Influence of tegaserod on proximal gastric tone and on the perception of gastric distention in functional dyspepsia

Background Abnormalities in gastric sensorimotor function (hypersensitivity to distention and impaired meal accommodation) have been implicated in the pathophysiology of functional dyspepsia (FD). To study the effect of the 5‐HT₄ agonist tegaserod on sensitivity to gastric distention and gastric accommodation in FD. Methods Thirty FD patients (7 males, mean age 42 ± 2 years) underwent a gastric barostat study on two separate occasions, 2 weeks apart, after 5 days of pretreatment with placebo or tegaserod 6 mg b.i.d. in a double‐blind randomized order. After introduction of the barostat bag, graded isobaric distentions (2 mmHg increments/2 min) were performed to determine gastric compliance and sensitivity to distention. Subsequently, the pressure level was set at intra‐abdominal pressure [minimal distending pressure (MDP)] + 2 mmHg for 90 min, with administration of a liquid meal (200 mL; 300 kcal) after 30 min. Key Results Tegaserod had no influence on MDP (7.9 ± 0.4 vs 7.4 ± 0.4 mmHg) or fasting gastric compliance (44 ± 10 vs 61 ± 6 mL mmHg^?1) and on fasting thresholds for first perception (3.6 ± 0.4 vs 4.2 ± 0.2 mmHg above MDP) or discomfort (9.9 ± 0.7 vs 10.5 ± 0.5 mmHg above MDP). Tegaserod did not alter intra‐balloon volumes before and after the meal [respectively 146 ± 14 vs 120 ± 11 and 297 ± 28 vs 283 ± 29 mL, not significant (NS)], or the amplitude of the meal‐induced gastric relaxation (151 ± 23 vs 162 ± 23 mL, NS). In the subgroup with normal gastric emptying (n = 22), tegaserod significantly enhanced meal‐induced accommodation (126 ± 23 vs 175 ± 29 mL, anova P < 0.001). Conclusions & Inferences Tegaserod does not alter gastric sensorimotor function in FD patients as a group. In the subgroup with normal gastric emptying, tegaserod 6 mg b.i.d enhanced gastric accommodation.     

Assessment of gastric sensorimotor function in paediatric patients with unexplained dyspeptic symptoms and poor weight gain

Recent studies indicate that impaired meal accommodation or hypersensitivity to distention are highly prevalent in adult functional dyspepsia (FD). Our aim was to investigate whether similar abnormalities also occur in paediatric FD. Sixteen FD patients (15 girls, 10-16 years) were studied. The severity (0-3; 0, absent; 3, severe) of eight dyspeptic symptoms (epigastric pain, fullness, bloating, early satiety, nausea, vomiting, belching and epigastric burning) and the amount of weight loss were determined by questionnaire. All children underwent a gastric barostat study after an overnight fast to determine sensitivity to distention and meal-induced accommodation, which were compared with normal values in young adults (18-22 years). On a separate day, all patients underwent a gastric emptying breath test. A mean weight loss of 4.8 +/- 0.9 kg was present in 14 children. Compared with controls, patients had lower discomfort thresholds to gastric distention (8.8 +/- 1.0 mmHg vs 13.9 +/- 1.9 mmHg, P < 0.02) and gastric accommodation (87 +/- 25 mL vs 154 +/- 20 mL P < 0.04). Hypersensitivity to distention and impaired accommodation were present in respectively nine (56%) and 11 (69%) patients. No relationship was found between barostat and gastric emptying, which was delayed in only three patients. The majority of children with unexplained epigastric symptoms have abnormalities of gastric sensorimotor function.     

