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Duodenal motility in fasting dogs: humoral and neural pathways mediating the colonic brake.

We have previously described a negative feedback loop that inhibits duodenal motility when nutrients are infused into the ileum and colon. In the present study, we examined the role of extrinsic innervation and plasma levels of peptide YY (PYY) in mediating this phenomenon. We perfused neurally intact (n = 5 dogs) or extrinsically denervated (n = 6 dogs) isolated loops of proximal colon with isomolar NaCl or a mixed-nutrient solution at 2 and 6 ml/min for 4 h during fasting or for 2 h beginning 15 min after a meal. Both rates of infusion with NaCl prolonged the cycle length of the duodenal migrating motor complex (MMC) in the group with neurally intact loops but not in the group with extrinsically denervated loops. Nutrient infusions increased the MMC cycle length in both groups. Integrated plasma concentrations of PYY were increased by nutrients but not by NaCl in both groups. These data suggest that increased volumes and unabsorbed nutrients in the proximal colon alter proximal small bowel motility. Volume-induced effects are mediated via extrinsic nerves, whereas nutrient-induced effects may be mediated by humoral factors, such as plasma PYY.

Animals↗

Motor activity and transit in the autonomically denervated jejunum.

The role of extrinsic (autonomic) innervation in postprandial contractile activity of the small intestine is unknown. Using a canine model, we investigated the effects of complete extrinsic denervation on the parameters of fasting and postprandial jejunal contractions and their relationship to intestinal transit. Individual contractions were recorded using strain gauge transducers. Spatial and temporal parameters of contractions were analyzed by computer methods. Bolus injection of 14C-polyethylene glycol was used to calculate intestinal transit rates. Statistical comparisons of control and denervated animals were made by nonparametric tests. Extrinsic denervation did not abolish fasting or fed motor activity, but the following effects were observed: (1) the frequency of migrating motor complexes (MMCs) increased; (2) the onset of fed motor activity was delayed, and the duration of fed activity was shortened; (3) frequency, mean amplitude, and mean area of postprandial contractions were decreased; (4) fewer contractions propagated distally, and mean propagation distance was shortened; and (5) intestinal transit was slower for solids, but not for liquids. In the small intestine, extrinsic nerves modulate motor activity, which is under primary control of the intrinsic (enteric) nervous system.

Animals↗

Pranlukast, a leukotriene receptor antagonist, prolongs the duration of the migrating motor complex in dogs.

Current information on the effects of leukotriene receptor antagonists on gastrointestinal motility and their mechanisms of gastrointestinal side effects are unknown. Our study aimed to answer the question whether the leukotriene inhibition induced by Pranlukast alters the normal gastrointestinal contraction patterns, and whether any motility abnormalities found explain the gastrointestinal side effects of these types of medications. Seven dogs were used after implanting force transducers in the body and antrum of the stomach, duodenum, and jejunum to monitor gastrointestinal motility. Pranlukast was given orally to each dog at the end of the migrating motor complex during fasting experiments and 30 min after a standard meal during the fed stage, with continuous monitoring. The migrating motor complex was significantly prolonged, especially during phase I of 208.5 +/- 15.4 min (P < 0.05) at 30 mg/kg and of 280.3 +/- 12.5 min (P < 0.05) at 60 mg/kg, compared with controls (93.5 +/- 5.5 min). A significant reduction in the postprandial motility index was also noticed at 60 mg/kg (445.20 +/- 31.30 g x min; P < 0.001) compared to controls (728.20 +/- 26.76 g x min). In conclusion, we are the first to demonstrate that Pranlukast produces a significant inhibitory effect on gastrointestinal motility, which could explain in part some of the side effects observed with these types of drugs.

Animals↗

Neural mechanisms underlying migrating motor complex formation in mouse isolated colon.

