Cholinergic effects on human gastric motility

BACKGROUND: Cholinergic regulation of chronotropic (frequency) and inotropic (force) aspects of antral contractility and how these impact on gastric emptying are not well delineated. AIMS: To determine the effects of cholinergic stimulation and inhibition on myoelectric, contractile, and emptying parameters of gastric motility. METHODS: Ten normal subjects underwent three studies each, using simultaneous electrogastrography (EGG), antroduodenal manometry, and gastric emptying with dynamic antral scintigraphy (DAS). After 30 minutes of baseline fasting manometry and EGG, subjects received saline intravenously, atropine (0.6 mg then 0.25 mg/hour intravenously), or bethanechol (5 mg subcutaneously). This was followed by another 30 minutes' recording and by three hours of postprandial recording after ingestion of a technetium-99m labelled solid meal. RESULTS: During fasting, atropine decreased, whereas bethanechol increased, the antral manometric motility index and EGG power. Postprandially, atropine decreased the amplitude of antral contractions by DAS, decreased the postprandial antral manometric motility index, and slowed gastric emptying. Atropine caused a slight increase in postprandial frequency of antral contractions by DAS and gastric myoelectrical activity by EGG. Bethanechol slightly increased the amplitude, but slightly decreased the frequency of antral contractions by DAS and decreased the frequency of gastric myoelectrical activity by EGG, with no significant increase in the motility index or gastric emptying. CONCLUSIONS: Cholinergic antagonism with atropine reduces antral contractility and slows gastric emptying. Cholinergic stimulation with bethanechol increases antral contractility, but decreases the frequency of antral contractions, without altering the antral motility index or gastric emptying.     

Intravenous cisapride accelerates delayed gastric emptying and increases antral contraction amplitude in patients with primary anorexia nervosa

Delayed gastric emptying is common in primary anorexia nervosa. We investigated in 12 patients whether gastric emptying could be accelerated by the prokinetic drug cisapride. Patients were studied on two occasions 1 wk apart and received, under random double-blind conditions, 8 mg of cisapride and placebo intravenously. Gastric emptying of an isotopically labeled semisolid meal and antral motor activity were measured using a dual-headed gamma-camera for 50 min. Emptying was significantly slower (half-emptying time, 50-191 min; median, 121 min) than in 24 healthy volunteers (half-emptying times, 21-119 min; median, 47 min). Cisapride accelerated emptying significantly (p less than 0.001; half-emptying time after cisapride, 22-80 min; median, 42 min). Antral contraction amplitude increased and contraction frequency decreased significantly (p less than 0.001), whereas the propagation velocity of contractions remained unchanged. We concluded that intravenous cisapride accelerates gastric emptying and increases antral contraction amplitude in patients with anorexia nervosa. Whether or not these effects can prove beneficial in diminishing the patients' symptoms and in helping them to gain weight can only be answered from studies involving long-term treatment with cisapride.     

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.     

Erythromycin accelerates gastric emptying by inducing antral contractions and improved gastroduodenal coordination.

Erythromycin has been shown to act as a motilin agonist by binding to motilin receptors on gastrointestinal smooth muscle and to improve the severely impaired gastric emptying in patients with diabetic gastroparesis. To elucidate the motor pattern that accounts for this accelerated emptying, the effect of 200 mg erythromycin vs. placebo on postprandial motility of the stomach and the upper small intestine was examined in 13 normal subjects. Erythromycin significantly increased the amplitude of the antral contractions during the 2-hour postprandial study period (maximal difference in mean amplitude of distal antral contractions between erythromycin and placebo recorded from 80 to 90 minutes after meal: 123 +/- 17 vs. 44 +/- 12 mm Hg; P less than 0.005). The total number of antral contractions was not affected, but the contractions could be recorded manometrically higher up in the stomach after erythromycin than after placebo (9-12 vs. 3-6 cm above the pylorus). Antroduodenal coordination was significantly improved during the first postprandial hour, and the first normal phase 3 of the migrating motor complex, indicating the reappearance of fasting motility, occurred earlier after erythromycin than after placebo (128.3 +/- 14.3 vs. 173.4 +/- 16.1 minutes; P less than 0.05). These changes in postprandial motility induced by erythromycin may well account for its accelerating effect on gastric emptying.     

Gastric emptying and its relationship to antral contractile activity.