Elicitation of transient lower oesophageal sphincter relaxations in response to gastric distension and meal ingestion

The aim of this study was to compare the effect of graded gastric barostat distension and meal-induced fundic relaxation on the elicitation of transient lower oesophageal sphincter relaxation (TLOSR). In 15 healthy subjects, stepwise fundic distension and oesophageal manometry were performed simultaneously. Next, the effect of meal ingestion on proximal stomach volume and lower oesophageal sphincter function was studied. During stepwise barostat distension of the proximal stomach, a significant linear correlation between intragastric pressure (r = 0.91; P < 0.01) and the TLOSR rate during inflation and subsequent deflation (r = 0.96; P < 0.01) was found. A similar relationship was found for volume. In addition, after meal ingestion, the TLOSR rate increased significantly from 1.40 +/- 3 to 5.4 +/- 1.5 h-1 (P < 0.01) and 5.2 +/- 1.7 h-1 (P < 0.01), respectively, during the first and second 30-min postprandially. However, at similar calculated intragastric volumes, barostat distension led to a significantly higher TLOSR rate than the meal. Similarly, distension-induced increase in gastric wall tension, estimated from the measured bag pressure and volume using Laplace's law, was associated with significantly higher TLOSR rates (P < 0.01). In conclusion, the rate of TLOSRs in healthy volunteers is directly related to the degree of proximal gastric distension and pressure-controlled barostat distension is a more potent trigger of TLOSRs than a meal. The latter finding suggests that tension receptor activation is an important stimulus for TLOSRs.     

Characterization of gastric volume responses and liquid emptying in functional dyspepsia and health by MRI or barostat and simultaneous 13C-acetate breath test

Abstract The assessment of gastric accommodation and emptying by different methodologies provides inconsistent results. We aimed to compare magnetic resonance imaging (MRI), barostat and ¹³C‐acetate breath test (BT) for the assessment of gastric volume responses and emptying in healthy controls (HC) and patients with functional dyspepsia (FD). Eight HC and eight FD patients underwent: (i) continuous BT with simultaneous MRI in the upright position after ingestion of isocaloric, 300 kcal, 200 and 800 mL meals, both labelled with 100 mg of ¹³C‐acetate; and (ii) BT with gastric barostat after ingestion of the 200 mL meal. MRI measured total gastric volume and gastric content volume (GCV) at baseline, after filling and during emptying. Meal emptying half‐times (T½) for MRI and BT were calculated (mean ± SD). We found: (i) Initial GCV was lower in FD than in HC (762 ± 22 vs 810 ± 52 mL, P < 0.04) after the 800 mL meal but not the 200 mL meal. T½_MRI was shorter for the 800 mL than the 200 mL meal (P < 0.001), but similar in HC and FD (200 mL: HC 117 ± 30 min vs FD 138 ± 42 min, ns; 800 mL: HC 71 ± 16 min vs FD 78 ± 27 min, ns). In contrast, T½_BT was similar between meals and groups (200 mL: HC 111 ± 11 min vs FD 116 ± 19 min; 800 mL: HC 114 ± 14 min vs FD: 113 ± 17 min). (ii) Barostat measurements showed similar postprandial volume increases between groups. We conclude that direct measurements by MRI provide a sensitive, non‐invasive assessment of gastric accommodation and emptying after a meal. In contrast to MRI, BT did not detect faster emptying of high‐volume compared to low‐volume liquid nutrient meals in HC or FD.     

Effects and mechanisms of long-pulse gastric electrical stimulation on canine gastric tone and accommodation

Gastric electrical stimulation (GES) has been applied to treat gastroparesis and morbid obesity. The aims of this study were to evaluate the sites of stimulation and the mechanisms of GES on gastric tone and accommodation. Gastric tone and accommodation were evaluated with a barostat in surgically prepared dogs. GES was applied at seven different locations, and gastric tone was assessed at each site. The effect of truncal vagotomy on gastric tone and accommodation and the role of the nitrergic pathway were also evaluated. We have found: 1) GES induced varying degrees of gastric relaxation at all tested locations in normal dogs; 2) Gastric volume was also significantly increased with GES in vagotomized dogs and the change tended to be lower than that of normal animals; 3) Gastric accommodation was reduced during GES in both the normal and vagotomized dogs and the reduction tended to be more in the vagotomized animals; 4) The GES-induced increase in gastric volume was partially abolished by intravenous nitric oxide synthase inhibitor. GES at various sites of the stomach exerts inhibitory effect on gastric tone; the most effective sites are in the antrum along the lesser or greater curvature; the inhibitory effect of GES on gastric tone is partially mediated by the vagal and nitrergic pathway.     

