Inhibition of gastric acid secretion normalizes interdigestive motor activity in the stomach in dogs

Recently, intragastroduodenal acidity has been shown to play an important role in interdigestive gastrointestinal motility. In this study, gastrointestinal motility and intragastric pH changes were monitored simultaneously in dogs, to characterize 1) the relationship between intragastric pH changes and IMC, and 2) the effects of intragastric acidity on motilin-induced phase III contractions in the gastric antrum by using secretagogues and an H2 receptor antagonist (cimetidine). As a result, intragastric pH showed periodic changes with gastric IMC in conscious dogs. Furthermore, motilin-induced gastric phase III contractions were inhibited by gastric acidification. But inhibition of gastric acid secretion by cimetidine normalized both the motor index and migration of the contractions. In conclusion, gastric acid secretion may influence the sensitivity to motilin of the stomach, and play an important role in the regulation of interdigestive gastric motility.     

In Dyspeptic Patients without Gastric Phase III of the Migrating Motor Complex,Helicobacter pylori Eradication Produces no Short-term Changes in Interdigestive Motility Pattern

Background: The relationship between Helicobacter pylori infection and interdigestive gastroduodenal motility in functional dyspepsia is still uncertain. Recent data from a large series documented that in dyspeptic patients without gastric phase III of the interdigestive migrating motor complex (MMC), the prevalence of bacterial infection was significantly higher. Since most H. pylori-positive dyspeptic patients have coexisting chronic gastritis, whether or not dyspepsia per se rather than bacterial colonization or chronic inflammation of the gastric mucosa may account for the observed interdigestive motility pattern is unknown. Our aim was to compare the interdigestive gastroduodenal motility pattern and dyspeptic symptoms before and 1 month after bacterial eradication in 20 H. pylori-positive dyspeptic subjects with chronic non-atrophic gastritis and without gastric phase III of the MMC, who were randomly allocated to receive eradication treatment (n = 10) or not (n = 10). Methods: Upper GI endoscopy with duplicate biopsies in antrum and corpus, 240-min interdigestive gastroduodenal manometric recording and symptoms assessment were performed before and 1 month after the treatments; bacterial eradication was confirmed by 13C-urea breath test. Results: After H. pylori eradication, neither in the incidence of antral and duodenal phase III of MMC nor in the phase II motility index values were any changes observed. Symptomatic improvement was recorded in both groups, with no significant differences between eradicated patients and controls. Conclusions: In dyspeptic patients with chronic non-atrophic gastritis and without gastric phase III of MMC, H. pylori eradication influences neither the interdigestive motility pattern nor the symptoms in the short-term period.     

In dyspeptic patients without gastric phase III of the migrating motor complex, Helicobacter pylori eradication produces no short-term changes in interdigestive motility pattern

BACKGROUND: The relationship between Helicobacter pylori infection and interdigestive gastroduodenal motility in functional dyspepsia is still uncertain. Recent data from a large series documented that in dyspeptic patients without gastric phase III of the interdigestive migrating motor complex (MMC), the prevalence of bacterial infection was significantly higher. Since most H. pylori-positive dyspeptic patients have coexisting chronic gastritis, whether or not dyspepsia per se rather than bacterial colonization or chronic inflammation of the gastric mucosa may account for the observed interdigestive motility pattern is unknown. Our aim was to compare the interdigestive gastroduodenal motility pattern and dyspeptic symptoms before and 1 month after bacterial eradication in 20 H. pylori-positive dyspeptic subjects with chronic non-atrophic gastritis and without gastric phase III of the MMC, who were randomly allocated to receive eradication treatment (n = 10) or not (n = 10). METHODS: Upper GI endoscopy with duplicate biopsies in antrum and corpus, 240-min interdigestive gastroduodenal manometric recording and symptoms assessment were performed before and 1 month after the treatments; bacterial eradication was confirmed by 13C-urea breath test. RESULTS: After H. pylori eradication, neither in the incidence of antral and duodenal phase III of MMC nor in the phase II motility index values were any changes observed. Symptomatic improvement was recorded in both groups, with no significant differences between eradicated patients and controls. CONCLUSIONS: In dyspeptic patients with chronic non-atrophic gastritis and without gastric phase III of MMC, H. pylori eradication influences neither the interdigestive motility pattern nor the symptoms in the short-term period.     

