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Gastrointestinal motility after pancreatoduodenectomy.

Pancreatoduodenectomy (PD) is a major surgical procedure which is accompanied by a high morbidity of between 30 and 50%. A large part of this morbidity is caused by delayed gastric emptying (DGE), which is reported to have an incidence of between 30 and 40% and is associated with prolonged hospital stay. Several pathophysiological mechanisms are thought to cause this complication. Peroperative trauma of the pylorus and the occurrence of intra-abdominal abscesses play a role. Neuronal changes and disruption of the gastrointestinal (GI) intramural nervous plexus may be especially important regarding the pivotal role of the duodenum in the initiation and coordination of antroduodenal motor activity. Another important factor is the postoperative administration of enteral nutrition. Recently, it was demonstrated that cyclic enteral nutrition through a catheter jejunostomy led to a faster return to normal diet and shorter hospital stay than patients on continuous enteral nutrition; this might be partly caused by continuously elevated cholecystokinin levels. The effect of prokinetic agents has not been studied extensively, but a beneficial action on the return of postoperative gastric function after gastrointestinal surgery seems limited.

Animals↗

Adrenergic mechanisms in the control of gastrointestinal motility: from basic science to clinical applications.

Over the years, a vast literature has accumulated on the adrenergic mechanisms controlling gut motility, blood flow, and mucosal transport. The present review is intended as a survey of key information on the relevance of adrenergic mechanisms modulating gut motility and will provide an outline of our knowledge on the distribution and functional role of adrenoceptor subtypes mediating motor responses. alpha1-Adrenoceptors are located postsynaptically on smooth muscle cells and, to a lesser extent, on intrinsic neurons; alpha2-adrenoceptors may be present both pre- and postsynaptically, with presynaptic auto- and hetero-receptors playing an important role in the modulation of neurotransmitter release; beta-adrenoceptors are found mainly on smooth muscle cells. From a clinical standpoint, adrenoceptor agonists/antagonists have been investigated as potential motility inhibiting (antidiarrheal/antispasmodic) or prokinetic agents, although at present their field of application is limited to select patient groups.

Adrenergic Agents↗

Gastrointestinal motility and gastric pH and emptying following ingestion of diazepam.

The effects of diazepam on antroduodenal motility, gastric pH and gastric emptying rate were investigated in 10 volunteers. Gastric emptying was assessed using paracetamol absorption and antroduodenal motility and pH by means of a perfused multilumen tube. On the first study day, the volunteers received paracetamol in phase I after the occurrence of one complete interdigestive motility complex (IDMC). Diazepam was given on the second study day at the beginning of the first phase I and paracetamol was given one IDMC later. The rate of absorption correlated with motility (P less than 0.03). Some volunteers were fast absorbers on the first study day and slow on the second, indicating that absorption rate is not constant, but dependent on gastroduodenal motility. Diazepam tended to increase the gastric emptying rate and enhanced the amplitude of contractions and the motility index during phase II (P less than 0.02). Gastric pH increased after ingestion of diazepam (P less than 0.05).

Adult↗

A hitherto unknown pattern of pathologic gastrointestinal motility--a cause of repeated vomiting?

We report the case of a 20-year-old woman with functional vomiting who presented with symptoms of anorexia nervosa. Antroduodenal and upper jejunal perfusion manometry was performed using an eight-lumen catheter. The investigation revealed a hitherto unknown motility pattern consisting of continuous simultaneous contractions at high frequency from the antrum down to the upper jejunum. The observation suggests that this disorder was related to the patients symptomatology.

Adult↗

Pilot study of the efficacy of renzapride on gastrointestinal motility and symptoms in patients with constipation-predominant irritable bowel syndrome.