Influence of the 5‐HT3 receptor antagonist ondansetron on gastric sensorimotor function and nutrient tolerance in healthy volunteers

Background Serotonin is believed to be involved in the regulation of the gastric accommodation reflex in man however which receptor subtype(s) are involved remains to be elucidated. Methods Eleven healthy subjects (nine men, age 19–30) underwent a gastric barostat and a drinking test after treatment with either placebo or ondansetron (8 mg intravenously). During the barostat protocol an intragastric flaccid bag was stepwise distended (2 mmHg increments 2 min) to determine gastric compliance and sensitivity to distention. Subsequently, the pressure level was set at intra‐abdominal pressure +2 mmHg while volume was followed before and after administration of a liquid meal (200 mL; 300 kcal). During the drink test volunteers drank at a rate of 15 mL min^?1 until maximal satiation. Results (mean ± SEM) were compared using t‐tests and mixed model analysis. Key Results Gastric compliance was not significantly altered by ondansetron (51.5 ± 5.6 vs 49.2 ± 5.2 mL mmHg^?1), neither were the pressure thresholds for first perception or discomfort. Ondansetron treatment did not affect basal gastric tone (173 ± 14 vs 156 ± 12 mL), neither did it affect the amplitude of the meal‐induced relaxation (160 ± 52 vs 131 ± 43 mL) or the maximum volume increase after the meal (264 ± 54 mL vs 234 ± 51 mL). During the drinking test the amount of liquid meal ingested at maximum satiation was significantly increased by ondansetron (784 ± 74 vs 907 ± 64 mL, P < 0.05). Conclusions & Inferences These data suggest that 5‐HT acting at 5‐HT₃ receptors is not involved in the control of gastric sensorimotor function, but contributes to the regulation of hunger and satiation in man.     

Mechanisms of symptomatic improvement after gastric electrical stimulation in gastroparetic patients

Abstract The aims were to investigate the effects of gastric electrical stimulation (GES) on autonomic function, gastric distention and tone, and central control mechanisms in gastroparetic patients. Ten gastroparetic patients refractory to standard medical therapy participated in this study and data were collected at baseline, within two weeks before surgery for implantation of GES system, and at follow‐up sessions between 6 and 12 weeks after GES therapy was initiated. In each session, electrocardiogram, electrogastrogram (EGG) and gastric barostat measurements were conducted before and after a caloric liquid meal. Positron Emission Tomography (PET) brain scans were performed on a separate day. During GES therapy there was a significant increase in the discomfort threshold for mean pressure from 21 mmHg at baseline to 25 mmHg at follow‐up, and for mean volume from 561 mL to 713 mL. A significant increase in the postprandial EGG power (amplitude) was observed between baseline and follow up. The sympathovagal balance was significantly decreased after GES therapy, indicating a significant increase in vagal activity. The cumulative PET data showed an increase in quantitative radioactive counts relative to the standardized data base in both the thalamic and caudate nuclei after chronic GES therapy. We conclude that our data suggest that the symptomatic improvement achieved by GES in gastroparesis is best explained by activation of vagal afferent pathways to influence CNS control mechanisms for nausea and vomiting accompanied by enhanced vagal efferent autonomic function and decreased gastric sensitivity to volume distention which enhances postprandial gastric accommodation.     

