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Quantitative analysis of peristalsis in the guinea-pig small intestine using spatio-temporal maps.

1. Peristalsis was evoked in guinea-pig small intestine by slow fluid infusion and recorded onto video and digitized. Spatio-temporal maps of diameter and longitudinal movement were constructed and parameters of motion were calculated. 2. During the filling of the isolated segments of intestine, rhythmic local longitudinal movements were observed at several points along the preparation. These phasic longitudinal muscle contractions were associated with small but significant local increases in diameter and probably reflect a passive mechanical coupling by connective tissue in the gut wall. In addition, occasional synchronized longitudinal muscle contractions caused net shortening of the preparation and always preceded the onset of peristaltic emptying. 3. Peristaltic emptying was characterized by a contraction of the circular muscle which usually started at the oral end of the preparation, that propagated aborally, propelling the contents. However, in 19 % of trials, the first circular muscle contraction occurred in the aboral half of the preparation. 4. The propagation of peristalsis consisted of separate sequential circular muscle contractions several centimetres long, particularly in the oral half of the preparation, giving a 'step-like' appearance to the spatio-temporal map. The gut was transiently distended aboral to the propagating circular muscle contraction due to the propulsion of contents. 5. At each point in the preparation, the longitudinal muscle remained contracted during the propulsive part of the circular muscle contraction. Only when the circular muscle contraction became lumen occlusive did lengthening of the longitudinal muscle take place. 6. Spatio-temporal maps are a powerful tool to visualize and analyse the complexity of gastrointestinal motility patterns.

Animals↗

Glucagon-like peptide-1 analogue LY315902: effect on intestinal motility and release of insulin and somatostatin.

LY315902 is an analogue of GLP-1 that yields a reduced clearance and longer half-life. The aim of the study is to assess the effect of LY315902 on fasting gastrointestinal motility, somatostatin and insulin release. Sprague-Dawley rats were fitted with three bipolar electrodes, 15, 25 and 35 cm distal to the pylorus. The effect of LY315902 and GLP-1 on migrating myoelectric complex (MMC) cycle length, duration and propagating velocity of activity fronts was studied for 60 min in conscious animals. The effect of LY315902 and GLP-1 on fasting small bowel motility was dose-dependent and treatment with exendin (9-39)amide, a GLP-1 receptor antagonist, together with LY315902 and GLP-1 completely antagonised the inhibitory effect of LY315902 and GLP-1 on fasting small bowel motility. Pretreatment with the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine (L-NNA) partly blocked the action of both LY315902 and GLP-1. Plasma insulin concentrations were not different from controls during infusion of LY315902 or GLP-1, while somatostatin concentrations were significantly higher during LY315902 and GLP-1 compared to saline. LY315902 has a longer duration of inhibitory action on the MMC than GLP-1, albeit similar effects on plasma insulin and somatostatin concentrations. The effect of LY315902 on motor control is mediated through the GLP-1 receptor and seems partly dependent on the L-arginine/NO pathway.

Animals↗

Macrolides in roles beyond antibiotic therapy.

Erythromycin and other macrolides with a closely related structure are widely used antibiotics. Side-effects related to administration of such drugs are mostly gastrointestinal. The direct effect of erythromycin on gastrointestinal motility was studied; it was found to have a stimulatory effect proximally, on stomach and duodenal motility, with an apparent distal inhibition. Gastric emptying was accelerated by erythromycin via an antroduodenal coordination mechanism, an effect that has proved to be beneficial in surgical and medical conditions in which gastroparesis is a problem. Erythromycin is now used experimentally and clinically; it has been found to accelerate gastric as well as gallbladder emptying and to have an effect on the oesophagus. Analogues of erythromycin have been developed that have potent gastrointestinal activity but little or no antibacterial potential. Macrolides modulate the antibacterial action of neutrophils, with some action on the oxidative burst. Finally, two new macrolide immunosuppressants have been developed that compare favourably with traditional drugs.

Erythromycin↗

Enteral naloxone reduces gastric tube reflux and frequency of pneumonia in critical care patients during opioid analgesia.

