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PubMed2003

Computational model of the migrating motor complex of the small intestine.

The migrating motor complex (MMC) is a cyclic motor pattern with several phases enacted over the entire length of the small intestine. This motor pattern is initiated and coordinated by the enteric nervous system and modulated by extrinsic factors. Because in vitro preparations of the MMC do not exist, it has not been possible to determine the intrinsic nerve circuits that manage this motor pattern. We have used computer simulation to explore the possibility that the controlling circuit is the network of AH/Dogiel type II (AH) neurons. The basis of the model is that recurrent connections between AH neurons cause local circuits to enter a high-firing-rate state that provides the maximal motor drive observed in phase III of the MMC. This also drives adjacent segments of the network causing slow migration. Delayed negative feedback within the circuit, provided by activity-dependent synaptic depression, forces the network to return to rest after passage of phase III. The anal direction of propagation is a result of slight anal bias observed in projections of AH neurons. The model relates properties of neurons to properties of the MMC cycle: phase III migration speed is governed by neuron excitability, MMC cycle length is governed by the rate of recovery of synaptic efficacy, and phase III duration is governed by duration of slow excitatory postsynaptic potentials in AH neurons. In addition, the model makes experimental predictions that can be tested using standard techniques.

Algorithms↗

PubMed1999

Gastrointestinal sounds and migrating motor complex in fasted humans.

OBJECTIVE: We investigated the relationships among gastrointestinal sounds, gastrointestinal manometric findings, and small intestinal transit time in healthy fasted humans. METHODS: Gastrointestinal sounds acquired with two microphones attached to the upper and lower abdominal walls of healthy subjects were quantified with a computer-aided sound analysis program. Antroduodenal contractions were recorded by manometry. Small intestinal transit time was measured by breath hydrogen testing after intraduodenal administration of lactulose. RESULTS: The sum of the gastrointestinal sound amplitudes (sound index) in both the upper and lower abdomen changed with time, coinciding with the gastric phases of the migrating motor complex. The sound indices in the upper and lower abdomen were 59.0+/-24.8 and 98.1+/-21.6 mV/min in phase 1, 95.5+/-27.9 and 127.4+/-34.9 mV/min in phase 2, and 132.8+/-12.4 and 188.5+/-73.4 mV/min in phase 3, respectively. There were no significant differences among motility phases in terms of the mean duration or frequency of each sound event. Intravenous erythromycin induced phase 3 in the stomach and doubled the sound index. Somatostatin analogue induced phase-3-like clustered contractions in the duodenum, but inhibited antral contractions and decreased the sound index. The small intestinal transit time was shorter and the sound index increased after intravenous metoclopramide, compared with controls. Scopolamine delayed small intestinal transit time and decreased the sound index. CONCLUSIONS: This study is the first to document the relationships between gastrointestinal sounds and the migrating motor complex. The chronological relation between antral motility and gastrointestinal sounds, and the dissimilar effects of erythromycin and somatostatin, suggest that antral contractions increase gastrointestinal sounds, perhaps by supplying gas into the intestine.

Adult↗

PubMed1996

Dysfunction in gastric myoelectric and motor activity in Helicobacter pylori positive gastritis patients with non-ulcer dyspesia.