An experimental model for the study of transient lower oesophageal sphincter relaxation and motor function of the proximal stomach in humans

A simple and reliable experimental model would be useful in human research on new drugs which target transient lower oesophageal sphincter (LOS) relaxation. The aim was to investigate the effect of repeated distensions on the rate of transient LOS relaxation, LOS pressure and motor function of the proximal stomach. Twelve healthy subjects were studied with a multilumen manometric assembly incorporating a sleeve sensor for the LOS and a bag positioned in the proximal stomach and connected to a barostat. Intrabag volume was set at 75% of the threshold for gastric discomfort and maintained for two 30-min distension periods separated by a 45-min washout with the bag deflated. The studies lasted 145 +/- 2 min. The rate of transient LOS relaxations was similar during the two distensions, 3.5;2-4 vs 3;2.5-4 (median;interquartile range) and so was LOS pressure. Baseline intrabag pressure, as a measure of gastric tone, and the number of pressure waves, as a measure of phasic contractions, were also similar, 11.3;9.3-12.3 mmHg vs 10.8;9.3-12.5 mmHg and 16;13-28 mmHg vs 19;15-29 mmHg, respectively. Our model allows to perform 1-day studies which can assess two experimental conditions on transient LOS relaxations and motor function of the proximal stomach within an acceptable time span.     

Influence of abuse history on gastric sensorimotor function in functional dyspepsia

Abstract  Patients with functional gastrointestinal disorders have elevated rates of sexual or physical abuse, which may be associated with altered rectal sensorimotor function in irritable bowel syndrome. The aim was to study the association between abuse history and gastric sensorimotor function in functional dyspepsia (FD). We studied gastric sensorimotor function with barostat (sensitivity, compliance and accommodation) and gastric emptying test in 233 consecutive FD patients from a tertiary care centre (162 women, mean age 41.6 ± 0.9). Patients filled out self-report questionnaires on history of sexual and physical abuse during childhood or adulthood. Eighty-four patients (out of 198, 42.4%) reported an overall history of abuse [sexual and physical in respectively 30.0% (60/200) and 20.3% (42/207)]. FD patients reporting general as well as severe childhood sexual abuse have significantly lower discomfort thresholds during gastric distension [respectively 10.5 ± 0.4 vs 7.5 ± 1.0 mmHg above minimal distending pressure (MDP), P  = 0.014 and 10.5 ± 0.4 vs 6.6 ± 1.2 mmHg above MDP, P  = 0.007]. The corresponding intra-balloon volume was also significantly lower (respectively 579 ± 21 vs 422 ± 59 mL, P  = 0.013 and 579 ± 19 vs 423 ± 79 mL, P  = 0.033). Gastric accommodation was significantly more pronounced in patients reporting rape during adulthood (91 ± 12 vs 130 ± 40 mL, P  = 0.016). Abuse history was not associated with differences in gastric emptying. A history of abuse is associated with alterations in gastric sensorimotor function in FD. Particularly sexual abuse, rather than physical abuse, may influence gastric sensitivity and motor function.     

Assessment of gastric volume changes with sonometry compared with barostat

AIM: The aim was to investigate the validity of sonometry on the assessment of gastric volumes in comparison with gastric barostat. METHOD: Six dogs were implanted with gastric serosal electrodes, sonometric sensors, and a gastric cannula. Experiments were performed to assess sensor distance when an intragastric balloon was inflated with different volumes, after a meal with or without a balloon, and with gastric electrical stimulation. RESULTS: (i) The distance measured using sonometry was reproducible and stable, and there was a correlation between sensor distance and the gastric volume measured with barostat. (ii) Simultaneous recordings by sonometry and barostat showed a similar postprandial response, while the postprandial increase of the sensor distance was much smaller without the balloon (3.2+/-0.2 mm vs 9.7+/-1.5 mm, P<0.02). (iii) The sensor distance was increased with gastric electrical stimulation. CONCLUSIONS: Sonometry is able to detect gastric volume changes as validated by gastric perturbations with distensions, food ingestion and electrical stimulation. The postprandial increase in gastric volume measured by sonometry with barostat balloon is greater because of the presence of the intragastric balloon.     

