Antral Contractility Research Articles

Motilin induces gall bladder emptying and antral contractions in the fasted state in humans

Background—Animal studies have shown that motilin affects gall bladder motility. In humans, no effect has been shown, but erythromycin, a motilin receptor agonist, induces gall bladder emptying.Aims—To explore the effect...

DOMPERIDONE IS MORE EFFECTIVE THAN CISAPRIDE IN THE TREATMENT OF GASTRIC EMPTYING DELAY AND GASTRIC DYSRHYTHMIAS IN CHILDREN WITH DIABETES MELLITUS.

5 Gastric emptying (GE) delay and gastric electrical abnormalities are often described in patients with diabetes mellitus. These abnormalities can produce dyspeptic symptoms and contribute to poor glycemic control. We wished to compare the effects of two prokinetic drugs, cisapride (CIS) (0.6 mg/kg/day, tid) and domperidone (DOM) (0.9 mg/kg/day, tid) in insulin dependent diabetes mellitus (IDDM) children with GE delay and gastric dysrhythmias, without autonomic neuropathy. Of 36 patients included into the study, 30 (median age: 9 years, range: 4-15 years) completed the trial. Before and at the end of the trial (4 weeks) we measured dyspeptic scoring system (vomiting, early satiety, abdominal pain, fullness; score: 0 = absent; 2 = occasionally, slight; 4 = occasionally, moderately severe; 6 = often, markedly severe), GE time of a mixed solid-liquid meal with ultrasonography of the antral area and cutaneous electrogastrography (EGG). The EGG and GE time were measured during the same session. The EGG variables were:% of normal electrical rhythm (2-4 cycles per minute [cpm]),% of tachygastria (>4 cpm), fed-to-fasting ratio of the dominant EGG power (i.e. the power of the EGG at the dominant frequency, a variable commonly thought to be the electrical counterpart of antral contractility). Fifteen patients received CIS, 15 DOM. The two groups were comparable for symptom score, degree of gastroparesis and EGG abnormalities.Results (mean±SD):TableConclusion: in children with IDDM and gastroparesis treatment with DOM is more effective than CIS in improving both dyspeptic symptoms and gastric emptying. Since gastric dysrhythmias are usually associated with impaired contractility, normalization of gastric electrical activity by DOM seems to play a critical role in ameliorating GE time.

Which form of erythromycin should be used to treat gastroparesis? A pharmacokinetic analysis.

Erythromycin is a macrolide antibiotic that exhibits prokinetic effects. It has been shown to enhance antral contractility and accelerates gastric emptying rates, primarily by stimulating motilin receptors. To determine the optimal dosage form of erythromycin for use as a prokinetic agent. Eight normal volunteers and three patients with documented gastroparesis ingested 250 mg erythromycin in tablet. suspension and intravenous forms. Serum erythromycin levels were determined at frequent intervals. These data were plotted vs. time and analysed for lag time, time to maximum concentration (tmax), maximum concentration (Cmax) and bioavailability (F). The absorption kinetics of the erythromycin suspension was notable for short lag times and early tmax, while lag times and tmax were delayed with the tablet form. Median lag time was 15 min for the suspension vs. 90 min for the tablet (P < 0.005). Median tmax for the suspension was 45 min vs. 180 min for the tablet (P < 0.005). A non-significant decrease in F was seen with the suspension compared to the tablet (P = 0.12). Based on the kinetic data from this study, erythromycin suspension is the ideal dosage form for administration of this drug as a prokinetic agent.

Effect of octreotide on gastric and small bowel motility in patients with gastroparesis.

