Motility In Healthy Volunteers Research Articles

Randomized Placebo-Controlled Double-Blind Crossover Trial of Buspirone in Functional Dysphagia and Ineffective Esophageal Motility

Introduction: Functional Dysphagia (FD) is a syndrome in which patients report dysphagia without evidence of Gastroesophageal Reflux Disease (GERD) or a histopathology-based esophageal motility disorder. There are data that argue that Ineffective Esophageal Motility (IEM) is the manometric correlate of FD. IEM is defined as a High Resolution Esophageal Manometry (HREM) with 50% or more of the swallows having a Distal Contractile Index (DCI) of. Methods: We performed a prospective, double-blind, placebo-controlled, cross-over trial of 10 patients with both FD and IEM. Patients were randomized to one of two groups for a period of six total weeks. Group A patients were treated with buspirone for two weeks followed by a two-week washout period and subsequently treated with placebo. Patients in Group B were treated with placebo for the first two weeks and buspirone the last two weeks. Outcomes measured at baseline, end of week 2, and week 6 include the Mayo Dysphagia Questionnaire-14 (MDQ-14), the GERD-HRQL, and HREM. A sample size of 10 patients was found to have 80% power to detect a difference of 25% in the number of failed or weak swallows. Results: The mean age of our 10 patients was 53 +/- 9 years and 70% were female. While 70% of the patients treated with placebo had IEM, only 50% of those treated with buspirone had IEM. However, this difference was not statistically significant. Furthermore, when comparing those treated with placebo with those treated with buspirone, there was no statistically significant difference in resting lower esophageal sphincter pressure, median integrated residual pressure, mean DCI, or percentage of swallows weak, failed, or normal (Table 1). There was also no statistically significant difference in any of the questions in the MDQ-14 or the GERD-HRQL (Table and Figure 1). Of note, patients had a statistically significant decrease in the total GERD-HRQL total score when treated with placebo compared to baseline levels.Figure: Percentage of Patients with Dysphagia at Baseline, With Placebo, and After Buspirone.Table: Table. Buspirone versus Placebo in Functional Dysphagia and Ineffective Esophageal MotilityConclusion: Despite previous data showing improved motility in healthy volunteers, our study shows no difference in terms of HREM parameters or symptom scores in FD and IEM patients treated with buspirone compared to placebo. Further research is necessary to identify novel agents.

A randomized double‐blind placebo‐controlled crossover‐style trial of buspirone in functional dysphagia and ineffective esophageal motility

Studies suggest that Ineffective Esophageal Motility (IEM) is the manometric correlate of Functional Dysphagia (FD). Currently, there is no accepted therapy for either condition. Buspirone is a serotonin modulating medication and has been shown to augment esophageal peristaltic amplitude in healthy volunteers. We aimed to determine if buspirone improves manometric parameters and symptoms in patients with overlapping IEM/FD. We performed a prospective, double-blind, placebo-controlled, crossover-style trial of 10 patients with IEM/FD. The study consisted of two 2-week treatment arms with a 2-week washout period. Outcomes measured at baseline, end of week 2, and week 6 include high resolution esophageal manometry (HREM), the Mayo Dysphagia Questionnaire-14 (MDQ-14), and the GERD-HRQL. The mean age of our 10 patients was 53±9years and 70% were female. After treatment with buspirone, 30% of patients had normalization of IEM on manometry; however, there was 30% normalization in the placebo group as well. Comparing buspirone to placebo, there was no statistically significant difference in the HREM parameters measured. There was also no statistically significant difference in symptom outcomes for buspirone compared to placebo. Of note, patients had a statistically significant decrease in the total GERD-HRQL total score when treated with placebo compared to baseline levels. Despite previous data demonstrating improved esophageal motility in healthy volunteers, our study shows no difference in terms of HREM parameters or symptom scores in IEM/FD patients treated with buspirone compared to placebo. Further research is necessary to identify novel agents for this condition.