Role of the pancreas in the control of interdigestive gastrointestinal motility

Our aim was to determine if the pancreas regulates the interdigestive motor patterns of the upper gut. Four dogs were prepared with gastric and intestinal manometry catheters and interdigestive (fasting) motility was measured before and after total surgical pancreatectomy. The characteristics of the gastric and intestinal migrating motor complex were very similar before and after pancreatectomy. The time intervals between successive migrating motor complexes in the antrum (145 +/- 11 vs. 135 +/- 15 min, mean +/- SE) or small intestine (133 + 10 vs. 137 +/- 16 min) were not significantly (p greater than 0.4) altered by pancreatectomy, but the antral motility index (the sum of the antral contractions in a 15-min period) was greater after pancreatectomy (53 +/- 6 vs. 27 +/- 4; p less than 0.05). Pancreatectomy led to undetectable plasma concentrations of pancreatic polypeptide, but had no effect on absolute concentrations of plasma motilin or on the cycling of plasma motilin in association with the duodenal migrating motor complex. We conclude that the pancreas and pancreatic polypeptide play little, if any, role in controlling canine interdigestive motility of the upper gut.     

Interdigestive gastroduodenal motility and serum motilin levels in patients with idiopathic delay in gastric emptying

The interdigestive gastroduodenal motor activity and serum motilin levels were studied in 22 dyspeptic patients with markedly delayed gastric emptying not due to diseases known to impair gastroduodenal motility and in 7 control subjects with normal gastric emptying. Motor activity was recorded using a manometric probe positioned in the gastric antrum and in the proximal duodenum, and blood samples for radioimmunoassay of motilin were taken every 15 min during the recording period. The control subjects showed gastroduodenal activity fronts of the migrating motor complex associated with motilin peaks. Almost all patients with delayed gastric emptying showed no activity fronts in the stomach, and only half of them showed activity fronts starting in the duodenum. In these patients a significant reduction in the number of motilin peaks and in the integrated motilin output during the identified peaks was also observed. The results of this study indicate that most dyspeptic patients with idiopathic delay in gastric emptying may also have an alteration in interdigestive gastroduodenal motility, mainly characterized by a lack of gastric activity fronts, associated with an impaired motilin release.     

The relationship between interdigestive gallbladder and gastroduodenal motility in man

The relationship between interdigestive gallbladder and gastroduodenal motility simultaneously with the behavior of plasma motilin and CCK levels in 20 subjects was investigated. We used an infusion catheter method for the measurement of gastroduodenal motility, and real-time ultrasonography for the measurement of gallbladder size. In gastric phase II, the gallbladder contracted with extension of the major axis and shrinking of the minor axis, with its minimum volume being 84% of the volume in phase I. The gallbladder then filled rapidly assuming a sphere-like shape with extension of the minor axis and shrinking of the major axis in gastric phase I. This motility was recognized only during the gastrointestinal interdigestive migrating complex (GI-IMC) cycle, originating in the stomach, and was associated with an increase of motilin levels, it was not seen before or after the intestinal IMC (I-IMC), which originated in the duodenum without contraction of the stomach or an increase of motilin levels. Furthermore no apparent relationship was recognized between CCK and gastric or gallbladder motility. Our findings suggest that gallbladder motility in the interdigestive period has a close relationship with gastroduodenal motility and is related to the appearance of the GI-IMC.     

Effect of octreotide on fasting gall bladder emptying, antroduodenal motility, and motilin release in acromegaly.