AIM: To investigate the efficacy and safety of renzapride, a potent 5-hydroxytryptamine type-4 receptor full agonist and 5-hydroxytryptamine type-3 receptor antagonist in patients with constipation-predominant irritable bowel syndrome. METHODS: In this dose-escalating pilot study, 17 patients with constipation-predominant irritable bowel syndrome received placebo, renzapride 2 mg o.d. and renzapride 2 mg b.d. sequentially for 28 days. Response was determined by radio-opaque marker measurement of overall gastrointestinal and segmental colonic transit and patients' assessment of their irritable bowel syndrome symptoms. RESULTS: Renzapride reduced mean overall gastrointestinal transit time (placebo, 2.9 +/- 1.6 days; renzapride 2 mg o.d., 2.6 +/- 1.4 days; renzapride 2 mg b.d., 1.9 +/- 1.6 days) (P = 0.024) and accelerated segmental colonic transit, with statistically significant differences for renzapride 2 mg b.d. over placebo in caecum/ascending colon (P = 0.019) and descending colon (P = 0.022). Renzapride also reduced abdominal pain, increased the number of pain-free days and improved stool consistency. The frequency of reported adverse events was similar on renzapride and placebo. CONCLUSIONS: Renzapride is well-tolerated, stimulates gastrointestinal transit and improves symptoms in patients with constipation-predominant irritable bowel syndrome, particularly at the 2 mg b.d. dose, where improvements in gastrointestinal symptoms were evident over placebo. This study has established proof of concept and supports further investigation of renzapride in patients with constipation-predominant irritable bowel syndrome.

Adult↗

A long-term porcine model for measurement of gastrointestinal motility.

Animal models have become an essential tool in the investigations of gut motility under experimental conditions. To determine the influence of various anaesthetic drugs on the motility pattern of the gastroduodenal tract, a new long-term model has had to be developed for allowing measurements in conscious and unrestrained as well as in sedated and analgosedated pigs. Since mechanical ventilation influences gut motility, it was necessary that this animal model enabled the investigation of the effect of drugs causing sedation and analgosedation during spontaneous breathing. Seven male, castrated pigs, German landrace, 32-40 kg bodyweight (BW) were investigated in this study. After habituation of the pigs to local housing conditions over 5 days, the animals were trained over 4 days to prepare for experimental situations and investigators. Pigs were inserted with a central venous catheter and with percutaneous enterogastrostomy (PEG) under general anaesthesia. Intestinal motility was measured by intraluminal impedancometry. The catheter was introduced over the PEG into the stomach and positioned into the duodenum by duodenoscopy. Measurements were done in conscious, unrestrained pigs and with sedated, and analgosedated animals on subsequent days. The habituation and training of the pigs to the investigators and for the laboratory conditions took between 7 and 9 days. The initial anaesthesia protocol for the instrumentation using remifentanil/propofol led to pyloric spasm and was thus unsuitable for duodenal intubation with an endoscope. In contrast, a combination of ketamine/propofol enabled this procedure. It was practicable to measure gut motility in conscious, unrestrained pigs. Spontaneous breathing was sufficient under propofol sedation and analgosedation using fentanyl-propofol. Systematically local application of polividon iodine in the area of the subcutaneous catheters avoided the necessity of using systemic prophylactic antibiotics. In conclusion, the habituation and training for 9 days enabled the measurement of gut motility by intraluminal impedancometry in conscious pigs. The insertion of the catheter was done during general anaesthesia using a combination of propofol and ketamine. For the future determination of gut motility performed under general anaesthesia, each sedation and analgosedation concept has to be evaluated to see whether it allows spontaneous breathing or whether mechanical ventilation is necessary.

Animals↗

Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouse.