Effect of mianserin on gastric sensorimotor function and gastric emptying: a randomized,placebo‐controlled,double‐blind,crossover study in healthy volunteers

Background Antidepressants such as mianserin can improve symptoms in some functional dyspeptic patients but their mechanism of action remains unclear. We aimed to assess the effects of mianserin on gastric sensorimotor function in man. Methods In this randomized, placebo‐controlled, double‐blind, crossover study 12 healthy subjects (six men) underwent a gastric barostat study and a gastric emptying breath test after 7 days pretreatment with placebo or mianserin (20 mg; p.o.). Graded isobaric and isovolumetric distentions were performed to determine gastric compliance and sensitivity. Subsequently, intrabag pressure was held constant and the volume increase after administration of a liquid meal (200 mL; 300 kcal) was studied. Breath was sampled before and after ingestion of a test meal and half‐emptying times for solids and liquids were determined from the breath samples. Mianserin was compared to placebo using t‐tests and mixed model analysis (mean ± SD). Key Results Mianserin did not affect pressures or volumes needed to induce first perception or discomfort. During isovolumetric distensions compliance was decreased after mianserin treatment (1.8 ± 0.4 vs 2.0 ± 0.3 mmHg 100 mL^?1; P < 0.05). Premeal volumes were comparable in both treatment arms (221 ± 99 vs 220 ± 88 mL), but meal‐induced relaxation during the first 30 min was significantly inhibited after mianserin treatment (F_6,40 = 2.58, P < 0.05). Mianserin did not affect either solid or liquid gastric emptying. Conclusions & Inferences Mianserin does not alter gastric emptying rate or sensitivity to gastric distension, but inhibits gastric accommodation to a meal in its early phase. These observations provide no explanation for the effects of mianserin in functional dyspeptic patients.     

A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia

Abstract  Impaired gastric accommodation, hypersensitivity to distension and delayed gastric emptying are major pathophysiological mechanisms in functional dyspepsia (FD). Acotiamide (Z-338) was well-tolerated in healthy volunteers. To determine the effect of three doses of Acotiamide on major pathophysiological mechanisms, symptoms, quality of life (QOL) and safety in functional dyspeptics. A phase IIa, randomized, double-blind, placebo-controlled study (14, 21 and 28 days, respectively, for run-in, study drug administration and follow-up). Gastric accommodation, sensitivity to distension and gastric emptying were assessed by barostat and ¹³C breath test, symptoms by daily diary cards and QOL by SF-36. A total of 71 patients were enrolled (62 evaluable). There was no effect on gastric emptying and sensitivity to distension. 300 mg was better than placebo for meal accommodation ( P  = 0.024). 100 mg was better than placebo at week 2 for upper abdominal bloating ( P  = 0.001) and overall symptom score ( P  = 0.022), and at week 3 for bloating ( P  = 0.008) and heartburn ( P  = 0.041). 100 mg was also better than placebo for QOL (physical function) ( P  = 0.003). Acotiamide was safe and well-tolerated in patients with FD. The involved mechanism could at least in part depend on an effect on meal-induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated.     

Altered neuroendocrine response and gastric dysmotility in the Flinders Sensitive Line rat

In the search for animal models that can replicate some features of functional dyspepsia (FD) patients, we turned our interest to the Flinders Sensitive Line (FSL) rat. Gastric motility disturbances prevalent in FD patients as well as urine corticosterone and plasma prolactin were measured following buspirone challenge. Flinders Resistant Line (FRL) rat was used as control. The results show that the FSL rats have a disturbed gastric motility, reflected as both an increased gastric accommodation rate and gastric volume during gastric distension as well as a delayed gastric emptying, the latter possibly as a consequence of the former. Lipid administration resulted in a significant increase in maximal gastric volume only in the FRL rats. Both the corticosterone response to buspirone and the 24-h urinary output of corticosterone were normal in FSL rats. Similar to FD patients, the FSL rat showed supersensitivity to buspirone in the increase in prolactin release. Although FSL rats show some features similar to a subset of FD patients, the increased gastric accommodation contrasts to the reduced accommodation often seen in FD patients. Further studies are warranted to determine the relevance of this rat strain as a model for FD.     