OBJECTIVE: Opioid analgesia impairs gastrointestinal motility. Enteral administration of naloxone theoretically allows selective blocking of intestinal opioid receptors caused by extensive presystemic metabolism. Therefore, we studied the effect of enteral naloxone on the amount of gastric tube reflux, the frequency of pneumonia, and the time until first defecation in mechanically ventilated patients with fentanyl analgesia. DESIGN: Prospective, randomized, double-blinded study. SETTING: University hospital intensive care unit. PATIENTS: Eighty-four mechanically ventilated, fentanyl-treated patients without gastrointestinal surgery or diseases. INTERVENTIONS: Patients were assigned to receive 8 mg naloxone or placebo four times daily via a gastric tube during fentanyl administration. MEASUREMENTS AND MAIN RESULTS: Thirty-eight patients received naloxone and 43 placebo; three patients were excluded because of protocol violation. Median gastric tube reflux volume (54 vs. 129 mL, p =.03) and frequency of pneumonia (34% vs. 56%, p =.04) were significantly lower in the naloxone group. In both groups, time until first defecation, ventilation time, and length of intensive care unit stay did not differ. There was no difference in fentanyl requirements between the naloxone and the placebo group (7 vs. 6.5 microg/kg/hr, p =.15). CONCLUSIONS: Our results provide evidence that the administration of enteral opioid antagonists in ventilated patients with opioid analgesia might be a simple-and possibly preventive-treatment of increased gastric tube reflux and reduces frequency of pneumonia.

Administration, Oral↗

Upper gastrointestinal function and glycemic control in diabetes mellitus.

Recent evidence has highlighted the impact of glycemic control on the incidence and progression of diabetic micro- and macrovascular complications, and on cardiovascular risk in the non-diabetic population. Postprandial blood glucose concentrations make a major contribution to overall glycemic control, and are determined in part by upper gastrointestinal function. Conversely, poor glycemic control has an acute, reversible effect on gastrointestinal motility. Insights into the mechanisms by which the gut contributes to glycemia have given rise to a number of novel dietary and pharmacological strategies designed to lower postprandial blood glucose concentrations.

Blood Glucose↗

Characterization of macrophage-like cells in the external layers of human small and large intestine.

In the external layers of human small and large intestine macrophage-like cells were characterized by immunohistochemical, histochemical and electron-microscopical methods. Using immunohistochemistry and a number of monoclonal antibodies, the presence and distribution of phenotypic subpopulations of macrophages were evaluated. In all locations macrophage-like cells were identified with antibody EBM11, which recognizes CD68 antigen, C3bi which recognizes CD11b, and partly with an antibody which recognizes protein 150,95 (CD11c). Macrophage-like cells in the external muscle layer were HLA-DR-positive (expressing the MHC class-II antigen), in contrast to macrophage-like cells in the subserosa and submucosa. Macrophage-like cells in the external muscle layer were mostly acid phosphatase-negative, and at the electron-microscopic level they were found to have features of macrophages: primary lysosomes, coated vesicles and pits. However, very few secondary lysosomes were present. Birbeck granules were not observed. It is concluded that in the external muscle layer of human small and large intestine numerous macrophages of a special type are present. It is discussed whether this cell type plays a role in gastrointestinal motility and/or has an immunological function.

Acid Phosphatase↗

Dopamine in gastrointestinal disease.

Dopamine is an important enteric neuromodulator. Herein we review the data that support a role for dopaminergic involvement in experimental duodenal and gastric ulceration; gastric, pancreatic, and duodenal secretion; gastrointestinal motility; and gastric and intestinal submucosal blood flow regulation. There also is support for a role for dopamine and dopamimetic agents in the treatment of certain experimental gastrointestinal diseases because some highly selective dopamine agonists are gastroprotective when given either parenterally or centrally. Based upon these observations, we suggest that dopamine is a key element of the "brain-gut axis" and represents a potentially important target for pharmacotherapeutic exploitation.

Animals↗

Intraileal capsaicin inhibits gastrointestinal contractions via a neural reflex in conscious dogs.