Helicobacter pylori (Hp) infection has been shown to affect gastric acid secretion and the somatostatin-gastrin ratio but its effects on gastric motility have not been evaluated. This study was carried out in 12 patients (10 males and 2 females, mean age 33 +/- 6 yrs) who underwent endoscopy and Campylobacter-like Organism (CLO)-test. All patients were found initially to be Hp positive according to CLO-test. Gastric emptying was evaluated by measuring antral diameter with ultrasonography (Hitachi EUB 240) in fasted and fed patients. Electrogastrography (EGG) with antral manometry were done 5 h before and 4 h after a meal before the therapy and one month after the eradication with triple therapy (lanzoprazole 30 mg daily- 2 x 250 mg clarithromycin 500 mg t.i.d.-3 x 500 mg and metronidazole 500 mg b.i.d.-2 x 500 mg). In Hp positive patients before the triple therapy the mean fasted antral diameter was 4.3 cm2, initial EGG showed significant dysrhythmia of electrical control activity (ECA) with tachygastria up to 25% of recording time in 9 of 12 Hp positive patients without normal increase of the power of signal in any of tested subjects. In 7 Hp positive fasted antral manometry failed to exhibit gastric phases III of the migrating motor complex (MMC). Hp eradication was accomplished in 10 of 12 examined patients and this was followed by a decrease in tachygastria to 3 cpm rhythm with an increase of the ECA power after meal. Phase III of MMC was observed again in 7 Hp negative patients with a decrease of fasted antral diameter (p < 0.05). Fasted and fed antral motility pattern increased after eradication. Two patients remained Hp positive after standard therapy. We conclude that most symptomatic non ulcer dyspeptic Hp positive patients show changes in ECA and antral hypomotility that are associated with Hp infections.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1994

Motilin receptor: a model for development of prokinetics.

Erythromycin and related macrolides act as smooth muscle and neural receptors to contract rabbit duodenum and induce phase III migrating motor complex (MMC) activity in intact dogs. A recently developed motilin antagonist confirms that motility effects of erythromycin are mediated by motilin receptors. Despite species, organ, and tissue heterogeneity of motilin receptors, binding experiments with rodent antral smooth muscle tissue provide a good model for the development of this new class of prokinetics.

Animals↗

PubMed1999

The effects of omeprazole on intragastric pH, intestinal motility, and gastric emptying rate.

BACKGROUND: The present study was designed to investigate whether omeprazole changes the characteristics and thereby the functions ascribed to fasting intestinal motility, postprandial motility, postprandial pH, and gastric emptying. METHODS: Ten healthy subjects were investigated. The studies were performed after 10 days of treatment with 40 mg omeprazole daily/placebo. Duodenal pressures and intragastric pH were detected by strain-gauge transducers and a pH electrode attached to a miniature computer. The meal consisted of an omelette labelled with 99mTc-sulphur colloids followed by 150 ml water labelled with 111In-diethylenetriamine pentaacetic acid. RESULTS: The difference in fasting intragastric pH between the two series was highly significant. The profile from the placebo series showed a relationship between phase activity and pH. The pH increased from phase I (median, 1.3; 95% confidence interval (CI), 0.9-1.6) to a maximum at 25% (1.8 (0.9-2.1)) and 50% (1.6 (1.1-3.8)) of cycle duration and decreased thereafter until the end of the cycle. The profile from the omeprazole series showed significantly higher values during the entire cycle but no relationship between phase activity and pH. Pretreatment with omeprazole was followed by a delay in gastric emptying of liquid at 30 min (64% (49%-66%) (omeprazole series) versus 78% (67%-83%); P < 0.01) and solid at 180 min (71% (48%-86%) (omeprazole series) versus 96% (87%-100%); P < 0.01). There was no significant difference in duration of postprandial motility (305 min (157-350 min) (omeprazole) versus 259 min (129-403 min)). CONCLUSIONS: Omeprazole eliminates the temporal relationship between intragastric pH and characteristics of the migrating motor complex and induces a delay in gastric emptying of both liquid and solid. A non-significant increase in duration of postprandial motility may represent a type-II error.

Adult↗

PubMedDate not supplied

Changes in interdigestive migrating electric complex induced by motion sickness.

This study aimed to investigate, by means of an intralumenal recording technique, the influence of motion sickness on the interdigestive migrating electric complex (IDMEC) of the gastrointestinal system of susceptible subjects. The results indicate that vestibular stimulations significantly change the duration of IDMEC phases (p < 0.05 and p < 0.01): phase I in both the stomach and duodenum decreases, the duration of phase II and phase III is changed differently in the stomach and in the duodenum.

Adult↗

PubMed1992

Effect of meal composition and sham feeding on duodenojejunal motility in humans.