Pharyngeal swallowing and oesophageal motility during a solid meal test: a prospective study in healthy volunteers and patients with major motility disorders

The factors that determine how people eat when they are healthy or have disease have not been defined. We used high resolution manometry (HRM) to assess pharyngeal swallowing and oesophageal motility during ingestion of a solid test meal (STM) in healthy volunteers and patients with motility disorders. This study was based at University Hospital Zurich (Zürich, Switzerland). Healthy volunteers who responded to an advertisement completed HRM with ten single water swallows (SWS) in recumbent and upright positions followed by a 200 g rice STM in the upright position. Healthy volunteers were stratified for age and sex to ensure a representative population. For comparison, consecutive patients with major motility disorders on SWS and patients with dysphagia but no major motility disorders on SWS (disease controls) were selected from a database that was assembled prospectively; the rice meal data were analysed retrospectively. During STM, pharyngeal swallows were timed and oesophageal contractions were classified as representing normal motility or different types of abnormal motility in accordance with established metrics. Factors that could potentially be associated with eating speed were investigated, including age, sex, body-mass index, and presence of motility disorder. We compared diagnoses based on SWS findings, assessed with the Chicago Classification v3.0, with those based on STM findings, assessed with the Chicago Classification adapted for solids. These studies are registered with ClinicalTrials.gov, numbers NCT02407938 and NCT02397616. Between April 2, 2014, and May 13, 2015, 72 healthy volunteers were recruited and underwent HRM. Additionally, we analysed data from 54 consecutive patients with major motility disorders and 53 with dysphagia but no major motility disorders recruited between April 2, 2013, and Dec 18, 2014. We found important variations in oesophageal motility and eating speed during meal ingestion in healthy volunteers and patients. Increased time between swallows was accompanied by more effective oesophageal contractions (in healthy volunteers, 20/389 [5%] effective swallows at <4 s between swallows vs 586/900 [65%] effective swallows at >11 s between swallows, p<0·0001). Obstructive, spastic, or hypercontractile swallows were rare in healthy volunteers (total <1%). Patients with motility disorders ate slower than healthy volunteers (14·95 g [IQR 11-25] per min vs 32·9 g [25-40] per min, p<0·0001) and pathological oesophageal motility were reproduced when patients consumed the STM. In healthy volunteers, eating speed was associated only with frequency of swallows (slope 2·5 g per min per pharyngeal swallow per min [95% CI 1·1-4·0], p=0·0009), whereas in patients with dysphagia, it was correlated with frequency of effective oesophageal contractions (6·4 g per min per effective contraction per min [4·3-8·5], p<0·0001). Diagnostic agreement was good between the HRM with SWS and rice STM (intra-class correlation coefficient r=0·81, 95% CI 0·74-0·87, p<0·0001). Our results show normative values for pharyngeal swallowing and oesophageal motility in healthy volunteers. Detailed analysis of HRM data acquired during an STM shows that the rate-limiting factor for intake of solids in health is the frequency of pharyngeal swallowing and not oesophageal contractility. The reverse is true in patients with oesophageal motility disorders, in whom the frequency of effective oesophageal contractions determines eating speed. University Hospital Zurich.

Oesophageal manometry with a solid test meal: ready for prime time?