Gastric emptying and antral contractile activity were simultaneously measured in 3 dogs with gastric and duodenal fistulas. Contractile activity was monitored by two force strain gauge transducers on the serosal surface of the antrum of 2 dogs and a single strain gauge transducer on the serosal surface of both the antrum and fundus of the 3rd dog. Both the frequency and force (motility index) of antral contractions were determined for each 1 min period. Gastric emptying and contractile activity were recorded and compared minute by minute with test meals (154 mM saline) of 60, 120, 240, and 480 ml. Although the rate of gastric emptying increased with the frequency and force of antral contractions, up to 67 ml min-1 (mean 6.9 ml min-1) were emptied without measurable antral contractile activity and 0 to 96 ml min-1 (mean 19.4 ml min-1) were emptied during maximal antral activity (minute motility index greater than 119 mm). Antral contractile activity increased with the size of the test meal and decreased expoentially with the rate of gastric emptying. Fundal contractile activity was generally absent during the test meal. These studies suggest that although the antrum has a significant role in the emptying of liquids, other undefined factors may modify its effect on gastric emptying.     

Continuous monitoring of the effect of pentagastrin on gastric emptying of solid food in man.

By continuous monitoring of a solid meal labelled with a radiopharmaceutical it has been possible to determine the effects of drugs on gastric emptying and motility during a single study. Predictably hyoscine delayed, and bethanechol increased, the rate of gastric emptying. Pentagastrin initially produced marked antral activity resulting in a physiological stricture and subsequent delay in the overall rate of gastric emptying. Fundal motility was unaffected though reflux from the antrum occurred.     

Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans. METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers.     

Effects of ginger on gastric emptying and motility in healthy humans

OBJECTIVE: Ginger has been reported to improve upper gastrointestinal symptoms. Little information about the effects of ginger on gastric motor function, exists, however. Our aim was to investigate the effects of ginger on gastric emptying, antral motility, proximal gastric dimensions, and postprandial symptoms. METHODS: Twenty-four healthy volunteers were studied twice in a randomized double-blind manner. After an 8 h fast, the volunteers ingested three ginger capsules (total 1200 mg) or placebo, followed after 1 h by 500 ml low-nutrient soup. Antral area, fundus area and diameter, and the frequency of antral contractions were measured using ultrasound at frequent intervals over 90 min, and the gastric half-emptying time was calculated from the change in antral area. Gastrointestinal sensations and appetite were scored using visual analog questionnaires. Data are expressed in terms of mean+/-standard error. RESULTS: Antral area decreased more rapidly (P<0.001) and the gastric half-emptying time was less after ginger than placebo ingestion (13.1+/-1.1 vs. 26.7+/-3.1 min, P<0.01), whereas the frequency of antral contractions was greater (P<0.005). Fundus dimensions did not differ, and there was no significant difference in any gastrointestinal symptoms. CONCLUSION: Ginger accelerates gastric emptying and stimulates antral contractions in healthy volunteers. These effects could potentially be beneficial in symptomatic patient groups.     

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 subjectsunderwent simultaneous antroduodenal manometry, electrogastrography(EGG), and gastric emptying with dynamic antral scintigraphy (DAS).After 30 minutes of fasting manometry and EGG recording, subjectsreceived either intravenous saline, ranitidine, or famotidine, followed by another 30 minutes recording and then three hours of postprandial recording after ingestion of a radiolabelled meal. Images were obtainedevery 10-15 minutes for three hours to measure gastric emptying andassess antral contractility. Similar testing was performed afteromeprazole 20 mg daily for one week.
Results—Fasting antral phase III migrating motorcomplexes (MMCs) were more common after ranitidine (9/15 subjects,60%), famotidine (12/15, 80%), and omeprazole (8/12, 67%) comparedwith placebo (4/14, 29%; p<0.05). Postprandially, ranitidine,famotidine, and omeprazole slowed gastric emptying, increased theamplitude of DAS contractions, increased the EGG power, and increasedthe antral manometric motility index.
Conclusions—Suppression of gastric acid secretionwith therapeutic doses of gastric acid suppressants is associated withdelayed gastric emptying but increased antral motility.

Keywords:gastric motility; gastric emptying; histamineH₂ receptor antagonists; proton pump inhibitors; gastricacid secretion; scintigraphy

     

Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

Background: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide‐stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans. Methods: Ten healthy male volunteers (21–28 years) participated in a placebo‐controlled, double‐blind, cross‐over study. In random order and on two separate days each volunteer ingested either 50?mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure gastric emptying and postprandial frequency of antral contractions. Results: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. Conclusion: A single dose of 50?mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers.     