1. Little is known about the intrinsic enteric reflex pathways associated with migrating motor complex (MMC) formation. Acetylcholine (ACh) mediates the rapid component of the MMC, however a non-cholinergic component also exists. The present study investigated the possible role of endogenous tachykinins (TKs) in the formation of colonic MMCs and the relative roles of excitatory and inhibitory pathways. 2. MMCs were recorded from the circular muscle at four sites (proximal, proximal-mid, mid-distal and distal) along the mouse colon using force transducers. 3. The tachykinin (NK(1) and NK(2)) receptor antagonists SR-140 333 (250 nM) and SR-48 968 (250 nM) reduced the amplitude of MMCs at all recording sites, preferentially abolishing the long duration contraction. Residual MMCs were abolished by the subsequent addition of atropine (1 microM). 4. The neuronal nitric oxide synthase inhibitor, N(omega)nitro-L-arginine (L-NOARG, 100 microM), increased MMC amplitude in the distal region, whilst reducing the amplitude in the proximal region. In preparations where MMCs did not migrate to the distal colon, addition of L-NOARG resulted in the formation of MMCs. Subsequent addition of apamin (250 nM) or suramin (100 microM) further increased MMC amplitude in the distal region, whilst suramin increased MMC amplitude in the mid-distal region. Apamin but not suramin reduced MMC amplitude in the proximal region. Subsequent addition of SR-140 333 and SR-48 968 reduced MMC amplitude at all sites. Residual MMCs were abolished by atropine (1 microM). 5. In conclusion, TKs, ACh, nitric oxide (NO) and ATP are involved in the neural mechanisms underlying the formation of MMCs in the mouse colon. Tachykinins mediate the long duration component of the MMC via NK(1) and NK(2) receptors. Inhibitory pathways may be involved in determining whether MMCs are formed.

Acetylcholine↗

Relationship between interdigestive motility and secretion of immunoglobulin A in human proximal small intestine.

In 17 healthy volunteers, we studied the dynamics of secretory immunoglobulin A (SIgA) release in the proximal small intestine (distal duodenum and proximal jejunum), using a modified triple-lumen perfusion technique. Secretory data were related to the current phase of the migrating motor complex (MMC), as recorded by manometry. In both segments, luminal SIgA output changed cyclically, with peak outputs occurring at the end of the MMC cycle (late phase II). These MMC-related changes were due to two factors: cyclic inflow of SIgA from more proximal sites, and a cyclic release of SIgA from the test segment that correlated in time with an increase in epithelial fluid secretion. Cyclic intestinal SIgA release may thus be another secretory component of the MMC. The data are compatible with the hypothesis that motility and SIgA release are linked by motility-activated chloride secretion from the intestinal crypts.

Adult↗

A double-blind placebo-controlled trial of omeprazole on characteristics of the migrating motor complex in healthy volunteers.

The aim of the study was to investigate a possible effect of omeprazole on the characteristics of the migrating motor complex. The study was performed as a double-blind crossover study and the pressure recordings were performed after 3 days of treatment with placebo or omeprazole 40 mg o.m. The calculations were based on 5 h of recording in each subject and in both investigations. There were two characteristics in the omeprazole group which were significantly different from placebo. Firstly, duodenal phase III was more often accompanied by an antral phase III and secondly, the duration of duodenal phase III was increased. The results suggest that the rapid cleaning mechanism, represented by phase III activity, is more pronounced after omeprazole treatment, possibly arising from its antisecretory effect.

Adult↗

Upper gastrointestinal motor activity in patients with slow-transit constipation. Further evidence for an enteric neuropathy.

Recent evidence indicates that patients complaining of severe chronic idiopathic constipation may have motor abnormalities not limited to the colon. We studied by manometric means gastric and small bowel motility in a homogeneous group of patients with chronic idiopathic constipation, ie, the slow transit type. Twenty-one patients were recruited for the study and compared to 33 healthy subjects. Manometric examination was carried out for about 5 hr fasting and 1 hr after a standard meal. Analysis of the manometric tracings revealed during fasting no abnormalities in number and configuration of migrating motor complex with respect to controls. However, in 70% of patients motor abnormalities were detected, represented by bursts of nonpropagated contractions and discrete clustered contractions. After feeding, the patient group displayed a significantly shorter antral motor response to the meal with respect to controls; moreover, intestinal bursts of nonpropagated contractions were found in 19% of patients, and 14% of them had an early return of the activity fronts. We conclude that patients with slow transit constipation frequently display motor abnormalities of the upper gut. These findings further strengthen the concept that this condition may represent a panenteric disorder.

Adult↗

HIDA-cholescintigraphy in normals. Value of interrupting the migrating motor-complex (MMC).