The decrement in quality of life to a patient with unexplained oesophageal symptoms cannot be overemphasised. A life lived with dysphagia or chest pain, without a specific diagnosis, can affect a patient on a daily basis (or even every meal). Evaluation usually begins with routine upper endoscopy. The addition of advanced imaging, a biopsy, or specialised brushing all too often fails to result in a conclusive diagnosis. Promising technologies to assess inflammation (ie, tissue impedance), 1 Ates F Yuksel ES Higginbotham T Mucosal impedance discriminates GERD from non-GERD conditions. Gastroenterology. 2015; 148: 334-343 Summary Full Text Full Text PDF PubMed Scopus (111) Google Scholar lower oesophageal sphincter distensibility, and motility (ie, endolumenal functional imaging probe) 2 Carlson DA Kahrilas PJ Lin Z et al. Evaluaiton of esophageal motility utilizing the functional lumenal imaging probe. Am J Gastroenterol. 2016; 111: 1726-1735 Crossref PubMed Scopus (137) Google Scholar are not ready for widespread use. The barium swallow is a lost art, providing variable information on motility, and is often performed without a solid bolus, limiting its usefulness. Diagnostic yield of high-resolution manometry with a solid test meal for clinically relevant, symptomatic oesophageal motility disorders: serial diagnostic studyThe diagnostic sensitivity of HRM for major motility disorders is increased with use of the STM compared with SWS, especially in patients with dysphagia. Observations made during STM can establish motility disorders as the cause of oesophageal symptoms. Full-Text PDF Pharyngeal swallowing and oesophageal motility during a solid meal test: a prospective study in healthy volunteers and patients with major motility disordersOur results show normative values for pharyngeal swallowing and oesophageal motility in healthy volunteers. Detailed analysis of HRM data acquired during an STM shows that the rate-limiting factor for intake of solids in health is the frequency of pharyngeal swallowing and not oesophageal contractility. The reverse is true in patients with oesophageal motility disorders, in whom the frequency of effective oesophageal contractions determines eating speed. Full-Text PDF

The influence of physical strain on esophageal motility in healthy volunteers studied with gas-perfusion manometry.

The influence of physical strain on the esophageal motility has already been examined in a number of studies. It was found that high physical strain compromises the sufficient contractility of the esophagus. However, it needs more examinations to verify these findings. To validate these results healthy volunteers were examined using gas-perfusion manometrie. Bicycle ergometry was performed to generate an exactly defined physical exercise. After a pilot study, the changing of the contraction amplitude was determined as the main variable to evaluate the esophageal motility, and the sample size was calculated. Eight subjects without esophageal diseases or symptoms were examined by simultaneous gas-perfusion esophageal manometry and bicycle ergometry. The results showed that high physical strain during bicycle ergometry can induce a significant decrease of the contraction amplitude (α = 5%, β = 10%). The 95% confidence interval of the quotient of contraction amplitude at rest and under physical strain is (1.074; 1.576). This effect is more pronounced in liquid acts of swallowing than in dry and is also more obvious at the middle measuring point (7.8 cm above the lower esophageal sphincter) than at the distal and proximal point (2.8 and 12.8 cm). Furthermore, a decreasing tendency of the contraction duration could be found. Gas-perfusion manometry is an inexpensive examination method, which enables the evaluation of the esophageal motility in moving test subjects under conditions of physical strain. It could be proved that physical strain negatively influences the esophageal motility by a decrease of the contraction amplitude.

Tu1126 Effects of Acotiamide on Esophageal Motility in Healthy Volunteers: a Randomized, Double-Blind, Placebo-Controlled, Crossover Study