Serotonin-selective reuptake transporter (SERT) expression is decreased in animal models of intestinal inflammation and in individuals with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS), and it is possible that resultant changes in intestinal serotonin signalling contribute to the manifestation of clinical features associated with these disorders. The objective of this investigation was to determine whether inhibition of SERT function leads to changes in gut motility and sensitivity. Mice underwent a 14-day treatment with the SERT inhibitor, paroxetine (20 mg kg(-1)), or vehicle (saline/propylene glycol). Gastrointestinal (GI) transit following charcoal gavage, colonic motility, stool frequency and visceromotor responses to colorectal distension were evaluated. In mice treated with paroxetine, stool output was decreased, upper GI transit was delayed, and colonic sensitivity to a nociceptive stimulus was attenuated. These results demonstrate that reduced SERT function (via pharmacological blockade) significantly alters GI motility and sensitivity in mice, and support the concept that altered SERT expression and function could contribute to symptoms associated with IBS and IBD.

Animals↗

Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation.

1. We have studied the effect of cannabinoid agonists (CP 55,940 and cannabinol) on intestinal motility in a model of intestinal inflammation (induced by oral croton oil in mice) and measured cannabinoid receptor expression, endocannabinoids (anandamide and 2-arachidonylglycerol) and anandamide amidohydrolase activity both in physiological and pathophysiological states. 2. CP 55,940 (0.03 - 10 nmol mouse(-1)) and cannabinol (10 - 3000 nmol mouse(-1)) were more active in delaying intestinal motility in croton oil-treated mice than in control mice. These inhibitory effects were counteracted by the selective cannabinoid CB(1) receptor antagonist SR141716A (16 nmol mouse(-1)). SR141716A (1 - 300 nmol mouse(-1)), administered alone, increased intestinal motility to the same extent in both control and croton oil-treated mice. 3. Croton oil-induced intestinal inflammation was associated with an increased expression of CB(1) receptor, an unprecedented example of up-regulation of cannabinoid receptors during inflammation. 4. High levels of anandamide and 2-arachidonylglycerol were detected in the small intestine, although no differences were observed between control and croton oil-treated mice; by contrast anandamide amidohydrolase activity increased 2 fold in the inflamed small intestine. 5. It is concluded that inflammation of the gut increases the potency of cannabinoid agonists possibly by 'up-regulating' CB(1) receptor expression; in addition, endocannabinoids, whose turnover is increased in inflamed gut, might tonically inhibit intestinal motility.

Analgesics↗

Motilin effects on gastrointestinal motility and lower esophageal sphincter (LES) pressure in dogs.

Natural porcine motilin induces phasic contractions of the lower esophageal sphincter in dogs. These contractions are related to gastric contractions, which have the characteristics of interdigestive-motility patterns. Duodenal alkalinization produces an insignificant LES pressure increase after 5 minutes. No effect of motilin was observed when using isolated canine muscle strips.

Animals↗

Primary structures and effects on gastrointestinal motility of tachykinins from the rainbow trout.

Purification and structural characterization of tachykinins from rainbow trout (Oncorhynchus mykiss) intestine has demonstrated the presence of three different peptides related to the mammalian tachykinins: substance P, neurokinin A, and neuropeptide-gamma. The substance P- and the neurokinin A-related peptides present in the intestine are identical to the tachykinins previously isolated from the trout brain. The neuropeptide-gamma-related peptide (Ser-Ser-Ala-Asn-Pro-Gln-Ile-Thr-Arg-Lys-Arg-His-Lys-Ile-Asn-Ser-Phe- Val-Gly-Leu-Met-NH2), not previously identified in brain tissue, has the sequence of the neurokinin A-related tachykinin at its COOH-terminus. Both trout substance P and neurokinin A stimulated the motility of isolated trout intestinal muscle [pD2(-log of EC50) values 8.5 +/- 0.15 and 7.35 +/- 0.08, respectively] and the vascularly perfused trout stomach (pD2 values 9.63 +/- 0.23 and 8.18 +/- 0.23, respectively). Trout substance P was 14 times more potent than trout neurokinin A in the intestine and 28 times more potent in the stomach. The data suggest that receptors interacting with tachykinins in the trout gastrointestinal tract have a similar selectivity as the mammalian NK-1 receptor.

