐invasive assessment of gastric volume responses, ACW and GE in nine healthy volunteers. Investigations were performed in the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal) under placebo [0.9% NaCl intravenous (IV) and subcutaneous (SC)], clonidine [0.01 mg min^?1 IV, max 0.1 mg (placebo SC)] or sumatriptan [6 mg SC (placebo IV)]. Total gastric volume (TGV) and gastric content volume (GCV) were assessed every 5 min for 90 min, interspersed with dynamic scan sequences to measure ACW activity. During gastric filling, TGV increased with GCV indicating that meal volume dictates initial relaxation. Gastric contents volume continued to increase over the early postprandial period due to gastric secretion surpassing initial gastric emptying. Clonidine diminished this early increase in GCV, reduced gastric relaxation, decreased ACW frequency compared with placebo. Gastric emptying (GE) rate increased. Sumatriptan had no effect on initial GCV, but prolonged gastric relaxation and disrupted ACW activity. Gastric emptying was delayed. There was a negative correlation between gastric relaxation and GE rate (r² = 49%, P < 0.001), whereas the association between ACW frequency and GE rate was inconsistent and weak (r² = 15%, P = 0.05). These findings support the hypothesis that nutrient liquid emptying is primarily driven by the ‘pressure pump’ mechanism.     

Analysis of motor patterns in the isolated guinea-pig large intestine by spatio-temporal maps

We investigated and quantified the spontaneous patterns of motility in the isolated guinea-pig proximal and distal colon taken from adult animals. During spontaneous emptying, profiles of proximal and distal colon were recorded with a video camera, and image analysis was used to construct spatio-temporal maps of the motions of the intestinal wall. Four patterns of motility were recorded. In the proximal colon there were neurally mediated contractions that propagated in the aboral direction at 4.1 mm s(-1), gently pushing the soft contents aborally; these are likely to represent spontaneous peristaltic behaviour. A second pattern, insensitive to tetrodotoxin (TTX; 0.6 microM), consisted, in both oral and aboral propagation, of shallow contractions of the circular muscle (ripples). These contractions propagated aborally at 2.8 +/- 0.45 mm s(-1) and orally at 2.03 +/- 0.31 mm s(-1) (n=10). Of these TTX-resistant contractions, 22.5% propagated both orally and aborally from a common origin. The orally propagated component of these myogenic contractions is likely to correspond to the antiperistalsis widely described in the proximal colon. In the distal colon, two patterns of motor activity were observed. One, induced by natural or artificial pellets, consisted of peristaltic contractions that pushed the pellets aborally at 0.8 mm s(-1) and expelled a pellet every 108 s. In the interval between pellet propulsion and after the distal colon had emptied all of its pellets a second, nerve-mediated pattern of motor activity, consisting of clusters of annular circular muscle contractions separated by short dilated regions, slowly propagated aborally at 0.3 mm s(-1). Both of these motor patterns were abolished by TTX (0.6 microM). A latex balloon, inserted at the oral end of the empty isolated distal colon and inflated to a size similar to faecal pellets, was propelled at 1.4 mm s(-1). Epoxy resin-covered natural pellets were propelled at a similar speed of 1.6 mm s(-1).Our data revealed that myogenic and neurogenic patterns of propagated contractions in the colon occur in isolated preparations and are involved in emptying the colon.     

Propagation of giant migrating contractions between the small intestine,cecum and colon during radiation

Background Radiation increases the frequency of small intestinal and colonic giant migrating contractions (GMCs). These contractions contribute to the diarrhea and cramping after radiation therapy and are coordinated with one another across the ileocolonic (IC) junction. Methods We investigated the coordination of contractile activity between the small intestine, cecum and colon in five canines following circumferential myotomy on the ileum at the IC junction and compared it to intact animals. Studies were performed before and during a radiation schedule. Key Results Myotomy increased the frequency of small intestinal GMCs prior to irradiation. In intact animals, the duration and amplitude of cecal GMCs decreased when multiple contractions occurred in rapid succession. This is in contrast to small intestinal and colonic GMCs and suggests a different mechanism of propagation for GMCs within the cecum. Ileal myotomy dramatically decreased the frequency of propagating radiation‐induced colonic GMCs. The total number of colonic GMCs was not altered. Colonic contractile activity was disrupted in intact animals during irradiation. However, after ileal myotomy, irradiation did not affect the pattern of colonic contractile states. Diarrhea in irradiated animals with myotomy started earlier than intact animals. This may be related to the frequency of small intestinal GMCs. Conclusions & Inferences Our findings suggest importance of the enteric neural connections at the IC region to contractile disorders of both the small and large intestine. The anatomic relationship between the canine IC junction is similar to the human ileo‐appendiceal‐colonic region and surgical manipulations of this area may likewise affect human contractile activity.     

Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy

Abstract  Gastric emptying of digestible solids occurs after trituration of food particles. Non-digestible solids are thought to empty with phase III of the migrating motor complex (MMC). The aim of this study was to determine if a non-digestible capsule given with a meal empties from the stomach with return of the fasting phase III MMC or during the fed pattern with the solid meal. Fifteen normal subjects underwent antroduodenal manometry and ingestion of a radiolabelled meal and SmartPill wireless pH and pressure capsule. In five subjects, emptying of the SmartPill was studied in the fasting period by ingesting the SmartPill with radiolabelled water. The SmartPill emptied from the stomach within 6 h in 14 of 15 subjects. SmartPill pressure recordings showed high amplitude phasic contractions prior to emptying. SmartPill gastric residence time (261 ± 22 min) correlated strongly with time to the first phase III MMC (239 ± 23 min; r  = 0.813; P  < 0.01) and correlated moderately with solid-phase gastric emptying ( r  = 0.606 with T-50% and r  = 0.565 with T-90%). Nine of 14 subjects emptied the capsule with a phase III MMC. In five subjects, the SmartPill emptied with isolated distal antral contractions. In five subjects ingesting only water, SmartPill gastric residence time (92 ± 44 min) correlated with the time to the first phase III MMC (87 ± 30 min; r  = 0.979; P  < 0.01). The non-digestible SmartPill given with a meal primarily empties from the stomach with the return of phase III MMCs occurring after emptying the solid-phase meal. However, in some subjects, the SmartPill emptied with isolated antral contractions, an unappreciated mechanism for emptying of a non-digestible solid.     

The migrating motor complex modulates intestinal motility response and rate of gastric emptying of caloric meals

Abstract The present study elucidates whether the phase of the migrating motor complex (MMC) present at the moment of food intake modulates postprandial motor response and rate of gastric emptying of caloric meals. Eight healthy male volunteers with a mean age of 26 years were examined twice. During water-perfused gastroduodenal manometry, a liquid meal with paracetamol added as a marker was orally administered during phase I and late phase II. Paracetamol appeared in serum 14.1 ± 3.8 min and 9.1 ± 4.0 (mean ± SD) min, respectively, after intake of the meal (P < 0.02). The area under the curve of s-paracetamol until 25 min after intake was 232 ± 169 μmoll_-1 min and 362 ± 130 (P < 0.05), respectively. When taken during late phase II, a phase III-like activity occurred within 2.1 ± 1.3 min in the duodenum, and was succeeded by quiescence. During phase I, the meal invariably initiated irregular contractions within 4 min. The phase of MMC during which a caloric meal is ingested modulates duodenal motor response and rate of gastric emptying during the initial postprandial period. Initial postprandial motor activity thus represents the combined effect of nutrient stimulation and the underlying enteric biorhythm as reflected by phase of MMC.     

The nocturnal jejunal migrating motor complex: defining normal ranges by study of 51 healthy adult volunteers and meta-analysis

Interdigestive human small bowel motility is characterized by the migrating motor complex (MMC). The aims of this study were to: (i) establish the normal range of variables of the nocturnal jejunal MMC and (ii) incorporate these data in a subsequent meta-analysis. Eighty-one recordings were performed by prolonged (24 h) ambulatory manometry in 51 subjects in two centres. Quantitative analysis was undertaken of 419 Phase III and 332 Phase II episodes. Adjusted mean values of seven variables were calculated using a mixed-effects model. Meta-analysis of pooled published data to generate a reliable 95% reference range was also performed. Adjusted mean values and confidence intervals are presented for all seven variables. Intrasubject variances were large in comparison with intersubject. Meta-analysis of 19 studies (356 pooled patients) meeting inclusion criteria produced wide reference ranges. At least five such ranges are useful for the detection of abnormality in the individual. This is the largest study of normal volunteers presented to date, with ranges for many variables produced using appropriate statistical methodology. A model for definition of abnormality has been proposed. We recommend that these data may be used by investigators in this field as a complement to other existing indicators of small bowel dysmotility.     

Phase III of the migrating motor complex: associated with endogenous xenin plasma peaks and induced by exogenous xenin

Xenin, a recently discovered peptide produced by specific endocrine cells of the duodenal mucosa, has shown exocrine, endocrine and motility effects in the gastroenteropancreatic system in animal experiments. The aim of the present investigation was to study the role of xenin in the regulation of duodenojejunal motility of humans. Twenty-nine healthy volunteers from the hospital staff gave informed consent to participate in this investigation. In 20 volunteers, we determined plasma concentrations of immunoreactive xenin at 15 min intervals over a mean time period of 8 h fasting and recorded the interdigestive motor activity of the duodenojejunum. In a double-blind randomized crossover study on other nine subjects, synthetic xenin in a dose of 4 pmol kg-1 min-1 or placebo was infused for 10 min intravenously in the interdigestive period and postprandially after a liquid meal. Duodenojejunal motility was recorded simultaneously. Predefined interdigestive xenin plasma peaks were found to be significantly associated with the phases III of the migrating motor complex. In the interdigestive period, xenin induced a premature phase III activity in each volunteer; this was followed by a second phase III in five out of nine subjects. In the postprandial state, xenin significantly increased contraction frequency and the percentage of aborally propagated contractions. These findings suggest a role of the peptide hormone xenin in modulating interdigestive and postprandial duodenojejunal motility in humans.