shown that esomeprazole was effective in relieving nighttime HB and improving sleep quality and work productivity.1,2 Given that the regimen is likely to be available over-the-counter (with up to 14-day-use labeling) in 2014, results from subjects receiving esomeprazole 20 mg or placebo during the first 14 days are reported. Methods: Adults with a history of frequent nighttime HB and GERD-related sleep disturbances were eligible for inclusion; those with other conditions possibly contributing to sleep disturbance were excluded. Following a 7-day run-in period, subjects with moderate-to-severe nighttime HB and associated sleep disturbance on ≥3 of 7 days were randomly assigned to double-blind, once-daily treatment with esomeprazole or placebo. The current report includes data from the first 14 days for subjects receiving esomeprazole 20 mg or placebo. The occurrence of GERD-related sleep disturbance and the frequency/severity of HB episodes were recorded by subjects in a daily self-assessment diary. Efficacy outcomes included complete resolution of GERD-related sleep disturbance (no sleep disturbance on 7 consecutive days) and relief (no more than 2 nights with sleep disturbance in 7 consecutive days) and HB resolution (no HB on 7 consecutive days during the preceding week). The proportion of subjects with relief/resolution at weeks 1 and 2 of treatment was compared using a chi-square test. Survival analysis was performed on the days to first resolution of sleep disturbance (defined as first day patient responded no to sleep disturbance question). Results: The efficacy analysis set for study 1 and 2 included 441 and 262 subjects, respectively. Baseline demographics and clinical characteristics were well balanced between the treatment groups. Results for both studies (Table) demonstrated that a significantly higher proportion of subjects treated with esomeprazole 20 mg had relief/resolution of GERD-related sleep disturbances and resolution of nighttime, daytime, and 24-h HB in weeks 1 and 2 of treatment. Conclusion: In this population of subjects with a history of frequent nighttime HB and GERD-related sleep disturbances, a 14-day regimen of esomeprazole 20 mg once daily was significantly more effective than placebo in resolving HB symptoms and associated sleep disturbances, with improvements in sleep occurring as early as the first 2 nights in the majority of subjects. Ref: 1. Johnson DA, et al. Am J Gastroenterol. 2005;100:1914-22. 2. Johnson D, et al. Aliment Pharmacol Ther. 2010;32:182-90. Efficacy Outcomes With 14-Day Treatment With Esomeprazole 20 mg or Placebo

Normative data of high‐resolution impedance manometry in the Chinese population

Current normative data of high-resolution manometry have been obtained from Western populations, and esophageal motility disorders have been categorized using Chicago classification. However, the utility of high-resolution impedance manometry (HRiM) in the Chinese population has not been evaluated. The study aimed to investigate the normal reference of esophageal motility in healthy volunteers (as defined by Chicago classification) using HRiM. Healthy, fasted volunteers underwent HRiM in a supine position with 10 liquid swallows and 10 viscous swallows. Integrated relaxation pressure (IRP), distal contractile integral (DCI), contractile front velocity (CFV), and distal latency were calculated. The interquartile ranges and the 95th percentile range for each metric were obtained. Forty-two healthy volunteers were enrolled with 411 total liquid swallows and 398 viscous swallows available for analysis. A 20.5 mmHg of IRP and a 3195 mmHg·s·cm of DCI as the 95th percentile for liquid swallows were established. Using the reference range defined by Chicago classification, 6.3% (26/411) weak peristalsis and 0.7% (3/411) failed peristalsis for liquid swallows were observed; 12 (28.6%, 12/42) and 2 (4.7%, 2/42) individuals were diagnosed as esophagogastric junction outflow obstruction and weak peristalsis for liquid swallows. Compared with liquid swallows, viscous swallows had a decreased IRP (P = 0.000) and CFV (P = 0.000), and an unchanged DCI (P = 0.211). HRiM normative data of both liquid and viscous swallows from healthy Chinese volunteers were established. The IRP and CFV were significantly decreased in the viscous swallows compared with those of the liquid swallows.

Assessment of Small Bowel Motility in Patients With Chronic Intestinal Pseudo-Obstruction Using Cine-MRI