The disruptive effect of meals of different fat content and caloric value and of sham feeding on the interdigestive migrating motor complex (IDMMC) was studied in eight healthy subjects using an ambulatory recording system that allowed continuous monitoring of small bowel motility for three consecutive days. The durations of fed pattern were not significantly different between meals of 800 kcal/50% fat, 400 kcal/50% fat, and 800 kcal/25% fat, but were significantly longer compared to IDMMC cycle length and sham feeding. The latter two were not significantly different. On a separate day, five subjects consumed a meal of 400 kcal/9% fat and a second one of 800 kcal/50% fat. The duration of the fed pattern following the high fat meal was significantly longer than the low fat one. Sham feeding significantly increased plasma concentrations of gastrin and neurotensin (NT), but did not affect those of cholecystokinin (CCK), insulin, and peptide YY (PYY). The various variables of the IDMMC were not different during the two nights of the study, and velocity of migration of phase III during the first day and both nights was similar. We conclude that the duration of the fed pattern depends, in part, on the composition of the meal. Sham feeding, resulting in an increase in both plasma gastrin and NT concentrations, does not disrupt the IDMMC. When using thin probes, IDMMC is stable during prolonged recording.

Adult↗

PubMed1999

Evidence that nitric oxide mechanisms regulate small intestinal motility in humans.

BACKGROUND: Non-cholinergic non-adrenergic neural mechanisms involving nerves containing NO have been shown to modulate smooth muscle in the gastrointestinal tract, and it has been suggested that release from tonic NO inhibition may be important in the regulation of cyclical fasting small intestinal motility. AIMS: To evaluate the role of NO mechanisms in the regulation of fasting small intestinal motor activity in humans using a specific NO synthase inhibitor, NG-monomethyl-L-arginine ( L-NMMA). METHODS: In seven healthy male volunteers, duodenal and jejunal pressures were measured for four hours with a nine lumen manometric catheter. Volunteers attended on four separate days on which they received an intravenous infusion either saline or L-NMMA (0.5, 2, or 4 mg/kg/h) in random order. Intravenous infusions began 10 minutes after completion of phase III of the migrating motor complex (MMC). RESULTS: The first episode of phase III activity occurred earlier after infusion of 2 and 4 mg/kg/h L-NMMA than after infusion of 0.5 mg/kg/h L-NMMA or saline (mean (95% confidence interval) 52 (36-68) and 57 (18-97) v 116 (69-193) and 145 (64-226) minutes respectively) with a resultant MMC cycle length of 82 (59-105) and 86 (46-126) v 132 (49-198) and 169 (98-240) minutes respectively. The total number of phase III activities during the four hour recording was increased (p<0.05) by L-NMMA at a dose of 4 mg/kg/h (2 (1-3)) but not at 2 mg/kg/h (1.5 (1-2)) or 0.5 mg/kg/h (1.3 (1-2)) compared with saline (1.3 (0.6-2)). L-NMMA had no effect on the duration, velocity, number of contractions per minute, length of migration, or site of origin of phase III of the MMC. The duration of phase I activity was shorter (p<0.05) with 4 mg/kg/h L-NMMA than with saline (12 (1-23) v 31 (19-44) minutes). CONCLUSIONS: These observations suggest that NO mechanisms play a role in the regulation of fasting small intestinal motor activity in humans.

Adult↗

PubMed2000

Acute intraduodenal bile salt depletion leads to strong gallbladder contraction, altered antroduodenal motility and high plasma motilin levels in humans.