Subcutaneous octreotide (Sandostatin) injections lead to gall stone formation in 13-50% of acromegaly patients during one year of therapy. This study explored the effects of octreotide on interdigestive gall bladder emptying, antroduodenal motility, and motilin release. Ambulatory antroduodenal manometry was performed in six acromegaly patients before and after two months of octreotide therapy (100 micrograms thrice daily, subcutaneously). Ultrasonographic gall bladder volume measurements and plasma motilin concentrations were obtained during two migrating motor complex (MMC) cycles. Before octreotide treatment, nine of 26 phase III activities started in the antrum and 17 of 26 in the duodenum whereas during treatment 47 of 48 of phase III activity started in the duodenum (p < 0.05). Before treatment, interdigestive gall bladder emptying (mean (SEM) 39.9 (4.0)% of maximal fasting volume) and plasma motilin peaks preceded antral phase III but not duodenal phase III. During octreotide therapy no significant motilin fluctuation or gall bladder emptying was seen. Fasting gall bladder volume increased from 40.9 (9.1) ml before to 68.0 (14.8) ml (p < 0.05) during octreotide treatment. In conclusion, two months' treatment with octreotide increases the number of duodenal phase III like activity and virtually abolishes antral phase III, plasma motilin peaks, and interdigestive gall bladder emptying. These effects might contribute to the high risk of gall stone formation during longterm octreotide treatment.     

Case Report: Disturbed Initiation of Gastric Interdigestive Migrating Complexes Despite High Plasma Motilin Levels in Patients with Low Gastric pH

It is known that there is a close relationshipbetween serum motilin fluctuation and the initiation ofgastric interdigestive migrating complexes (IMC) (1).The administration of synthetic motilin initiates IMC (2), and antimotilin serum blocks theinitiation of IMC (3). Erythromycin has recently beenshown to be a motilin-receptor agonist (4), and motilinreceptors have been found in the human stomach (5). At present motilin is considered to initiateIMC through both the vagal cholinergic pathway anddirect stimulation of smooth muscle. From the clinicalpoint of view, Labo et al (6) and our group (7) recently reported on the relationship between a lowmotilin concentration and disturbance of IMC in patientswith dyspepsia. On the other hand, little is known aboutthe effect of an abnormally high motilin concentration on gastroduodenal motility. We have found threeoutpatients in our clinic at Gunma University Hospitalwith duodenal ulcer or duodenitis who had disturbedinitiation of IMC despite an abnormally high plasma motilin concentration.     

Location of peptic ulcers in relation to antral and fundal gastritis by chromoendoscopic follow-up examinations

The extent of fundal gastritis and the severity of antral gastritis in patients with duodenal ulcer and coexisting gastroduodenal ulcers were investigated using the endoscopic Congo red test. Forty-two patients with duodenal ulcer were followed-up by chromoendoscopy to investigate the location of gastric ulcers developed during the average observation period of 3.6 years in relation to the changes of fundal and antral gastritis. Duodenal ulcers were usually associated with extensive acid-secreting areas and moderate antral gastritis. In coexisting duodenal and antral ulcers, antral gastritis was usually severe, although fundal gastritis was of the same intensity as that seen with duodenal ulcers. In coexisting duodenal and high-lying ulcers, fundal gastritis was extensive and antral gastritis was severe. Follow-up studies showed that there was a significant relationship between the development of gastric ulcer and the changes of antral and fundal gastritis. Gastric ulcers developed in the antrum or the angulus in patients with duodenal ulcer when antral gastritis became worse, but no fundal gastritis spread. When fundal gastritis spread, ulcers developed in the gastric body. These findings suggested that development of increasing gastritis predicted the development of gastric ulceration and that the locations of gastric ulcer and duodenal ulcer were determined by the extent of fundal gastritis and the severity of antral gastritis.     

The effect of intragastric neutralization on the gastric acid response to antral distension in man.

The gastric acid secretion in response to graded antral distension was determined in healthy subjects and in peptic ulcer patients with water perfusion or alkaline buffer perfusion of the stomach, giving an intragastric pH of 1.8-3.0 and 6.2-8.3 respectively. Intragastric neutralization increased the basal acid secretion in healthy subjects and gastric ulcer patients but did not change the basal acid secretion in duodenal ulcer patients. Distension of the antrum produced the same secretory effect with and without intragastric neutralization: no increased acid response in healthy subjects, a slight acid response in patients with a quiescent duodenal ulcer or a gastric ulcer, and a more pronounced acid response in patients with an active ulcer, amounting to about 30% of the peak acid response to pentagastrin. The results show that: a) the peptic ulcer patients - and particularly patients with an active duodenal ulcer - are more sensitive to the acid secretory effect of antral distension than healthy subjects; b) increasing the intragastric pH above 20 does not enhance the acid response to antral distension; c) the acid secretory effect of antral distension is markedly less in man than the effect observed in the dog.     