The value of interrupting the migrating motor-complex (MMC) and computer-assisted technique in HIDA cholescintigraphy was studied in 10 healthy subjects. Sequential scintigrams were sufficient for evaluating biliary-bowel transit time, visualization of the gall bladder and liver wash-out. However, the point of dynamic equilibrium between net uptake and emptying of the tracer of the gall bladder and hepatic areas, required computer assisted technique. Finally, interruption of the MMC resulted in biliary-bowel transit within one hour in all, but only gall bladder visualization in 8, whereas in the fasting state the gall bladder was visualized in all, but with prolonged biliary-bowel transit in one subject.

Adult↗

Effects of long-term intravenous and intragastric L-arginine intervention on jejunal motility and visceral nitric oxide production in the hyperdynamic compensated endotoxaemic pig.

Alterations in L-arginine availability and nitric oxide (NO) synthesis in the intestinal muscularis may contribute to disturbed small intestinal motility that is observed during endotoxaemia. The aim of this study was to evaluate the effect of L-arginine infusion on visceral NO production and jejunal motility in hyperdynamic compensated endotoxaemic pigs. Fasted and saline-resuscitated pigs were intravenously infused for 24 h with endotoxin (lipopolysaccharide, 50 ng kg(-1) min(-1)) or saline (n = 6). Endotoxaemic pigs received either intravenous L-arginine (n = 6, 5.3 micromol kg(-1) min(-1)) or L-alanine (isocaloric, n = 6). After 24 h, intravenous L-arginine or L-alanine infusion was continued intragastrically for 32-h in an enteral meal. During (0-24 h) and 1 day postendotoxaemia (48-56 h), jejunal motility was recorded by manometry and analysed for migrating motor complex (MMC) characteristics. Visceral NO production was measured at 24 and 48 h by 15N2-arginine-to-15N-citrulline conversion. Visceral NO production was increased during endotoxaemia and was higher in L-arginine than in L-alanine-treated pigs. One day postendotoxaemia, visceral NO synthesis was still increased in L-arginine but not in L-alanine-treated animals. Endotoxaemia shortened the MMC cycle duration and accelerated the MMC propagation velocity. Both were restored by L-arginine. Similar motility disturbances were observed one day postendotoxaemia and were also compensated by L-arginine infusion.

Alanine↗

Canine small bowel motor patterns and contractions are not neurally regulated during enteric nutrient infusion.

The aims of this study were to determine the effects of duodenal and jejunoileal nutrient infusions on small intestinal motor patterns and intestinal contractions in neurally intact and neurally isolated small bowel. Fifteen dogs were prepared with duodenal and jejunal infusion and manometry catheters and a diverting jejunal cannula. Ten of the dogs underwent in situ neural isolation of the jejunoileum. A mixed nutrient meal (0.5 kcal/ml) was infused into the duodenum or jejunum at 3 ml/min for 5 h. Control experiments involved infusion of a balanced salt solution. Manometric data collected on-line to a microcomputer were analyzed for direction, distance, and velocity of spread of single pressure waves (SPW) and clustered contractions. Isolated duodenal and jejunoileal nutrient infusions inhibited the fasting motor pattern in neurally intact and neurally isolated small bowel. Motor activity (motility index) increased slightly during nutrient infusion within groups, but there were few differences between groups. Neither neural isolation nor nutrient infusion had a consistent effect on spread of SPW or migration of clustered contractions. Isolated duodenal and jejunoileal nutrient infusions in the dog inhibit fasting motor patterns and increase motor activity slightly but have little effect on characteristics of individual and clustered contractions. Extrinsic innervation to the jejunoileum or intrinsic neural continuity of the jejunum with the duodenum had little effect on single or grouped contractions. Although the changes in motor activity demonstrated in this study appear small, alterations in intestinal transit and absorption may still occur and may be of importance physiologically.

Animals↗

Interdigestive gastroduodenal motility in patients with ulcer-like dyspepsia: effect of ranitidine.

Interdigestive gastroduodenal motility was studied manometrically in 16 patients with ulcer-like dyspepsia due to hypersecretory gastroduodenitis (group A) and in a control group of 6 healthy subjects (group B). After a basal recording period sufficient to record at least two activity fronts (AF) of the migrating motor complex (MMC) of the gastroduodenal tract, we administered 100 mg of ranitidine intravenously to 8 patients of group A (group A1), and the same dose of ranitidine to the remaining 8 patients of group A (group A2) after pretreatment with cimetidine 200 mg i.v. to block the acid secretion. The interdigestive motility of patients with hypersecretory gastroduodenitis is characterized by a decrease in frequency and duration of the activity fronts of MMC, which may play a role in the pathogenesis of mucosal lesions. Ranitidine induced premature and prolonged activity fronts in all patients without antisecretory pretreatment, and in the majority of patients in whom the acid secretion was previously blocked.