Cholecystokinin is the main hormone involved in postprandial gallbladder contraction. There is also considerable gallbladder contraction in the fasting state, associated with phase III of the gastrointestinal migrating motor complex and release of the hormone motilin. It has been proposed that intraduodenal bile salts exert a negative-feedback control on postprandial cholecystokinin release and resulting gallbladder contraction. We wanted to elucidate whether a similar control mechanism on gallbladder contraction exists in the fasting state. We therefore performed gallbladder ultrasonography and 24-h antroduodenal motility registrations and determined plasma cholecystokinin and motilin levels in six healthy subjects before and after acute (4 g) and chronic (8 days; 8 g day(-1)) oral cholestyramine. Acute cholestyramine strongly decreased gallbladder volumes and increased motilin without changed cholecystokinin levels. There was a negative relationship between gallbladder volumes and plasma motilin levels. Although there was a persistent fasting pattern of antroduodenal motility, its cycle length was increased (P < 0.03) with markedly longer phase II (P < 0. 005). Fasting gallbladder volumes 24 h later were still strongly decreased but gradually increased to pretreatment levels. Before and after 8 days cholestyramine, interdigestive and postprandial gallbladder emptying, intestinal migrating motor complex and hormone levels did not differ. We conclude that acute (but not chronic) intraduodenal bile salt depletion with cholestyramine affects gallbladder and antroduodenal motility, possibly partly related to motilin release.

Adult↗

PubMed2004

[Effect of dachengqi granule on human gastrointestinal motility].

OBJECTIVE: To study the therapeutic effect and mechanism of Dachengqi granule (DCQG) on some digestive motility disturbed diseases. METHODS: Gastroduodenojejunal manometry, electrogastrography (EGG), RIA of motilin and orocecal transit time test were applied to directly observe the effect of DCQG on human gastrointestinal motility. RESULTS: DCQG could significantly improve the postoperational EGG disorder, elevate the amplitude and time of migrating motor complex (MMC) phase III, prevent gastrointestinal reversed peristalsis, increase the blood level of motilin, decrease the orocecal transit time, and promote the recovery of gastrointestinal motility. CONCLUSION: DCQG is an effective digestive kinetic agent, which could be medicated conveniently in treating digestive motility disturbed diseases.

Adult↗

PubMed1996

[Changes in intestinal motility after massive small bowel resection with a reversed jejunal segment].

To evaluate the functioning and effectiveness of a 20-cm reversed jejunal segment after 75-80% massive small bowel resection (MSBR), and whether migrating polarity changes or not, we continuously measured the postoperative bowel motility (using bipolar electrodes and/or contractile strain gage force transducers) in interdigestive and postprandial conscious dogs in short- (2-5 weeks) and long-term (6-10 months) after surgery. The fasting migrating myoelectric (or motor) complex (MMC) arising from the duodenum was often interrupted at the jejunum above the proximal anastomosis and did not migrate smoothly to the reversed segment or terminal ileum. In addition, brief small discordant contractions were frequent in the jejunum above the proximal anastomosis and the proximal part of the reversed segment. The duodenal MMCs predominantly propagated to the ileum through the inherent anatomic continuity of the bowel. These findings of the MMC propagation pattern are very similar in short- and in long-term after surgery. The duration of the postprandial period without duodenal MMC activity was markedly longer in short-term, but shorter in long-term (both were significantly longer than in controls). Marked dilatation of the jejunum and reversed jejunal segment was noted across the proximal anastomosis. These results suggest that the transit time and passage of intestinal contents can be delayed and stagnated for at least 10 months after MSBR with a 20-cm reversed jejunal segment. Although, reports on the polarity of peristalsis in the reversed segment in long-term followup have been contradictory in both experimental and clinical studies, this results support the conclusion that the reversed jejunal segment maintains its inherent propagative polarity and pattern over a long postoperative period.

Anastomosis, Surgical↗

PubMed2001

Jejunal manometry predicts tube feeding intolerance in the postoperative period.

Postoperative nutrition is best provided enterally; however, patients often develop intolerance to enteral feedings. Our aim was to prospectively identify abdominal examination and jejunal pressure activity associated with postoperative intolerance of enteral feedings. Twenty-nine patients underwent abdominal operation and needle catheter jejunostomy placement. Elemental tube feedings were started on the day after surgery and advanced to the caloric goal rate over three days. Patients whose feedings were slowed at the attending surgeon's discretion were defined as intolerant. Jejunal manometry and a standardized abdominal exam were performed on postoperative days 1, 3, and 5. Fifteen patients (52%) were intolerant of tube feedings and had decreased jejunal motor activity but more active bowel sounds prior to feedings. After feedings, intolerant patients developed abdominal distension, but other abdominal findings were inconsistent. A marked decrease in phase II of the migrating motility complex (MMC) and the lack of a fed response were present in both groups. The overall jejunal motility present on day 1 following surgery identifies patients that will not tolerate enteral feedings. The abdominal examination, MMC parameters, and motor response to feeding did not predict feeding intolerance.