BACKGROUND & AIMS: The aim of the present study was to determine the effect of intraileal administration of capsaicin on gastrointestinal motility. METHODS: Mongrel dogs equipped with strain gauge force transducers on the stomach, small intestine, and colon were used. We studied the effects of intraileal capsaicin on gastrointestinal contractions with or without pharmacologic antagonists. The effects of capsaicin administration into the lumen of innervated and extrinsically denervated ileal Thiry loops were also studied. RESULTS: Intraileal capsaicin dose dependently inhibited postprandial contractions at all sites and interdigestive contractions in the upper gastrointestinal tract. Intraileal capsaicin-induced inhibition of gastrointestinal contractions was partially reversed by a nitric oxide (NO) synthase inhibitor, a 5 hydroxytryptamine-3 receptor antagonist (5-HT(3)), and an opiate antagonist. Administration of capsaicin into the innervated ileal Thiry loop had inhibitory effects on gastrointestinal contractions, but gastrointesinal motor activity was not affected by capsaicin administered into the extrinsically denervated Thiry loop. CONCLUSIONS: Stimulation of ileal afferent fibers by capsaicin inhibits gastrointestinal contractions via an extrinsic neural reflex.

Animals↗

Mechanisms by which food intake elevates circulating levels of hyaluronan in humans.

OBJECTIVES: Plasma hyaluronan is a potentially useful clinical test, especially in liver disease. It rises after eating, but mechanisms by which this occurs are not known. The study aimed at defining the effect of different food and liquid intake on plasma hyaluronan and to address mechanisms. DESIGN: The effects on plasma hyaluronan of ingestion of high-fat and low-fat meals, glucose solution, and saline, and of intravenous metoclopramide and oral cisapride were defined in healthy fasted subjects by serial measurements over 5 h. Hyaluronan was measured by a radiometric assay. RESULTS: After test meals and glucose ingestion, plasma hyaluronan rose to 1.7-13 times the fasting levels in 11 healthy volunteers. Peak values were observed in most subjects 45-90 min after ingestion and reached levels in six subjects that might suggest the presence of hepatic fibrosis or cirrhosis. No change occurred after ingestion of 0.48 L iso-osmotic NaCl solution, equal in bulk to the glucose solution. Stimulation of gastrointestinal motility with metoclopramide had no effect but oral cisapride induced a pattern of elevated plasma hyaluronan which mimicked that induced by foodstuffs. CONCLUSIONS: Displacement of hyaluronan from gastrointestinal tissues prevails over the increased clearance expected from elevated portal blood flow. The heightened flux of tissue fluid necessary to displace tissue hyaluronan is best explained by vasodilatation in response to ingestion of nutrients, and subsequent increase in intestinal lymph flow, rather than by fluid absorption, together with gut contraction. The discriminating value of plasma hyaluronan in clinical practice may be greatly enhanced by sampling in fasted subjects at rest.

Administration, Oral↗

Duodenal nutrient exposure elicits nutrient-specific gut motility and vagal afferent signals in rat.

Volume and chemical characteristics of meals in the gut have been proposed to generate vagal afferent signals that mediate the negative feedback control of ingestion and gastric emptying. Furthermore, duodenal nutrients elicit changes in gastrointestinal motility that may stimulate mechanosensitive vagal afferents. The degree to which the activity of an individual vagal afferent fiber can be modified by moth mechanical and nutrient properties in the gut remains unclear. The present studies evaluated the relationships between distal antral and proximal duodenal load-sensitive vagal afferent activity and gastroduodenal motility in response to duodenal nutrient exposure in ketamine-xylazine-anesthetized rats. Duodenal carbohydrate (glucose) and amino acid (peptone) infusions (0.2 ml/min, 0.2-0.5 kcal/ml) stimulated concentration-dependent increases in 1) antroduodenal contractions and 2) antral and duodenal vagal afferent activity beyond those attributable to osmolarity alone. In addition, duodenal peptone was more effective than equicaloric glucose in eliciting this vagal activity. These data demonstrate that the proximal duodenum can discriminate its nutrient chemical contents and that gastroduodenal load-sensitive vagal afferents indirectly transduce nutrient chemical information.

Animals↗

A miniature transducer for recording intestinal motility in unrestrained chronic rats.