Effects of pirenzepine and atropine on gastroduodenal motor patterns in duodenal ulcer patients

The aim of this study was to compare the effects of pirenzepine with those of atropine a non-selective antimuscarinic agent, on gastroduodenal motor patterns in duodenal ulcer patients. Twenty patients were allocated at random to 2 groups of 10 subjects each. The drugs were administered by bolus intravenous injection as equiactive antisecretory doses of 10 mg pirenzepine and 1 mg atropine. Before and 15 min after drug administration all patients underwent a gastroduodenal manometric and reflexogenic study with a specially designed probe and three inflatable latex balloons. Both drugs significantly decreased antral and duodenal pressure, but atropine was much more effective than pirenzepine: 91 +/- 2% verus 54 +/- 9% decrease in the motility index for the antrum and 95 +/- 1% versus 49 +/- 7% for the duodenum (p less than 0.01). The antral motor threshold was not modified by either drug. The results of this study confirm the selectivity of action of pirenzepine on gastric function.     

Gastroduodenal motility in chronic dyspepsia. 1. Interdigestive motility

The interdigestive gastroduodenal motility was studied in 28 patients suffering from chronic dyspepsia and in 15 healthy controls. The pressure activity was recorded using a four-lumen manometric probe positioned in the gastric antrum, the proximal and distal duodenum as well. - The mean cycle duration of the interdigestive myoelectric complex lasted 108 +/- 36 min. in dyspepsia and 81 +/- 30 min. in controls (p less than 0.05). In the antrum this prolongation resulted from a longer duration of phase 1. 7 dyspeptic patients had no activity fronts in the stomach. Both examined groups showed little differences in duodenal motility patterns, except for a significant increase of tonic pressure component during phase 3 activity in dyspepsia. Between gastric emptying time and interdigestive motility no correlation were established.     

Interdigestive gastroduodenal motility in patients with active and inactive duodenal ulcer disease

The interdigestive gastroduodenal motility was studied by means of a manometric probe in 6 patients with active duodenal ulcer and acid hypersecretion, in 6 patients with ulcer disease in remission (inactive) and normosecretion and in 8 healthy subjects with normosecretion. After a basal recording period sufficient to record at least two activity fronts of the migrating motor complex (MMC), an intraluminal infusion of isotonic NaHCO3 was carried out for 180 min in patients with active duodenal ulcer, whereas in patients with ulcer in remission an HCl solution was infused for 180 min. Patients with active duodenal ulcer showed a basal motility with a longer than normal MMC cycle and a shorter than normal activity front, while patients with ulcer in remission showed a cyclic motor activity not significantly different from that of normal subjects. The NaHCO3 infusion in patients with active ulcer restored a near-normal motility, whereas the HCl infusion in patients with ulcer in remission induced a motility similar to that of patients with active ulcer. These data indicate that the increase in gastric acid secretion is responsible for the decrease in frequency and duration of MMC activity fronts, which have the function of cyclically clearing the gastroduodenal lumen. Consequently, acid and bacteria may remain a longer than normal time in contact with the gastroduodenal mucosa, which, in this manner, may be greatly exposed to the risk of peptic lesions.     

Somatostatin in mucosa of stomach and duodenum in gastroduodenal disease.