Chronic intestinal pseudo-obstruction (CIPO) is a rare, serious motility disorder, with life-threatening complications over time. However, lack of an established, non-invasive diagnostic method has caused delays in the diagnosis of this intractable disease. Cine-magnetic resonance imaging (MRI) is an emerging technique, with a potential to evaluate the motility of the entire bowel. We compared small bowel motility in healthy volunteers, patients with irritable bowel syndrome (IBS), and those with CIPO, using cine-MRI, and evaluated the usefulness of cine-MRI as a novel diagnostic method for CIPO. Twelve healthy volunteers, IBS patients, and CIPO patients prospectively underwent cine-MRI at 1.5 T. Luminal diameter, contraction ratio, and contraction cycle were measured and compared between the groups. Cine-MRI provided sufficient dynamic images to assess the motility of the entire small bowel. Luminal diameter (mean±s.d.) in CIPO patients was significantly higher than that in healthy volunteers and IBS patients (43.4±14.1, 11.1±1.5, and 10.9±1.9 mm, respectively), and contraction ratio was significantly lower in CIPO patients than that in healthy volunteers and IBS patients (17.1±11.0%, 73.0±9.3%, and 74.6±9.4%, respectively). No significant differences were observed in the contraction cycle. This study is the first to assess the clinical utility of cine-MRI in CIPO patients. Cine-MRI clearly detected contractility impairments in CIPO patients. Cine-MRI is noninvasive, radiation-free, and can directly evaluate the entire small bowel peristalsis, and can detect the affected loops at a glance; therefore, it might be extremely useful for the diagnosis and follow-up of CIPO patients in clinical practice.

Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers

There are limited data concerning the effects of 5-HT(1A) receptor activation on esophageal motility. Sumatriptan, a 5-HT(1A) receptor agonist, was recently reported to enhance esophageal peristalsis after intravenous administration. Buspirone, an orally available 5-HT(1A) receptor agonist, was shown to modulate gastroduodenal motor function. Our aim was to evaluate the effect of buspirone on esophageal motility of healthy volunteers. On two separate visits, 20 healthy volunteers aged 21-29 years (nine women) underwent esophageal manometry before and 10, 30, and 60 minutes after the administration of buspirone 20-mg or placebo capsule, according to a double-blind crossover design. At each time point, we compared buspirone and placebo effects on: resting pressure of the lower esophageal sphincter (LES); residual pressure and duration of LES relaxation; amplitude, duration, and onset velocity of esophageal body contractions, during 10 swallows of 5 mL of water. Significant analysis of variance differences (P < 0.05) are presented as mean ± standard deviation. Buspirone significantly increased mean distal esophageal wave amplitude (151 vs. 87 mmHg, P < 0.05) and duration (6.1 vs. 4.2 seconds, P < 0.05). Similarly, buspirone significantly increased mean LES resting pressure (26 vs. 21 mmHg, P < 0.05) and mean residual LES pressure (7.9 vs. 2 mmHg, P < 0.05), whereas reduced mean LES relaxation duration (7.2 vs. 8.0 seconds, P < 0.05) and mean distal onset velocity (7.6 vs. 14.7 cm/second, P < 0.05). Buspirone enhances esophageal peristalsis and LES function in healthy volunteers. Further study is warranted on the effects of buspirone on esophageal function and symptoms in patients with ineffective esophageal motility.

Efficacy of mosapride citrate in proximal gastric accommodation and gastrointestinal motility in healthy volunteers: a double-blind placebo-controlled ultrasonographic study

Mosapride citrate, a 5-hydroxytryptamine-4 receptor agonist, enhances antral contractions and gastric emptying, but its effects on proximal gastric accommodation and gastroduodenal motility have not been fully studied. The aim of the present study was to clarify the effects of mosapride citrate on proximal gastric accommodation and gastroduodenal motility in healthy volunteers, using ultrasonography. Fourteen healthy volunteers (mean age 25.3 years) were treated for 14 days with mosapride citrate (15 mg b.d.) or a placebo in a double-blind randomized fashion. Before and after drug treatment, ultrasonographic assessment of gastroduodenal motility was performed. For assessment of the gastric accommodation reflex, the cross-sectional area of the proximal stomach was measured after the incremental ingestion, with a straw, of up to 400 ml of a liquid meal (consommé soup: 13.1 kcal, 400 ml); this was done with the subject in a supine position. Gastric emptying, antral contractions, and the duodenogastric reflux were observed as described previously. In the subjects treated with mosapride citrate, the expansion rate of the cross-sectional area of the proximal stomach was significantly greater after the ingestion of 400 ml as compared to that of the subjects treated with the placebo. Similarly, gastric emptying and antral contractions increased significantly in the mosapride citrate group as compared to the placebo group. Although the duodenogastric reflux tended to decrease in the mosapride citrate group, it showed no significant difference between the two groups. This study shows that mosapride citrate enhances the meal-induced gastric accommodation reflex and promotes adequate gastroduodenal coordination and motility in healthy volunteers.