Different effects of atropine and cimetropium bromide on gastric emptying of liquids and antroduodenal motor activity in man

Atropine (1 mg intravenously) and a new antimuscarinic compound, cimetropium bromide (5 mg intravenously), as well as placebo (physiological saline) were tested for their effects on gastric emptying and antroduodenal motility in healthy humans. In a first single-blind cross-over study, the emptying rate was assessed in 12 subjects by measuring paracetamol absorption. In a second single-blind parallel-group study, antroduodenal motor activity was measured in 20 subjects through four perfused open tip catheters with orifices positioned in the antroduodenal region. Atropine, unlike cimetropium bromide, significantly delayed gastric emptying. Antral and duodenal motility index was reduced significantly by atropine, but not by cimetropium bromide. Heart rate significantly increased only after atropine. Three subjects taking atropine complained of dry mouth and one of blurred vision. In conclusion, the results of these studies show that atropine, unlike cimetropium bromide, strongly inhibits gastric emptying of liquids and reduces antroduodenal motor activity in man.     

Slow gastric emptying induced by high fat content of meal accelerated by cisapride administered rectally

The evaluation of agents potentially accelerating gastric emptying in gastric stasis syndromes is time-consuming. Since a previous study showed that emptying is slowed after antecedent fat ingestion and intravenous cisapride abolishes this effect, we investigated whether emptying delayed by fat incorporated into a meal is reversed by cisapride and thus could serve as a model for such evaluations. Twelve healthy males received, under double-blind conditions, 30 mg cisapride rectally or placebo, and 3 hr thereafter a semisolid meal of low (9.2 g) or high (37.9 g) fat content. The sequence of combinations placebo/low-fat meal, placebo/high-fat meal, and cisapride/high-fat meal was randomized. Gastric emptying and antral motility were recorded scintigraphically. After placebo/high-fat, emptying was significantly slower (P<0.05) than after placebo/low-fat. After cisapride/high-fat, emptying was significantly faster (P<0.01) than after placebo/high-fat and similar to that after placebo/low-fat. Antral motility was little affected. The slow emptying of a high-fat meal thus seems a suitable model for the evaluation of prokinetic drug effects.     

Oral administration of loxiglumide (CCK antagonist) inhibits postprandial gallbladder contraction without affecting gastric emptying

The effect of a single oral dose of loxiglumide, a cholecystokinin antagonist, on postprandial gallbladder contraction and on gastric emptying was evaluated in humans. Following a 12-hr fasting period, two tablets of loxiglumide (400 mg each) or placebo was administered on different days, in random order and in a double-blind fashion to 10 healthy volunteers 15 min before the ingestion of a 1050-kcal standard meal. Gallbladder and antral volumes were measured by real-time ultrasonography in basal conditions and at fixed time intervals after the meal. Oral loxiglumide administration was followed by a total inhibition of the gallbladder contraction for 60 min after the end of the meal ingestion. Thereafter, up to the end of the study period, gallbladder volume was larger than that of the placebo study (at 300 min after the meal 2.7±1.6 ml after placebo and 8.2±3.5 ml after loxiglumide; P<0.008). No difference between placebo and loxiglumide was found in the antral volumes at any time interval (postprandial 63.5±16.5 ml after placebo and 59.4±24 ml after loxiglumide; at 300 min after the meal 20.8±13.3 ml after placebo and 18.9±9.5 ml after loxiglumide). In conclusion, a single oral dose of loxiglumide at the dose of 800 mg can inhibit postprandial gallbladder contraction without affecting gastric emptying. It would therefore appear that in man endogenous CCK, released after a solid-liquid, caloric, nutrient-balanced meal, plays a major role in the contraction of the gallbladder but does not affect gastric emptying.     

Quantitation of Duodenogastric Reflux and Antral Motility by Color Doppler Ultrasonography: Study in Healthy Volunteers and Patients with Gastric Ulcer

Fujimura J, Haruma K, Hata J, Yamanaka H, Sumii K, Kajiyama G. Quantitation of duodenogastric reflux and antral motility by color Doppler ultrasonography. Study in healthy volunteers and patients with gastric ulcer. Scand J Gastroenterol 1994;29:897-902.