In order to study the distribution of somatostatin in the upper digestive tract in man, biopsies were taken through endoscopy or at surgery from the fundus, antrum, and duodenal bulb in 15 subjects with no gastroduodenal lesion, 12 patients with severe antral and/or fundic atrophy in the sampling area, 28 patients with an active duodenal ulcer, and 14 patients with a nonmalignant gastric ulcer. The specimens were extracted in 2 N acetic acid and tested for somatostatin content with a specific radioimmunoassay. In the control subjects, the somatostatin concentration (nanograms per milligram of wet weight) was 0.60 +/- 0.12 in the fundus, 1.68 +/- 0.33 in the antrum, and 1.35 +/- 0.30 in the duodenal bulb. Atrophy of the gastric mucosa was associated with a reduction of the somatostatin concentration in the fundus and the antrum. No significant variation was observed in the present series of patients with gastric ulcer. Duodenal ulcer was associated with a reduction of the somatostatin concentration in the antrum (P less than 0.02). These results indicate that somatostatin is widely distributed from fundus to duodenal bulb in adult human subjects, and that lower antral concentrations are observed in patients with duodenal ulcer.     

Serum glucose concentration as a modulator of interdigestive gastric motility

The objective of this study was to examine the effect of serum glucose concentration on interdigestive gastrointestinal motility and plasma motilin levels in humans. Motility studies were performed for a 3-h baseline period and a 3-h test period during which serum glucose levels were maintained with a glucose clamp at 250, 175, 140, or 120 mg/dl. During the basal recording, three phases of the interdigestive migrating motor complex (MMC) were easily recognizable, with a mean cycle duration of 97 +/- 12 min. Plasma motilin levels fluctuated in phase with the MMC. Gastric contractions were nearly absent at a serum glucose level of 250 mg/dl and markedly reduced at 175 and 140 mg/dl. Gastric phase III activity was inhibited during these infusions. Gastric contractions and phase III activity were not affected by glucose infusion at 120 mg/dl. In contrast, the frequency of duodenal phase III activity was unchanged at all levels of glucose infusion. Mean motilin levels were significantly reduced during glucose infusion at 250 and 175 mg/dl (p less than 0.05), but not at 140 and 120 mg/dl. We conclude that hyperglycemia inhibits the occurrence of the MMC in the stomach and suppresses plasma motilin levels. The differential sensitivity of motility and motilin concentration to different degrees of hyperglycemia suggests that hyperglycemia can inhibit antral motility independent of plasma motilin. In contrast, the duodenal MMC appears to be insensitive to hyperglycemia. This suggests that the antral and duodenal MMCs are mediated by different mechanisms. Our observations indicate the importance of serum glucose in regulating gastric motility.     

Effect of systemic gastric acid stimulation and intragastric pH changes on synchronous antral gastrin and somatostatin release in anesthetized,nonatropinized duodenal ulcer patients and controls

The synchronous changes in antral gastrin and somatostatin release in anesthetized, nonatropinized duodenal ulcer patients and control subjects were investigated by serial intraoperative blood sampling from the right gastroepiploic vein. The mean basal antral plasma gastrin and somatostatin concentrations of the two groups did not differ significantly. The significantly greater gastric acid secretory response to systemic gastric acid stimulation (pentagastrin stimulation) in duodenal ulcer patients compared with that of control subjects was not linked to any difference in antral somatostatin release pattern. The decrease in antral plasma gastrin release was significantly lower after acid instillation and the increase was significantly higher after alkali instillation in duodenal ulcer patients compared with those of controls, indicating an abnormal gastrin response to intragastric pH changes in duodenal ulcer patients, which was again not found to be coupled to any significant difference in antral somatostatin release. The results suggest that an abnormal somatostatin-mediated inhibition of gastrin release and/or gastric acid secretion does not exist in duodenal ulcer patients.     

Fasting and postprandial gastrointestinal motility in ulcer and non-ulcer dyspepsia.