Colectomy↗

PubMedDate not supplied

Agonist effect of erythromycin and its analogues on motilin receptors. A new family of prokinetics? Clinical interest.

It has been known since long that erythromycin may cause unpleasant gastro-intestinal side-effects such as nausea and vomiting. Recent studies however show that at low doses erythromycin may have a beneficial effect. Erythromycin induces the migrating motor complex in the fasted state and after a meal it accelerates gastric emptying. Although largely preliminary, its effects on esophageal, small intestinal, colonic and biliary tract motility have now been studied in several pathological conditions. Erythromycin is certainly a powerful gastrokinetic. Its antibiotic properties are a disadvantage, but more powerful derivatives devoid of antibacterial properties may soon become available. They form a new family of prokinetics.

Erythromycin↗

PubMed1997

Orthotopic liver transplantation improves small bowel motility disorders in cirrhotic patients.

Altered small intestinal motility has been observed in patients with liver cirrhosis. Its pathophysiology remains to be defined. Our aim was to investigate the effect of orthotopic liver transplantation on small intestinal dysmotility in patients with liver disease. Two patients were studied both before and after orthotopic liver transplantation. Abnormal migrating motor complex activity and prominent clustered contractions present preoperatively normalized within 6 months after the surgical procedure. This finding might represent an additional benefit of liver transplantation considering that altered motility may be involved in bacterial overgrowth and infections observed in these patients.

Adult↗

PubMed1996

Extrinsic nervous control of retrograde giant contraction during vomiting in conscious dogs.

Neural mechanisms controlling retrograde giant contraction during vomiting were studied in six conscious dogs with implanted strain gauge force transducers. The small intestine was divided into proximal (P), middle (M), and distal (D) segments. These segments were transplanted on intact mesenteric neurovascular pedicles. In three dogs, M and D segments were interchanged (group A). In three dogs, P and M segments were interchanged (group B). Before transplantation, apomorphine-induced vomiting caused retrograde giant contractions, starting from the M segment and rapidly migrating to the stomach. However, in group A, even after recovery of interdigestive migrating contractions migration, retrograde giant contractions during vomiting always originated in the distally interchanged M segment and jumped to the P segment without migration to the D segment. In group B, the retrograde giant contraction always originated in the proximally interchanged M segment and successively occurred in the distally interchanged P segment. We conclude that origination and migration of retrograde giant contractions are extrinsically controlled. These motor events during vomiting are thought to be a specific motor function that does not exist in the lower small intestine, and retrograde giant contraction during vomiting may originate in the mid-small intestine.

Animals↗

PubMed2000

A normal gastrointestinal motility excludes chronic intestinal pseudoobstruction in children.