Octreotide has been shown to have effects on gastric and small bowel motility with implications for its role in treating patients with upper gastrointestinal dysmotility syndromes. Our aim was to investigate the effect of octreotide on antral and small bowel motility in patients with gastroparesis. Upper gastrointestinal manometry was carried out continuously for a period of 30 h in 11 patients with gastroparesis. The spontaneous migrating motor complex (MMC) in the fasting state and octreotide-induced MMCs were characterized and compared with regard to site of origin, duration of phase III, amplitude of phase III and propagation velocity of the MMC along the gut. The 2-h postprandial motility index was compared after a control meal as well as after a 100 microg octreotide administration. In all 11 gastroparetic patients, octreotide induced a phase III-like activity front within minutes after administration and this primarily originated in the small bowel (86% of activity fronts compared with 32% of fronts originating in the small bowel prior to octreotide administration (P < 0.004)). Gastric initiation of these activity fronts dramatically decreased after octreotide administration, occurring in 68% of activity fronts prior to octreotide administration and 14% of occasions after octreotide injection (P < 0.05). The postprandial antral motility index was markedly reduced after octreotide administration (11.33 +/- 0.39 vs. 7.96 +/- 0.76, P < 0.0003) and octreotide re-established a motility pattern during the postprandial period that was similar to that normally seen in the interdigestive state. The octreotide-induced phase III activity fronts appeared at a higher frequency and had a higher propagative velocity compared to the spontaneous phase III fronts in the fasting state (9.27 +/- 0.82 vs. 5.56 +/- 0.81 cm/min, P < 0.05). We conclude that octreotide's marked inhibitory effect on antral contractility may serve to worsen clinical symptoms in patients with gastroparesis and therefore this agent should not be given in the periprandial period. Those gastroparetic patients with associated small bowel dysmotility and diarrhoea from bacterial overgrowth may benefit from the nocturnal administration of octreotide because of its stimulatory effect of phase III MMC activity as well as its known inhibitory effect on small bowel secretions.

Effect of gastric acid suppressants on human gastric motility

Background—The effect of histamine H2receptor antagonists on gastric emptying is controversial.Aims—To determine the effects of ranitidine, famotidine, and omeprazole on gastric motility and emptying.Patients and methods—Fifteen normal subjects underwent simultaneous...

Ranitidine and nizatidine stimulate antral smooth muscle contractility via excitatory cholinergic mechanisms.

Histamine type 2 receptor antagonists (H2RAs) have been found to alter gastric motility. The aims of this study were to determine if H2RAs affect antral contractility in vitro and the mechanism of this effect. Guinea pig antral muscle strips were pinned in an organ bath after removing the mucosa, and circular muscle tension was measured using an isometric force transducer. Gastric myocytes were isolated from guinea pig stomach using collagenase digestion, and cell lengths were measured using an image analysis system. In muscle strips, ranitidine and nizatidine increased the amplitude of spontaneous phasic antral contractions in a concentration-dependent fashion with threshold concentrations of 5 microM. The order of potency for the H2RAs was ranitidine = nizatidine >> cimetidine > famotidine. The contractile effects of ranitidine and nizatidine were reduced, but not abolished, by tetrodotoxin and omega-conotoxin GVIA and nearly abolished by atropine. In isolated cells, ranitidine and nizatidine, but not famotidine or cimetidine, induced concentration-dependent cell shortening, with maximal shortening at 10 microM. These contractile effects of ranitidine and nizatidine in isolated cells were inhibited by atropine. Ranitidine and nizatidine increase antral contractility; this effect appears to be mediated by an interaction between ranitidine and nizatidine on cholinergic pathways with both direct effects on smooth muscle cholinergic receptors and indirect effects by increasing cholinergic neurotransmission.

Erythromycin Elicits Opposite Effects on Antro-Bulbar and Duodenal Motility: Analysis in Diabetics by Cineradiography

We have previously demonstrated by cineradiography analysis that erythromycin (Ery) increases antral contractility and antropyloric coordination in diabetics. The aim of this study was to further characterize antro-bulbar and duodenal motility after Ery iv administration. Fourteen diabetic patients (mean age 61.2 years) were randomly allocated to receive either 100 or 500 mg of Ery intravenously 4 hours after a standard solid liquid meal. After ingestion of a barium sulfate suspension, a series of 15 fluorographic plates (one every two seconds) was performed. The same procedure was repeated twice for each subject with a delay of 3 days once before and once after Ery. Antral, bulbar and duodenal areas and evolution diagrams were calculated in baseline conditions and after Ery administration using a graphic table connected to a microcomputer. No differences were found between the two doses of the drug. Ery significantly decreased antral (1284 ± 268 mm 2 vs 704 ± 181 mm 2; P < 0.01) and bulbar areas (127 ± 26 mm 2 vs 73 ± 21 mm 2; P < 0.01). In contrast, duodenal areas were significantly increased after Ery (875 ± 112 mm 2 vs 575 ± 112 mm 2; P < 0.01). This study suggests that the known prokinetic effect of Ery on gastric emptying seen in diabetic patients could be related to an increase of motility in the antrum and in the bulb simultaneously with a relaxation in the duodenum.