An extraluminal strain gage force transducer has been developed for recording gastrointestinal motility in small animals such as rats. Two commercial strain gages are bonded and wires attached to form half a Wheatstone bridge. The device is placed between silicone sheeting and prepared for implantation. As many as six implanted transducers can record simultaneously contractions and tone variations of circular or longitudinal gastrointestinal muscles. The transducers have been implanted in more than 20 rats, with some units lasting up to 4 mo. Furthermore, good relationships exist between intraluminal pressure waves registered by a small intraluminal balloon and gut contractions registered by the transducer. The transducers are a useful and accurate tool for rodent gut motility studies.

Animals↗

Effects of aspirin and prostaglandin E2 on interdigestive motility complex and duodenogastric reflux in man.

Both increased duodenogastric reflux and chronic aspirin ingestion are associated with the development of gastric ulcers in man. Animal studies suggest aspirin increases duodenogastric reflux. Prostaglandin E2 protects gastric mucosa from the effects of many injurious agents and inhibits gastric motility, but its effect on duodenogastric reflux is unknown. We have studied the effects of aspirin and a synthetic derivative of prostaglandin E2 on duodenogastric reflux during fasting in six normal subjects, while concomitantly monitoring gastrointestinal motility by means of a perfused catheter system. We found that duodenogastric reflux (as measured by bile salt output in gastric aspirates) increased significantly (P less than 0.05) following both the prostaglandin E2 derivative and aspirin. This increase occurred in phases II and III of the interdigestive motility complex. Both drugs were associated with a significant reduction (P less than 0.05) in frequency and amplitude of antral contraction during phase II. Both drugs also induced a significant disruption (P less than 0.01) of phase III, increasing the number of complexes without an antral and duodenal component. These effects of aspirin may be one of the factors predisposing to the gastric mucosal damage associated with aspirin. The prostaglandin E2 derivative protects gastric mucosa by mechanisms other than reducing duodenogastric reflux and ameliorating the motility disturbances caused by aspirin.

Adult↗

Mediators for fat-induced ileal brake are different between stomach and proximal small intestine in conscious dogs.

Our aim was to determine the mechanisms by which intraileal fat alters proximal gastrointestinal motility--the ileal brake. Five mongrel dogs with ileal Thiry-Vella fistulas were equipped with strain gauge force transducers on the upper gut to measure contractile activity. Ileal infusions of 115 mmol/L oleic acid and triglyceride were studied in dogs with extrinsically innervated and extrinsically denervated Thiry-Vella loops. Plasma concentrations of peptide YY and total glucagon-like immunoactivity were measured. Oleic acid but not triglyceride inhibited postprandial contractions in the gastric antrum in dogs with innervated and denervated Thiry-Vella loops. Postprandial duodenal and jejunal motility was inhibited by oleic acid regardless of extrinsic denervation to the loops (P <0.05), but triglyceride inhibited small intestinal motility only in dogs with innervated Thiry-Vella loops. Intraileal oleic acid but not triglyceride increased plasma concentrations of peptide YY and total glucagon-like immunoactivity in dogs with innervated and denervated Thiry-Vella loops. Intraileal oleic acid inhibits gastric and small intestinal motility possibly via increased plasma concentrations of peptide YY and enteroglucagon. Intact extrinsic innervation is necessary for intraileal triglyceride to inhibit small intestinal motility.

Animals↗

Pharmacological modification of gastric emptying: effects of propantheline and metoclopromide on paracetamol absorption.

The rate of paracetamol absorption depends on the rate of gastric emptying. Propantheline delayed gastric emptying and markedly slowed the absorption of paracetamol in six convalescent hospital patients. Conversely, the absorption of paracetamol in five healthy volunteers was accelerated by metoclopramide, a drug which stimulates gastric emptying. The total 24-hour urinary excretion of paracetamol was not influenced by propantheline or metoclopramide. Other similar absorption interactions probably occur since drugs are poorly absorbed from the stomach and many therapeutic agents influence gastrointestinal motility.

Acetaminophen↗

Ghrelin: a novel player in the gut-brain regulation of growth hormone and energy balance.