Duodenitis↗

Patterns of intestinal motility recovery during the early stage following abdominal surgery: clinical and manometric study.

The purpose of this study was to evaluate the pattern of recovery of intestinal motility using manometric and clinical assessment in the postoperative ileus following abdominal surgery. We reviewed the charts of 18 patients who underwent partial colectomy for colon cancer (group A, without vagotomy) and compared them to those of 15 patients who underwent gastrectomy with truncal vagotomy and reconstruction by the Billroth I technique (group B, with vagotomy). A three-lumen catheter was inserted via the nose into the proximal jejunum for drainage of intestinal fluids and to record intestinal motility at laparotomy. The first appearance of a burst activity following a silent period and a migrating motor complex (MMC) was at 3.8 hours (mean) and 16.4 hours, respectively, in group A, and at 2.5 and 14.3 hours, respectively, in group B. The first audible bowel sounds and the time of feeling abdominal fullness and passage of flatus was at 34.8, 47.5, and 62.9 hours (group A), and at 43.0, 53.8, and 77.9 hours (group B), respectively. The peak volume of nasointestinal drainage was recorded at 16 to 24 hours in group A and 40 to 48 hours in group B (p < 0.05). As measured by manometric examination, an MMC reappeared within a few hours after surgery. Physiologic postoperative ileus was ended when MMCs extended throughout the gastrointestinal (GI) tract with forwarding GI fluids.

Colectomy↗

Gastric secretion in cystic fibrosis in relation to the migrating motor complex.

BACKGROUND: Patients with cystic fibrosis (CF) have been claimed to have defect intestinal motility and gastric acid secretion. The aim of this work was to study the interdigestive motility and the motility-related secretions in the upper gastrointestinal tract in patients with CF compared to healthy controls. METHODS: Concomitant gastroduodenal manometry combined with intragastric perfusion was performed in 12 healthy volunteers and 10 patients with CF. RESULTS: Eight CF patients showed a normal migrating motor complex. Motility-related gastric secretion of acid and bicarbonate was evaluated in six patients and did not differ from healthy subjects. Gastric net fluid secretion was significantly decreased in the CF patients and bilirubin reflux was significantly increased. The CF patients with pancreatic insufficiency lacked motility-related variations in plasma levels of motilin and pancreatic peptide. CONCLUSIONS: No defect in fasting motility or gastric secretion of acid or bicarbonate could be seen in well-nourished adult CF patients. The main finding was a significantly lower net fluid secretion and higher bilirubin reflux compared to healthy subjects. Indications of a genetic relationship could be seen.

Adult↗

Innervation of pylorus in control of motility and gastric emptying.

The motility index (MI) and contractile frequency were determined for the gastric antrum, pylorus, and duodenum during digestive and interdigestive states in eight dogs before and after resection of the ramus pyloricus nervi vagi (NR) and after selective proximal vagotomy (SPV) subsequent to NR. Neither NR nor subsequent SPV altered the migrating motor complex in the interdigestive state. In the digestive state, NR decreased the MI in the antrum, pylorus, and duodenum. The MI did not further change after SPV subsequent to NR. The cholecystokinin antagonist L364,718 decreased MI in the antrum, pylorus, and duodenum. After NR, L364,718 caused a further reduction in the MI during administration. Gastric emptying was accelerated after NR. SPV subsequent to NR increased gastric emptying further. L364,718, in the absence of NR, accelerated gastric emptying but only during the initial period of emptying. After NR, L364,718 also decreased the time required for emptying of 50 and 100% of the meal. After SPV subsequent to NR, no additional acceleration of emptying occurred.

Animals↗

Neural control of small intestinal giant migrating contractions.