Evaluation of gastric antral motor performance in patients with dysmotility-like dyspepsia using real-time high-resolution ultrasound.

Although manometric antral hypomotility and delayed gastric emptying have been reported separately in patients with dyspepsia, relationships between symptoms, antral contractility and emptying rate have not been sought. The present study therefore aimed to evaluate, simultaneously, gastric antral excursion characteristics and emptying in a sub-group of patients with severe functional dyspepsia using high-resolution real-time ultrasound. The circumference of the relaxed and contracted antrum was measured at 15-min intervals after ingestion of a 360 mL mixed nutrient meal in 36 chronic dyspepsia patients with symptoms of post-prandial bloating and epigastric distension, and in 25 healthy volunteers. Antral emptying (measured as the rate of decrease in circumference of the relaxed antrum) was slower in patients than normals (P = 0.02). In both groups, the average values for antral excursion were similar but the range of excursion in patients was significantly wider than in controls (F < 0.001), with 11 patients showing values above, and 8 showing values below the normal range. There was no relationship between antral emptying and antral excursion in either patients or volunteers. In conclusion, patients with severe functional dyspepsia show a wide range of antral performance characteristics, suggesting not only that the mechanisms responsible for the control of antral motor function are disturbed but also that the cause of the symptoms and the disturbed antral motor function are probably not directly related.

Erythromycin inhibits rabbit pyloric smooth muscle through neuronal motilin receptors

BACKGROUND & AIMS: Erythromycin's effect in accelerating gastric emptying is attributed primarily to increased antral contractility. The aim of this study was to characterize erythromycin's effect on pyloric muscle. METHODS: Rabbit pyloric muscle strips were studied in vitro. RESULTS: Pyloric muscle strips developed spontaneous phasic contractions with a frequency of 1.9 +/- 0.1 contractions per minute. Erythromycin and motilin had dose-dependent inhibitory effects on pyloric muscle. At the maximal effective dose (50 mumol/L), erythromycin caused cessation of spontaneous contractions for 1.8 +/- 0.2 minutes, decreasing the initial 2-minute motility index to 35% +/- 9% (P < 0.01) of basal. In the presence of tetrodotoxin, both erythromycin and motilin increased pyloric contractility. Motilin tachyphylaxis both in the presence or absence of tetrodotoxin abolished the effects of erythromycin. The inhibitory effect of erythromycin was decreased by NG-nitro-L-arginine methyl ester and the vasoactive intestinal peptide antagonist [4-Chloro-D-Phe6, Leu17]vasoactive intestinal peptide. CONCLUSIONS: These studies suggest that motilin receptors are present on both pyloric muscle and inhibitory neurons to pyloric muscle, that the primary effect of erythromycin on the pylorus is mediated by activating motilin receptors on inhibitory motor neurons, and that both nitric oxide and vasoactive intestinal peptide may mediate the inhibitory effect of erythromycin. (Gastroenterology 1996 Sep;111(3):682-90)

Gastrokinetic effects of erythromycin: myogenic and neurogenic mechanisms of action in rabbit stomach.