Amino Acid Sequence↗

Effects of intracerebroventricular administration of neurotensin, substance P and calcitonin on gastrointestinal motility in normal and vagotomized rats.

The effects of intracerebroventricular (ICV) vs. intravenous (IV) injection of neurotensin, substance P and calcitonin on intestinal myoelectrical activity were examined in fed rats. ICV administered neurotensin and calcitonin restored the 'fasted' pattern of intestinal activity, i.e. the migrating myoelectric complex (MMC) at a dose as low as 12 and 0.2 pmol, respectively, whereas substance P only reduced significantly (P less than 0.01) the duration of the postprandial pattern when injected ICV (48 pmol). Administered systemically at doses 100 times higher than the smallest active doses by the ICV route, calcitonin induced a fasted pattern, while neurotensin and substance P did not modify the fed pattern. The effects of ICV administration of neurotensin and calcitonin were abolished after vagotomy but the shortening effect of substance P on the duration of the postprandial pattern was still present. It is concluded that these three neuropeptides act centrally to control the pattern of intestinal motility in fed rats by shortening the 'fed' pattern for substance P and by restoring the MMC pattern for calcitonin and neurotensin, this last effect being mediated by the vagus.

Animals↗

Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome.

BACKGROUND: Corticotropin-releasing hormone (CRH) plays a key role in modulating intestinal motility in stressed animals. AIMS: To evaluate the effect of CRH on intestinal motility in humans and to determine whether patients with irritable bowel syndrome (IBS) have an exaggerated response to CRH. SUBJECTS: Ten IBS patients diagnosed by Rome criteria and 10 healthy controls. METHODS: CRH (2 micrograms/kg) was intravenously administered during duodenal and colonic manometry and plasma adrenocorticotropic hormone (ACTH) was measured by radioimmunoassay. RESULTS: CRH induced motility of the descending colon in both groups (p < 0.001) and induced greater motility indexes in IBS patients than in controls (p < 0.05). CRH produced duodenal phase III motor activity in 80% of the subjects and duodenal dysmotility in 40% of IBS patients. Abdominal symptoms evoked by CRH in IBS patients lasted significantly longer than those in controls (p < 0.05). CRH induced significant increases in plasma ACTH levels in both groups (p < 0.001) and produced significantly higher plasma ACTH levels in IBS patients than in controls (p < 0.001). CONCLUSION: Human intestinal motility is probably modulated by exogenous CRH. The brain-gut in IBS patients may have an exaggerated response to CRH.

Adrenocorticotropic Hormone↗

Gastrointestinal motility problems in the elderly patient.

Statistics abound demonstrating the aging of the population, and this comes as no news to physicians caring for an increasing number of elderly patients. This group experiences the expected age-related physiologic declines, including systems critical to integrative functions such as immunologic, neurologic, and metabolic systems. Although an increased prevalence of several common gastrointestinal disorders occurs in the elderly person, aging per se appears to have less direct effect on most gastrointestinal functions, in large part because of the functional reserve of the gastrointestinal tract. Although irritable bowel symptoms decrease with aging, there seems to be an increase in many gastrointestinal disorders of function and motility. The gastroenterologist will frequently encounter elderly patients with complaints of dysphagia, anorexia, dyspepsia, and disorders of colonic function. Understanding age-related changes in gastrointestinal physiology and effects of common comorbid illnesses enhances the ability to evaluate and treat these common, troublesome symptoms.

Aged↗

Effect of some i.v. anaesthetic agents on canine gastrointestinal motility.