We investigated the neural mechanisms of control of giant migrating contractions (GMCs) in five conscious dogs. After control recordings, a Thiry-Vella loop was prepared from the middle segment, and the remaining two segments were reanastomosed. GMCs were stimulated by intravenous administration of fentanyl and erythromycin lactobionate, oral administration of loperamide and erythromycin stearate, and gastric or intraluminal administration of cider vinegar in the loop. In the intact state, the agents stimulated GMCs in all three segments, and they propagated uninterruptedly from the point of their origin to the terminal ileum. The propagation velocity of GMCs increased, whereas that of migrating motor complexes (MMCs) decreased distally. After Thiry-Vella loop formation, the agents stimulated GMCs independently in the three segments, and they propagated only to the end of the segment in which they started. In the intact small intestine, the GMCs produced ascending and descending inhibition of spontaneous phase II contractions but did not interrupt the caudad propagation of the ongoing MMC. After Thiry-Vella loop formation, the ascending inhibition was unaltered, but the descending inhibition occurred only in the segment containing the GMC. We conclude that the propagation of GMCs in the small intestine is controlled by the enteric nerves. The extrinsic nerves control the ascending inhibition produced by GMCs, whereas the enteric nerves control the descending inhibition.

Animals↗

Entrainment of duodenal activity to periodic feeding.

The electrical activity of the antrum and proximal duodenum was recorded simultaneously with bar pressing for food in various feeding conditions. During restricted feeding (RF; food available from 1200 to 1600 hr; lights-on from 0800 to 2000 h), large-amplitude slow potentials of duodenal origin were observed 3-5 hr preceding food access. These potentials occurred in short trains at irregular intervals of approximately 1 min and appeared to be associated with the active phase of the migrating motility complex. At least 8-10 days on RF were required before these irregular contractions (ICs) reliably preceded food access. The distribution of ICs showed a circadian variation during food deprivation, and transients lasting 4-6 days were observed in response to 6- or 8-hr phase delays of food access. These observations suggest that ICs are modulated by a circadian mechanism. On the average, the increase in ICs occurred about 2 hr earlier than bar pressing in anticipation of food, and there was no specific relation between individual ICs and bar pressing. However, bar pressing frequently occurred 0.5 min or longer after an increase in electromyogram (EMG) amplitude. Unreinforced bar pressing was never observed during a quiescent EMG.

Animals↗

Stimulation of beta-adrenoceptors with isoprenaline inhibits small intestinal activity fronts and induces a postprandial-like motility pattern in humans.

AIMS: To investigate the effects of beta-adrenoceptor stimulation, using the agonist isoprenaline and the antagonist propranolol, on migrating motor complexes in the upper intestine of 16 healthy human volunteers. METHODS: Fasting motility was monitored using a tube with water perfused side holes connected to a pneumohydraulic system. Continuous eight hour recordings were obtained from each volunteer after a 12 hour fasting period. In all experiments, saline was given as control for the first four hour period and beta-adrenergic agents for the next four hours. In separate control studies, saline was given for the whole eight hour period. RESULTS: Isoprenaline (2.5 micrograms/kg/min) reduced the number of activity fronts (phase III) of migrating motor complexes from 3 (2-4) in controls to 1 (0-2) during isoprenaline infusion (p < 0.01). Also, phase II-like activity replaced the regular motility pattern (p < 0.01). By contrast, propranolol (25 micrograms/kg/min) did not induce any significant changes in phase III compared with controls. Saline alone had no effect on motor activity. CONCLUSIONS: Isoprenaline inhibited activity fronts in the human proximal small intestine and induced a postprandial-like motility pattern, whereas propranolol did not affect motor patterns. Stimulation of beta-adrenoceptors is of importance in the control of motor activity of the human small intestine, especially under stressful conditions with high adrenergic activity.

Adrenergic beta-Agonists↗

Response of migrating motor complex to variation of fasting intraluminal content.

The characteristics of the phases of the migrating motor complex (MMC) were studied in the antrum, duodenum, and jejunum after alteration of intraluminal gas and acaloric fluid in 17 healthy volunteers. Aspiration of gas and fluid from the upper gastrointestinal tract reduced motor activity. In the antrum and duodenum, phase II contraction amplitude decreased, while in the duodenum and jejunum, the duration of phase II decreased and phase I increased. Phase III contraction frequency decreased in the duodenum only. Intragastric instillation of gas caused an increase of phase II duration and contraction amplitude in all regions. Similar effects were observed after intragastric instillation of fluid. Fasting periodic motor activity is responsive to volume changes of intraluminal gas and acaloric liquid content.

Adult↗