Ghrelin is a newly discovered peptide hormone produced by the stomach that displays potent growth hormone-releasing activity and a stimulatory effect on food intake and digestive function while reducing energy expenditure. The isolation of ghrelin has led to new insights into how this gastric hormone links the endocrine control of nutritional homeostasis with growth hormone secretion and gastrointestinal motility through gut-brain interactions.

Animals↗

Diameter and wall thickness recording of canine pylorus with implantable miniature ultrasonic transducers.

Outer diameter and thickness of the muscular wall of canine pylorus were measured simultaneously by determining the distance between pairs of implanted ultrasonic transducers, evaluating the sonic transit time with a digital sonometer. For the study of the motility in the gastroduodenal transit zone, the ultrasonically determined pyloric responses were compared with signals from conventional strain-gauge transducers sutured to the neighboring duodenum and gastric antrum. After stimulation of the gastrointestinal motility by an intravenous bolus injection of cholecystokinin octapeptide, pyloric contractions with a frequency of 5.2 min-1 could be recorded for some minutes; those contractions were independent of the more rapid antral and duodenal motility. Together with the observed tonic constriction of the pyloric ring, which could be inhibited by intravenous injection of adrenaline, an autonomous role of the gastroduodenal junction as a true sphincter is supported.

Animals↗

The effects of gamma-radiation on intestinal motor activity and faecal pellet expulsion in the guinea pig.

The effects of whole-body gamma-radiation (10 Gy) on intestinal motor activity was examined in the small and large intestine of the guinea pig 18 hr post irradiation. Neurally mediated relaxations of isolated gut bath preparations were generally unaffected. However, the contractile responses to direct smooth muscle stimulation with the cholinergic muscarinic agonist carbachol or ganglionic stimulation of intrinsic cholinergic motor neurones were significantly increased in the duodenum and colon but not the jejunum. This increased sensitivity to cholinergic stimulation was reflected in an increased contractility and a shift in the concentration-response curves for carbachol. The specificity of radiation actions for cholinergic mediated contractions was further supported by the observation that histamine-evoked contractions were unaffected. In a second series of experiments we examined the effects of gamma-radiation on the rate of pellet expulsion from freshly excised colons. Both colons from irradiated animals and nonirradiated colons exposed to carbachol showed significantly faster rates of pellet expulsion, indicative of increased propulsive motility. Pretreatment of animals with 0.5 mg/kg sc of the 5HT3 receptor antagonist Granisetron prevented the effect of radiation and reduced the pellet expulsion rate to below normal. These results indicate that gastrointestinal motility disturbances seen in organ-bath preparations of the intestine from rats exposed to whole-body gamma-radiation may be related to an increased sensitivity of the cholinergic muscarinic system.

Animals↗

Radiography and image-intensified fluoroscopy of barium passage through the gastrointestinal tract in six healthy Amazon parrots (Amazona aestiva).

Gastrointestinal contrast studies were performed in six clinically healthy blue-fronted Amazon parrots (Amazona aestiva) using radiography and image-intensified fluoroscopy. During examination, the birds were confined in a perspex cage. The quality of the lateral radiographs was adequate for assessment of the contrast medium-filled gastrointestinal tract. Thirty minutes after administration of 20 mL/kg of a 25% barium sulphate suspension directly in the crop, in all birds the ventriculus was totally outlined by barium. After 60 min, the small intestine was filled in five of six birds. After 180 min, the crop was empty in all birds. The barium-outlined ventriculus had differences in shape on radiographs of individual birds and also between birds. The colon and cloaca had further filling after 120 to 300 min. With image-intensified fluoroscopy, gastrointestinal motility was evaluated. Contractions of the crop were seen, and boluses of contrast medium passing through the esophagus toward the proventriculus were easily identified. Proventricular contractions were rarely noted, but ventriculus motility was present and clearly defined. The ventriculus had a mean of 3.7 contraction cycles/min. In the duodenum and small intestine, rapid antegrade and retrograde peristaltic movements in combination with segmental contractions were seen. In the colon, occasionally very slow peristaltic activity, mainly of segmental nature, was present. During the examinations, no defeacation was recorded. Confinement in a small perspex cage provides an adequate and handy radiological set-up for evaluation of gastrointestinal passage and motility in birds, minimizing the influences of stress and anesthesia.

Animals↗