The aims of this study were to determine regional differences and the mechanism of gastric contractile effects of erythromycin. Rabbit gastric circular muscle strips were studied in vitro. The threshold dose for erythromycin was significantly less and the maximum contraction greater in the antrum (1 microM and 0.9 +/- 0.3 kg/cm2) than in the fundus (10 microM and 0.3 +/- 0.1 kg/cm2). Erythromycin-induced antral contractions were decreased by motilin tachyphylaxis but unaffected by tetrodotoxin, atropine, hexamethonium, or ondansetron. At a subthreshold dose (0.1 microM), erythromycin increased the frequency, but not the amplitude, of bethanechol (10 +/- 3%)-and substance P-induced (13 +/- 5%) phasic antral contractions. This chronotropic effect was inhibited with tetrodotoxin, atropine, or motilin tachyphylaxis. Erythromycin (10 microM) and motilin (1 microM) enhanced the amplitude of substance P-induced tonic fundic contractions by 38 and 32%, respectively, without effect on bethanechol-induced contractions. In summary, erythromycin contracts antral muscle more potently and forcefully than fundic muscle. Erythromycin increases antral contractility by two mechanisms: an inotropic effect acting on smooth muscle motilin receptors, and, at lower doses, a cholinergic chronotropic effect mediated through neuronal motilin receptors.

Erythromycin effects on gastric emptying, antral motility and plasma motilin and pancreatic polypeptide concentrations in anorexia nervosa.

In primary anorexia nervosa, gastric motility is often impaired and ensuing symptoms further discourage eating. Prokinetic agents have been shown to accelerate gastric emptying in affected patients. This study investigated whether emptying of a radiolabelled semisolid 1168 kJ meal and antral contractility were enhanced by intravenous erythromycin. Eight women and two men with anorexia nervosa (21-46 years, 50-75% of ideal body weight) received 200 mg erythromycin or placebo under crossover double blind conditions. Gastric emptying and antral contractility were recorded scintigraphically for 90 minutes. In addition, plasma motilin and pancreatic polypeptide concentrations were determined. With placebo, antral contractions were of regular 3 cycles/minute frequency. With erythromycin, less frequent and partly arrhythmic long duration contractions set in and emptying was accelerated: after 90 minutes, the activity remaining in the stomach was markedly less than with placebo in all patients (Sign test, p < 0.002). Basal motilin and pancreatic polypeptide concentrations were normal and showed a normal response to the meal in all patients. Motilin concentrations decreased slightly more and pancreatic polypeptide concentrations increased markedly more with erythromycin than with placebo, possibly because the meal reached the intestine earlier. In conclusion, erythromycin accelerated emptying markedly and in most patients induced an antral motor activity characterised by long duration contractions occurring at often irregular intervals.

A Double-Blind Fluoroscopic Study of Cisapride on Gastrointestinal Motility in Patients with Functional Dyspepsia

Twenty patients with functional dyspepsia were referred for radiologic examination and, upon confirmation of a hypomotile stomach, were given either 10 mg cisapride or placebo in a double-blind manner (10 patients per group). The movement of a 250-ml barium meal was assessed by means of television fluoroscopy performed at regular time intervals. Cisapride significantly improved antral contractility and enhanced gastric emptying compared with placebo. Deep peristaltic waves occurred over the entire small bowel, and motility and small-bowel transit time of the barium meal were significantly increased in the cisapride group compared with the placebo group. The study demonstrates that when a carefully defined protocol is observed, fluoroscopy following barium ingestion offers considerable potential in the assessment of gastrointestinal motility.

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

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

Development of gastric antral smooth muscle contractility in newborn rabbits

Muscle strips from newborn and adult rabbits were stimulated with acetylcholine (ACh; receptor activation), potassium (membrane depolarization), and calcium (skinned muscle preparation). The study was designed to determine whether postnatal development is associated with agonist-specific increases in force development or with an overall increase in antral smooth muscle contractility. The results can be summarized as follows. 1) Antral smooth muscle from newborn animals developed less active force than tissues from adult animals when stimulated with ACh. 2) Antral smooth muscle from newborn animals developed less active force than tissues from adult animals when stimulated with potassium. 3) Skinned muscle preparations from newborn animals developed less active force than skinned muscle fibers from adult animals when stimulated with calcium. The data suggest that the overall contractility of antral smooth muscle from the newborn is less than that of the adult and that the difference can be attributed, at least in part, to factors past the level of the membrane. The study does not rule out the possibility that differences might also exist with respect to the availability or mobilization of calcium.