Background: Our objective was to develop a simple, noninvasive method for evaluating duodenogastric reflux, along with antral motility and gastric emptying of a liquid meal. Methods: Antral motility and gastric emptying were measured by ordinary ultrasonography after a meal of 400 ml consommé. Duodenogastric reflux was evaluated by means of color Doppler. In a preliminary in vitro study we demonstrated that the test meal (consommé) contained oil particles suitable as a marker for color Doppler. We then investigated duodenogastric reflux, antral motility, and gastric emptying of a liquid meal in 43 asymptomatic healthy volunteers and in 24 patients with gastric ulcer. Results: This approach was feasible in 65 (97.0%) of the 67 subjects studied. Duodenogastric reflux was demonstrated in 26 (61.9%) of the 42 healthy volunteers and in 20 (87.0%) of the 23 patients with gastric ulcer. The frequency of the duodenogastric reflux and the reflux index were significantly increased in patients with gastric ulcer as compared with asymptomatic healthy volunteers. Gastric emptying and the motility index of antral contractions were significantly decreased in patients with gastric ulcer as compared with asymptomatic healthy volunteers. Conclusions: Ultrasonography with color Doppler is useful for evaluating abnormalities of gastroduodenal motility and can be used to understand the pathogenesis of such disorders.     

Effect of hyoscine N-butylbromide on gastroesophageal reflux in normal subjects and patients with gastroesophageal reflux disease

OBJECTIVES: Recent studies have shown that atropine reduces gastroesophageal reflux in normal subjects and patients with gastroesophageal reflux. The aim of the study has been to assess the effects of an atropine derivative, hyoscine N-butylbromide in normal subjects and patients with gastroesophageal reflux disease by recording esophageal and gastric pH-metry for a 24-h period. METHODS: Ten normal subjects and 10 patients with gastroesophageal reflux disease were evaluated. PH-metry was performed using two glass pH flexible probes with distal incorporated electrodes. The two catheters were introduced nasally under fluoroscopy. One probe was positioned in the gastric body; the other was placed 5 cm above the lower esophageal sphincter which had been evaluated manometrically before the study. Recording lasted without interruption for 48 h. Patients and normal subjects were assigned to receive hyoscine N-butylbromide (10 mg p.o. t.i.d.) for 24 h followed by a placebo for another 24 h or vice versa in a random manner. The pH was analyzed for a total number of acid refluxes and percentage of the period with pH <4 in the esophagus and the mean gastric pH in 24 h, before and after treatment with hyoscine N-butylbromide. RESULTS: The number of reflux episodes was significantly greater with hyoscine N-butylbromide in comparison with a placebo in patients with gastroesophageal reflux disease and normal subjects (p < 0.02). The percentage of time with pH <4, was also significantly greater in patients with gastroesophageal reflux disease and in controls (p < 0.05). The mean 24-h gastric pH after hyoscine N-butylbromide was not different from placebo in gastroesophageal reflux disease and controls. CONCLUSIONS: Hyoscine N-butylbromide, an anticholinergic agent, increases the total number of esophageal acid refluxes in patients with gastroesophageal reflux disease and in controls, therefore it is not recommended in the treatment of gastroesophageal reflux disease.     

Evaluation of gastric emptying and motility in diabetic gastroparesis with magnetic resonance imaging: effects of cisapride

OBJECTIVE: The motor mechanisms that underlie both slow gastric emptying in diabetic gastroparesis and its acceleration by cisapride are poorly understood. We have recently shown that magnetic resonance imaging (MRI) allows concurrent evaluation of both gastric emptying and regional gastric motility. METHODS: Emptying and motility were measured in eight diabetic patients with previously demonstrated delayed gastric emptying using a rapid MRI technique during oral administration of cisapride and placebo. Studies were performed in a double blind fashion and each patient acted as his own control. Subjects were studied supine for 120 min in a 1.5 Tesla MRI scanner after ingestion of 500 ml of 10% Intralipid. Gastric emptying corrected for the volume of secretions was determined every 15 min using transaxial scans. Each transaxial scan was followed by 120 coronal scans at 1 s intervals. Coronal scans were angled to provide simultaneous imaging of the proximal and distal stomach. MRI studies were also performed in seven diabetic patients with normal emptying who served as disease controls. RESULTS: Emptying was slower in the gastroparetic patients (t(1/2): 124 +/- 10 min) compared to patients with normal emptying (81 +/- 9 min, p < 0.05). Cisapride accelerated gastric emptying (74 +/- 5 vs 124 +/- 10 min) in patients with gastroparesis. The contraction amplitudes in the proximal stomach of gastroparetic patients were increased during cisapride treatment (17.2% +/- 1.8% vs 13.2% +/- 0.6%; p < 0.02), whereas antral contraction frequency, amplitude, and velocity were unchanged. CONCLUSIONS: We conclude that cisapride-induced acceleration of liquid gastric emptying in diabetic gastroparesis does not appear to result from changes in antral contractility, but may be related to changes in proximal gastric tone or gastric outlet resistance.     