Thiopentone 20 mg kg-1, ketamine 8 mg kg-1 and minaxolone 2 mg kg-1 were administered to fasting greyhound dogs. Mechanical and electrical activities from stomach, duodenum, jejunum and ileum were recorded using strain gauge force transducers and implanted bipolar electrodes. Thiopentone and minaxolone caused intense activity in the duodenum and jejunum (phase I and phase II of the interdigestive cycle), but not the stomach or ileum. The activity following injection of thiopentone or minaxolone was prevented by premedication with either atropine 0.05 mg kg-1 or pentolinium 0.2 mg kg-1. Ketamine had no influence on gastrointestinal activity or the response to thiopentone or minaxolone. None of these drugs altered the basal electrical rhythm of the intestine.

Action Potentials↗

Cardiopulmonary and gastrointestinal motility effects of xylazine/ketamine-induced anesthesia in horses previously treated with glycopyrrolate.

OBJECTIVE: To assess the usefulness of glycopyrrolate (GLY) in preventing the decrease in cardiac index (CI) usually caused by xylazine (XYL)/ketamine (KET)-induced anesthesia in horses. ANIMALS: 6 healthy horses. PROCEDURE: Horses were treated with saline solution or 2.5 micrograms of GLY/kg of body weight, administered i.v. 15 minutes later, XYL (1 mg/kg) was administered i.v., followed 5 minutes later by KET (2 mg/kg) administration. The horses were positioned in left lateral recumbency, insufflated with 15 L of oxygen/min, and maintained for 30 minutes on the infusion of 0.05 mg of XYL and 0.1 mg of KET/kg/min. Mean, systolic, and diastolic arterial blood pressures, mean pulmonary arterial and central venous pressures, heart rate, CI, and arterial and mixed venous blood gas tensions were recorded up to 40 minutes after anesthesia induction. Intestinal motility was assessed by auscultation of 4 abdominal quadrants for 24 hours after induction. Data were analyzed by Wilcoxon's rank-sum test for nonparametric observations, and by ANOVA for repeated measures and Scheffé's test for continuous parametric variables. RESULTS: Horses given GLY had significantly higher heart rate; mean, systolic, and diastolic arterial blood pressures; CI; oxygen delivery; and mixed venous oxygen tensions, with significantly less tissue oxygen extraction, compared with saline-treated horses. Both groups had complete loss of intestinal motility associated with general anesthesia. CONCLUSIONS: GLY significantly reduced the cardiovascular dysfunction attributable to general anesthesia with XYL and KET. The return of intestinal motility was delayed by 3 to 6 hours without causing any serious side effects.

Acid-Base Equilibrium↗

Effect of cyclical unipolar depression on upper gastrointestinal motility and sleep.

Cyclic 48-h unipolar depression is a rare form of recurrent affective disorder. We studied a single patient to determine (a) if there is an association between psychiatric status and migrating motor complex activity; and (b) if phase III of the migrating motor complex is in phase with rapid eye movement sleep in depression. There was marked reduction in phase III of the migrating motor complex during the depressed (n = 7) compared with the euthymic phase (n = 13), and a lack of coherence between phase III migrating motor complex activity and sleep stages in both depressed and nondepressed phases. The depressed state may be associated with altered upper gastrointestinal motor function.

Aged↗

The effects of medetomidine and xylazine on gastrointestinal motility and gastrin release in the dog.

The effect of medetomidine, a potent and highly selective alpha2-adrenoceptor agonist, on the motility of the gastric antrum, duodenum, mid-jejunum and ileum was investigated in ten dogs. Its effect on the release of gastrin was also determined. Administration of medetomidine intramuscularly (i.m.) at a dose of 40 microg/kg inhibited the motility of the gastric antrum, duodenum, mid-jejunum and ileum significantly, in comparison to administration of xylazine intramuscularly at a dose of 2.0 mg/kg. The release of gastrin was also significantly decreased in dogs receiving medetomidine. It was found to inhibit the motility in the gastric antrum and duodenum longer than in the mid-jejunum and ileum, presumably by acting specifically on alpha2-adrenoceptors, likely at the peripheral level. Medetomidine also inhibited the gastric contraction associated with gastrin secretion.

Adrenergic alpha-Agonists↗