Where Do We Stand on Gastric Motility?

This review deals with several aspects of gastrointestinal motility. It attempts to relate basic knowledge to clinically relevant issues. The review is organized around specific contractile patterns and tasks in the gastrointestinal region that are grouped into three broad categories: tonic contractility of the stomach, antral phasic contractility, and resistance of the gastric outlet. There is also a section dealing with the evaluation of gastric motor function for diagnostic purposes describing the technologic means for investigating motility disorders in patients presenting with different clinical syndromes. In this section there is also reference to the criteria to be used in interpretation of the results and practical advice on the use of each test. Finally, the review deals with the issue of treatment of gastric motor disorders, comprising both dietary and pharmacologic approaches.

Effects of stimulation of the hypothalamic area on pancreatic exocrine secretion in dogs

The effects of electrical or chemical (0.1 M dl-homocysteic acid) stimulation of the hypothalamus on pancreatic exocrine secretion were studied in chloralose-anesthetized and hemispherectomized dogs whose pyloric sphincter had been ligated. Excitatory pancreatic flow responses with frequently increased antral contractility and small changes in blood pressure were induced by stimulation of the ventral and dorsal portions of the anterior hypothalamic area, the lateral part of the middle hypothalamus, and the mamillary body. The inhibitory pancreatic responses with reduced antral and corpus contractility and elevated blood pressure were elicited by stimulation of the posterior hypothalamic area, the middle portion of the anterior hypothalamus and the most dorsal area of the hypothalamus. Both excitatory and inhibitory responses were obtained even in dogs with cervical cord transection. The excitatory responses and some of the inhibitory ones were abolished by vagotomy or atropine, but some inhibitory responses remained even after vagotomy. These results indicate that hypothalamic stimulation induced both excitatory and inhibitory responses in pancreatic exocrine secretion via the vagus and other routes.

Intracerebroventricular pressure inhibits gastric antral and duodenal contractility but not acid secretion in conscious rabbits

Acute nausea characteristically accompanies head injury or increased intracranial pressure, or both. The etiology of this symptom is unclear. We studied the effect of increased intracranial pressure on gastric antral and duodenal contractility and gastric acid secretion in conscious rabbits. Intracerebroventricular pressure was maintained at 3, 8, or 13 cmH2O using normal saline perfused into the lateral cerebral ventricle and gastric antral and duodenal contractility was monitored using chronically implanted strain gauge force transducers. Gastric acid secretion was measured in a separate group of rabbits with chronically implanted gastric cannulas. Increased intracerebroventricular pressure (13 cmH2O) resulted in an immediate suppression of the amplitude of gastric and duodenal contractions by >80% and >60%, respectively. After normalization of intracerebroventricular pressure, the contractile pattern returned to basal levels. Intravenous bolus injection of bethanechol reversed the suppression of gastric antral contractility induced by increased intracranial pressure. Increased pressure for 2 h did not modify gastric acid output as compared with normal pressure controls, whereas atropine significantly inhibited and histamine stimulated gastric acid secretion in the same animals maintained at normal pressure. These results demonstrate that acutely increased intracranial pressure rapidly and reversibly inhibits gastric and duodenal motor function in conscious rabbits.

Gastric emptying and antral motility in reflux esophagitis: Effect of oral metoclopramide

The gastric emptying of the liquid phase of a meal and the fasting antral contractility were studied in 13 patients with reflux esophagitis and in 9 age-matched control subjects. Gastric emptying half-time (t1/2) in reflux esophagitis patients was no different from that of control subjects (P < 0.30). Antral contractility (number of antral contractions and the cumulative antral activity), however, was lower in reflux esophagitis patients than in control subjects (P < 0.001). Oral metoclopramide (15 mg) accelerated gastric emptying, increased the number of antral contractions as well as the cumulative antral activity in patients with reflux esophagitis (P < 0.001). However, it only increased the cumulative antral activity in normal subjects (P < 0.01). These results suggest that metoclopramide may be potentially beneficial to reflux esophagitis patients by reducing the volume of gastric contents available for gastroesophageal reflux.