This study aimed to compare fasting and postprandial gastrointestinal motor patterns in patients with ulcer and non-ulcer dyspepsia. Forty five subjects were studied: 10 with uncomplicated gastric ulcer, eight with uncomplicated duodenal ulcer, 18 with chronic idiopathic dyspepsia, and nine healthy asymptomatic controls. Gastrointestinal fasting and postprandial motor patterns were recorded using a low compliance perfusion technique. The interdigestive antral cumulative motility index, computed for 30 minutes before the appearance of duodenal activity fronts, and the number of activity fronts with an antral component were significantly less in patients with ulcers and those with non-ulcer dyspepsia compared with asymptomatic controls. The patient groups also had a reduced antral motor response to a solid-liquid test meal compared with healthy controls. Intestinal motor abnormalities (bursts of non-propagated phasic pressure activity and discrete clustered contractions) were recorded in a minority of patients, all with associated irritable bowel symptoms. In conclusion, antral hypomotility is a frequent but nonspecific motor abnormality in dyspepsia; abnormal motor patterns of the small bowel are less frequent and seem to be confined to patients with concomitant irritable bowel syndrome.     

Interdigestive motor activity in patients with systemic sclerosis

Fasting antral, duodenal, and jejunal motor activity and plasma motilin and pancreatic polypeptide were studied in 14 patients with systemic sclerosis, 6 and 9 without clinical evidence of small bowel involvement, and 8 healthy control subjects. Normal interdigestive motor activity was present in control subjects and patients without intestinal involvement. However, cyclic motor activity was absent in 3 of the patients with intestinal disease and the motility index per interdigestive cycle (or per 6-h recording period in those without cyclic activity) was significantly less in the antrum (181 +/- 103 mm2 compared with 760 +/- 86 and 1116 +/- 96 mm2 for patients without involvement and healthy control subjects, respectively), duodenum (153 +/- 101 mm2 compared with 1425 +2- 186 nd 1055 +/- 241 mm2), and jejunum (268 +/- 131 mm2 compared with 1166 +/- 97 and 1105 +/- 128 mm2). Metoclopramide and bethanechol significantly increased motor activity at the three sites in all subjects but the magnitude of the metoclopramide response was less in patients with intestinal involvement. Fasting concentrations of motilin and pancreatic polypeptide exhibited cyclic variation with peak values occurring during phase 3 of the interdigestive cycle. Plasma motilin during each phase of motor activity was significantly higher in patients with scleroderma, with or without intestinal involvement, than in control subjects. The abnormal motor activity demonstrated here indicates a possible mechanism by which intestinal stasis and bacterial overgrowth could occur and by which clinical disturbances of intestinal transit might arise.     

Gastroduodenal motility in chronic dyspepsia. 2. Postprandial motility

After ingestion of a solid test meal the postprandial motor activity in 17 dyspeptic patients and 12 healthy controls were examined. In all individuals the gastric emptying was measured by scintigraphy. - The antral pressure activity after food intake was delayed in dyspepsia and showed a distinct reduction with time (antral hypomotility). In contrast the postprandial duodenal motility was increased significantly (duodenal hyperdyskinesia). All 6 dyspeptic patients with prolonged gastric emptying had gastroduodenal manometric abnormalities. - Our results suggest that in chronic dyspepsia the interdigestive and postprandial motility is often disturbed. The delayed gastric emptying occurs because of impaired antral peristalsis and/or increase of duodenal resistance.     

Effects of smoking on interdigestive gastrointestinal motility

The effect of smoking on interdigestive gastrointestinal motility is little studied but may play a role in gastrointestinal morbidity. We studied gastroduodenal motility in 10 volunteers (five smokers and five nonsmokers) using a water-perfused pressure catheter. A pH probe was placed in the duodenal bulb. Baseline motility was recorded until phase III of the migrating motor complex had occurred in the stomach three times in order to record two complete cycles of MMC activity. Subjects then began smoking until phase III activity occurred again (mean duration of smoking 117 min). During the control period, all subjects had normal MMC cycles and there were no differences between smokers and nonsmokers. While smoking, no gastric phase III was observed in any subject and gastric motility was markedly reduced. In seven of 10 subjects, smoking did not prevent the occurrence of normal duodenal phase III activity. Three subjects had no duodenal phase III activity during smoking. The duodenal pH profile did not change during smoking and motilin levels continued to fluctuate in conjunction with phase III activity. In conclusion, smoking abolished phase III activity in the stomach without affecting the plasma motilin cyclic fluctuations or duodenal bulb pH. In contrast, smoking has little effect on duodenal motility.