Duodenal hypersensitivity to acid in patients with functional dyspepsia-pathogenesis and evaluation

Functional dyspepsia (FD) is a subcategory of the functional gastrointestinal disorders according to the Rome III classification of functional gastroduodenal disorders. FD is characterized by the presence of symptoms that are believed to be associated with gastroduodenal lesions, particularly epigastric pain or burning, postprandial fullness, or early satiation, without the evidence of organic disease likely to explain the onset of these symptoms. Generally, multiple factors are considered to be involved in the onset of dyspeptic symptoms in patients with FD. Among these factors, acid is thought to be more important because proton pump inhibitors (PPIs) and histamine 2 (H2)-receptor antagonists have been proposed to be effective therapies for a subset of patients with FD. Although manometric methods, scintigraphic methods, electrogastrography and ultrasonography have been used to evaluate enterokinesis, a practical method for evaluating duodenal hypersensitivity to acid has not been reported. Recently, we attempted to evaluate duodenal hypersensitivity to acid and gastric motility by duodenal acidification using transnasal endoscopy. Using this method, we could simultaneously evaluate both dyspeptic symptoms and gastric motility in healthy volunteers. Furthermore, we evaluated duodenal hypersensitivity to acid in healthy volunteers and in patients with FD, and we reported that duodenal acidification induced dyspeptic symptoms more significantly in patients with FD than in healthy volunteers.

T1416 Influence of the 5-HT 1A Agonist Buspirone On Rectal Tone and On the Perception of Rectal Distension in IBS with Rectal Urgency

Background: β3-adrenoceptors (β3-AR) are expressed in adipocytes, heart, skeletal muscle, and smooth muscle. Agonists of β3-AR reduce the elevated tone and inhibit spontaneous contractions in the human isolated colon, but the exact site of action is not clear. β3-AR expression is co-localized with choline acetyl transferase (ChAT) in a majority of the neurons in human colonicmyenteric and submucosal plexus. Human selective β3-AR agonist, solabegron, inhibits cholinergic contractions and enhances release of somatostatin with no effect on carbachol-induced contractions in human isolated colon. A rodent selective β3-AR agonist inhibits castor oil-induced diarrhea in rats. Aim: To assess dose-related effects of solabegron on gastrointestinal and colonic transit in healthy human volunteers. Methods: In a randomized, double-blind study, 37 healthy male and female volunteers were randomized to placebo, 50 mg or 200 mg solabegron every 12 hours for 7 days. They underwent questionnaires to exclude gastrointestinal symptoms and significant multiple somatic symptoms, scintigraphic gastrointestinal and colonic transit using a validated technique, and bowel function (including stool frequency and consistency measured by Bristol stool form scale). The primary endpoints for analysis were gastric emptying at 2 hours and colonic geometric center (GC) at 24 hours. Analysis of covariance [(ANCOVA), adjusting for gender and body mass index (BMI)], was followed by two pairwise comparisons of each solabegron dose compared to placebo.Results: There was no overall or dose-related effect of solabegron on gastric, small bowel or colonic transit, or on stool frequency, form or ease of passage in healthy volunteers (table). Conclusion: While further studies in patients with motility disorders are awaited, it does not appear that the β3-AR agonist, solabegron, significantly alters gastrointestinal or colonic motility in healthy volunteers.