Gastrointestinal manometry has gained wide acceptance in the approach to patients with suspected enteric neuromuscular disorders. However, performing gastrointestinal manometry in these subjects without a previous exhaustive diagnostic evaluation is unjustified. Twelve children (median age: 7.0 years; range: 8 months-13 years), with clinical and x-ray features suggesting chronic intestinal pseudoobstruction, were referred to our unit for gastrointestinal manometry. The latter was performed with a perfused catheter for 5 hr in the fasting state and for 90 min after feeding. Data were compared with those recorded in eight age-matched controls. In all patients and controls, interdigestive motor complexes with propagated phases III were detected; a regular postprandial antroduodenal motor activity was also recorded. Patients and controls did not differ for fed antral and duodenal motility indexes, fed antroduodenal coordination, and length of duodenal phase III. Most of the patients showed short or prolonged bursts of nonpropagated activity in the fasting and/or fed states; in four cases fasting and/or fed sustained phasic activity was recorded. Manometric evidence of migrating motor complexes and postfeeding activity did not support the diagnosis of intestinal pseudoobstruction and suggested redirecting the diagnostic evaluation. Final diagnoses were: Munchausen syndrome-by-proxy (four cases), celiac disease (two cases), intestinal malrotation (two cases), Crohn's disease (two cases), multiple food intolerance (one case), and congenital chloride-losing diarrhea (one case). It is concluded that in children with suspected chronic intestinal pseudoobstruction manometric evidence of migrating motor complexes and fed motor activity excludes an enteric neuromuscular disorder and suggests a reassessment of the diagnostic work-up. Furthermore, if gastrointestinal manometry shows migrating motor complexes and postfeeding motor activity, qualitative abnormalities of the manometric tracings do not indicate an underlying enteric neuromuscular disorder and must not be overemphasized. Patients referred for gastrointestinal manometry should previously undergo an extensive diagnostic investigation to exclude disorders mimicking chronic intestinal pseudoobstruction.

Adolescent↗

PubMed2002

Ileal manometry in children following ileostomies and pull-through operations.

Our aim was to analyse the patterns of ileal contractions in children. We reviewed the charts of 23 children who had ileal manometry studies (16 males), mean age 7 years (range 2 months to 17 years). We positioned the manometry catheters with 4-8 recording sites, 5 or 15 cm apart, through ileostomies fashioned for clinically indicated reasons. We studied six additional children with persistent faecal soiling following endorectal pull through for Hirschsprung's disease; the catheters were positioned through the anus and colon into the ileum. We recorded phasic and tonic intermittent contractions in all the subjects, clustered contractions (rate 5-9 min-1, duration 20-120 s) in 19 subjects with ileostomies and four with endorectal pull throughs. In 13 children there were prolonged propagated contractions, > 60 mmHg in amplitude, > 15 s in duration, propagating at rates of 2-6 cm s-1 over at least 20 cm. The migrating motor complex was rare; in 55 h of fasting recording there were two phase III sequences. There are four distinctive features of ileal manometry recordings in children: random intermittent contractions, clustered contractions, prolonged propagated contractions and tonic contractions. The features of ileal motility differ from motility in the proximal small bowel.

Adolescent↗

PubMed1998

Actions of the 5-hydroxytryptamine 1 receptor agonist sumatriptan on interdigestive gastrointestinal motility in man.

BACKGROUND: Pharmacological studies of the enteric nervous system have shown the presence of several subtypes of 5-hydroxytryptamine (5HT) receptor, which might be involved in control of the migrating motor complex. AIMS: To study the effect of sumatriptan, an agonist of enteric neuronal 5HT1p receptors, on interdigestive motility in man. SUBJECTS AND METHODS: In 12 healthy subjects, interdigestive motility was recorded manometrically in the upper gastrointestinal tract. In seven subjects blood samples were drawn every 15 minutes for radioimmunoassay of motilin and somatostatin. After two phase 3s of the migrating motor complex, 6 mg of sumatriptan was administered subcutaneously. Recording continued until two more phase 3s had occurred. RESULTS: Sumatriptan induced a premature phase 3 in the jejunum after a median of 10 (8) minutes. The duration of the migrating motor complex cycle was shortened at the expense of phase 2. After sumatriptan, plasma somatostatin concentrations were reduced and gastric phase 3s were suppressed, although median motilin concentrations and the occurrence of plasma motilin peaks were not affected. Phase 3s of the migrating motor complex preceding sumatriptan were associated with motilin peaks, while phase 3s after sumatriptan were not. Furthermore, pretreatment with sumatriptan prevented the induction of a gastric phase 3 by the motilin agonist erythromycin. CONCLUSIONS: Administration of the 5HT1P receptor agonist sumatriptan induces a premature intestinal phase 3, suppresses gastric phase 3s, prevents induction of a gastric phase 3 by erythromycin, and reduces plasma somatostatin concentrations.

Adult↗