Effect of ginger on gastric motility and symptoms of functional dyspepsia

AIM:To evaluate the effects of ginger on gastric motility and emptying,abdominal symptoms,and hormones that influence motility in dyspepsia.METHODS:Eleven patients with functional dyspepsia were studied twice in a randomized double-blind manner.After an 8-h fast,the patients ingested three capsules that contained ginger(total 1.2 g) or placebo,followed after 1 h by 500 mL low-nutrient soup.Antral area,fundus area and diameter,and the frequency of antral contractions were measured using ultrasound at frequen...     

Effect of somatostatin on bethanechol-stimulated gastric acid secretion and gastric antral motility in dogs with gastric fistula

The purpose of the present study was to evaluate the effect of somatostatin on gastric acid secretion and gastric antral motility in conscious dogs with gastric fistula. Infusion of bethanechol stimulated dose-dependently acid secretion, whereas the frequency and strength of antral motility was maintained at a high level. Somatostatin inhibited dose-dependently the stimulated acid secretion, whereas the effect on antral motility was more complex, acting especially on the amplitude of the contractions. The effects of somatostatin were not altered by using alpha-adrenergic, beta-adrenergic, dopaminergic, and serotonergic blocking drugs. The dose-response kinetics with four doses of bethanechol with and without somatostatin showed inhibition of a non-competitive type for gastric acid secretion and of a competitive type for antral motility with regard to amplitude.     

Inhibitory Effects of Sildenafil on Small Intestinal Motility and Myoelectrical Activity in Dogs

Previous studies have shown that sildenafil inhibits the esophageal motility in both humans and animals. The aim of this study was to investigate the effects of sildenafil on intestinal myoelectrical activity and motility. The study was composed of 2 experiments and performed in 7 healthy female dogs with a duodenal cannula 20 cm beyond pylorus (19–26 kg). The first experiment was designed to study the effects of sildenafil on intestinal myoelectrical activity and it included 2 sessions each consisting of 30-minute baseline, 15-minute posttreatment (placebo or 100 mg sildenafil) and 90 minutes after a liquid meal. Intestinal myoelectrical activity was recorded during the entire experiment period. The second experiment was aimed to investigate the effect of sildenafil on intestinal motility and was performed immediately after a solid meal. Intestinal motility was measured by a manometric catheter inserted into the small intestine via the duodenum cannula for 30 minutes at baseline and 60 minutes after sildenafil. Sildenafil significantly reduced the amplitude but had no effect on the frequency and regularity of the intestinal myoelectrical activity. Sildenafil significantly inhibited postprandial intestinal contractions. Although the frequency of the contractions was not altered, the mean area under the curve was significantly reduced during the first 30 minutes (P < .03) and second 30 minutes after sildenafil (P < .03); the power of intestinal contractile activities was also significantly reduced during the first 30 minutes (P < .0004) and second 30 minutes after sildenafil (P < .0003) in comparison with baseline. In conclusion, sildenafil inhibits the amplitude of both intestinal contractile activity and intestinal slow waves.     

Effect of single dose of oral erythromycin on gastric and gallbladder emptying

To evaluate the effects of a single oral dose of erythromycin on gastric and gallbladder emptying, 10 volunteers, without a known history of gastrointestinal disease, were investigated. Erythromycin stearate (500 mg) or placebo was given on separate mornings 30 min before a standard solid meal in a randomized, double-blind, crossover study. Gastric and gallbladder emptying rates were simultaneously evaluated by means of real-time ultrasonography. Gastric antral area and gallbladder volume were determined before the meal and 30, 60, 120, 180, 240, and 300 min after commencing eating. Erythromycin, compared to placebo, significantly accelerates and increases the degree of both gastric and gallbladder emptying. As previously reported for intravenous and chronic oral assumption, also a single dose of oral erythromycin is able to accelerate gastric and gallbladder emptying in normal human subjects.MIS: Member of Institute of Statisticians.This work was partially supported by a grant from Ministero dell'Universita e della Ricerca Scientifica e Tecnologica (fondi 60%).