Proton pump inhibitors reduce gallbladder function

In the authors' previous study of gallbladder function before and after fundoplication, 58% of the patients demonstrated preoperative gallbladder motor dysfunction, and 86% of those retested after operation and cessation of proton pump inhibitors (PPIs) normalized. Because no study has directly assessed the impact of antisecretory agents on gallbladder function, this study measured gallbladder ejection fraction (GBEF) in healthy volunteers before and after initiation of PPIs. A total of 19 subjects completed the study, which included baseline determination of GBEF by cholecystokinin-stimulated hepatobiliary acid scan, 30 days of antisecretory therapy with omeprazole (40 mg daily), and repeat GBEF on day 30. Subjects were surveyed regarding compliance and symptoms. For 15 of 19 subjects, PPI therapy was associated with reduced gallbladder motility. Evolution of symptoms consistent with a biliary etiology was reported by 26.7% of these subjects. Short-term PPI therapy reduces gallbladder motility in healthy volunteers. Chronic PPI therapy may pose a risk for long-term gallbladder dysfunction and biliary complications.

Senna tea versus Erythromycin – two prokinetic agents for the assessment of large bowel motility in healthy volunteers using functional cine MRI

Introduction: The aim of our study was to develop a method to visualize and quantify large bowel motility using functional Cine MRI in comparing two different prokinetic agents.

Oral S(+)-Ketamine Does Not Change Visceral Perception in Health

Application of N-methyl-D-aspartate (NMDA)-receptor antagonists may hold promise for the treatment of visceral pain. In this study we evaluated the effect of oral S(+)-ketamine (sKET), a non-competitive NMDA-receptor antagonist, on visceral sensitivity in healthy volunteers. Eight healthy volunteers (five male, three female) underwent a gastric barostat study following oral administration of placebo, 25 mg sKET, and 50 mg sKET. Studies were performed in a double-blind randomized crossover fashion. Sensations evoked by stepwise isobaric distension (2 mm Hg/2 min) were scored on a 100-mm visual analogue scale. In addition, fasting and postprandial fundic volume were measured at a fixed pressure level (MDP + 2 mm Hg). During gastric distension, sKET did not alter sensation scores for bloating, nausea, satiation, and pain compared to placebo. sKET had also no effects on the thresholds for pain/discomfort, fundic wall compliance, fundic tone, or meal-induced fundic relaxation. sKET does not reduce visceral perception or gastric motility in healthy volunteers. The role of sKET in conditions characterized by visceral hypersensitivity needs to be studied further.

Effect of tegaserod, a 5-HT4 receptor partial agonist, on interdigestive and postprandial gastrointestinal motility in healthy volunteers

Effect of tegaserod, a 5-HT4 receptor partial agonist, on interdigestive and postprandial gastrointestinal motility in healthy volunteers

Effect of peppermint oil and caraway oil on gastrointestinal motility in healthy volunteers: a pharmacodynamic study using simultaneous determination of gastric and gall‐bladder emptying and orocaecal transit time

Although peppermint oil and caraway oil are frequently used in herbal drugs for abdominal discomfort and pain, the pharmacological insights into their effects on the gastrointestinal tract are poor. The pharmacodynamic effects of 90 mg peppermint oil (WS 1340) and 50 mg caraway oil (WS 1520) on the motility of the stomach and gall-bladder, and on the orocaecal transit time, in comparison with placebo, 10 mg cisapride and 10 mg n-butylscopolamine, were studied in 12 healthy volunteers. The study involved simultaneous ultrasonic determination of gastric and gall-bladder emptying, together with assessment of the orocaecal transit time using the lactulose H2 breath test. The combination of these methods allows three gastrointestinal organs to be studied in one subject simultaneously. The antral filling time was comparable with placebo, peppermint oil, caraway oil and cisapride, whereas it was significantly shortened (P = 0.04, two-sided paired t-test) with n-butylscopolamine. The gastric emptying time did not differ significantly between placebo, peppermint oil, caraway oil and cisapride, but was significantly prolonged by n-butylscopolamine (P = 0.04, two-sided paired t-test). Complete inhibition of gall-bladder emptying was caused by both oils and n-butylscopolamine. Cisapride significantly shortened gall-bladder emptying compared with placebo (P = 0.02, two-sided signed rank test). The orocaecal transit time was significantly prolonged by peppermint oil (P = 0.004) and n-butylscopolamine (P = 0.002), but not significantly prolonged by caraway oil (P = 0.06); it was significantly shortened by cisapride (P = 0.04, all two-sided paired t-test). Peppermint oil and caraway oil show a relaxing effect on the gall-bladder and the former slows small intestinal transit. Further studies should investigate the effects of both oils on a maximal contraction stimulus on the gall-bladder, and in patients suffering from motility disorders.

Role of endogenous nitric oxide in regulating antropyloroduodenal motility in humans

OBJECTIVES: Previously we demonstrated the involvement of nitric oxide (NO) in the regulation of interdigestive small intestinal motility in humans. The role of NO in postprandial motility remains to be studied. Therefore, we investigated the effect of the NO synthase inhibitor N G-monomethyl- l-arginine (L-NMMA) on antral, pyloric, and small intestinal postprandial motility in healthy volunteers. METHODS: Ten healthy male volunteers (ages 19–29 yr) underwent stationary antropyloroduodenal manometry recording during administration of a placebo or a high dose of L-NMMA (12 mg/kg within 5 min, followed by a maintenance infusion of 6.7 mg/kg/h i.v.) in a double blind, randomized order. Motility was recorded before and after ingestion of a 300-kcal liquid meal. RESULTS: Two and a half minutes (±0.4 min) after infusion of L-NMMA, rapidly propagated phase III-like activity was observed in the proximal duodenum in every subject. Mean propagation velocity was 26 ± 5 cm/min. The duration of the phase III-like activity increased proximally (9.2 ± 1.6 min) to distally (12 ± 1.5 min), whereas the frequencies of contractions were similar in all manometric channels (10.8 ± 0.3/min). Postprandial duodenal motility was disrupted by phase III-like activity in four of 10 subjects (15–58 min after the meal) during L-NMMA infusion, but not during placebo. Antral or pyloric motility and basal pyloric tone were not significantly altered by L-NMMA, relative to the placebo. CONCLUSIONS: We showed that inhibition of NO biosynthesis triggers the onset of a rapidly propagating phase III and shortens the postprandial period, indicating that NO is involved in the modulation of fasting and postprandial small intestinal motility in humans.

The effect of lactulose on tolerance of gastric feeding in long term ICU patients

Lactulose was reported to inhibit gastric tone and motility in healthy volunteers [1]. Double blind placebo controlled study using lactulose four times 15 ml daily (ie 40 g) or saline for prevention of ventilator associated pneumonia was performed in our ICU during 1999-2000. In this report the impact on gastric feeding tolerance of lactulose given into stomach is evaluated.

Effect of gastric distension and duodenal fat infusion on biliary sphincter of oddi motility in healthy volunteers

Although sphincter of Oddi (SO) dysfunction has been implicated in the pathogenesis of postcholecystectomy syndrome and pancreatitis, little is known about normal physiologic stimuli, such as intraduodenal fat on human SO motility. Furthermore, gastric distension that frequently accompanies endoscopic manometry has been shown in animal studies to affect SO motility. We evaluated the effects of intraduodenal fat and gastric distension on SO basal pressure. Asymptomatic volunteers had SO manometry performed while sequentially performing gastric distension and intraduodenal fat perfusion. Five subjects (ages 29.8 +/- 4.8 years, range 22-35 years) had a mean basal sphincter of Oddi pressure of 23.4 +/- 5 mm Hg (range 17-31 mm Hg). Injection of air into the stomach caused no appreciable change in either intragastric pressure or SO pressure. Intraduodenal fat infusion resulted in a decrease in mean SO basal pressure from 23.4 +/- 5.0 to 4.4 +/- 4.4 mm Hg (P = 0.004). These results demonstrate that gastric distension does not affect SO basal pressure and that intraduodenal fat infusion reduces SO basal pressure.