Reproducibility of gastric tone, compliance and gastric accommodation assessed with barostat in conscious dogs

The reproducibility of barostat measurements was unclear. In this study, the intraday and interday reproducibility of barostat measurements of gastric tone, compliance and gastric accommodation were assessed in a canine model. A series of experiments were performed using a barostat system in 11 surgically prepared healthy dogs: (i) interday gastric tone and compliance: three sessions on three separate days; (ii) intraday gastric tone and compliance: two sessions on the same day separated by a 30-min interval; (iii) interday gastric accommodation: two sessions on two separate days, with each including a 30-min baseline and a 60-min postprandial period. The results were (i) interday gastric tone (81.2 +/- 7.5 mL vs 89.2 +/- 8.1 mL vs 86.2 +/- 13.6 mL, n = 11) and compliance (n = 8) were comparable; (ii) intraday gastric tone (87.9 +/- 17.2 mL vs 77.0 +/-14.8 mL, n = 8) and compliance (n = 8) was also similar, but with considerable individual variance; (iii) interday gastric accommodation was 320.8 +/-45.1 mL vs 287.9 +/- 31.2 mL, no significant difference (n = 8). Inter- and intraday gastric tone and compliance and interday gastric accommodation were relatively reproducible in most animals when tested under well-controlled conditions. However, considerable variations may occur in fasting gastric tone and compliance measurements in certain individuals and cautions should be given when interpreting related results.     

Influence of ghrelin on the gastric accommodation reflex and on meal-induced satiety in man

Abstract  Ghrelin increases gastric tone in the fasting state and enhances gastric emptying in gastroparesis. The aims of the study were to evaluate the effect of ghrelin on postprandial gastric tone and on meal-induced satiety in health. Ten healthy volunteers underwent a barostat study on two occasions. After determination of intra-abdominal pressure (minimal distending pressure, MDP), isobaric volume measurement was performed for 90 min at MDP + 2 mmHg. After 20 min, ghrelin (40 μg) or saline was administered i.v. over 30 min in a double-blind-randomized cross-over design, followed 10 min later by a liquid meal (200 mL, 300 kcal). Stepwise isobaric distentions (+2 mmHg per 2 min) were performed 60 min after the meal. Data (mean ± SEM) were compared using paired Student's t -test and anova . Separately, a satiety drinking test (15 mL min⁻¹ until satiety score 5) was performed on 10 subjects twice, after treatment with placebo or ghrelin. Ghrelin infusion significantly inhibited gastric accommodation (mean volume increase adjusted means 108.0 ± 50 vs 23.0 ± 49 mL, P  = 0.03, ancova with the premeal postinfusion volume as covariate) and reduced postprandial gastric volumes (197.2 ± 24.6 vs 353.5 ± 50.0 mL, P  = 0.01). Pressures inducing perception or discomfort during postprandial gastric distentions were not altered. During satiety testing, ghrelin did not alter nutrient volume ingested till maximal satiety (637.5 ± 70.9 vs 637.5 ± 56.2 mL, ns). Ghrelin administered during the meal significantly inhibits gastric accommodation in health, but this is not associated with early satiation.     

An audit of technical pitfalls of gastric barostat testing in dyspepsia.

Sensorimotor dysfunction of the proximal stomach is considered an important mechanism for symptom generation in functional dyspepsia and related conditions. Barostat studies are used to assess gastric sensitivity to distention, compliance and meal-induced accommodation. The aim of the present study was to assess tolerance and pitfalls of gastric barostat studies at a tertiary care centre. We performed a retrospective review of patient barostat studies between 01/2000 and 12/2004 at Leuven University Hospital. We evaluated compliance with the procedure, suggestions of air leaks, unusual sensory reporting, baseline intra-balloon volumes, gastric accommodation and phasic contractions after a meal. About 98.1% of 414 scheduled gastric barostat studies were well tolerated and the majority (94.1%) were technically adequate. Interpretation was hampered in 18 (4.4%) studies because of low intra-balloon volumes and in six (1.5%) studies because of suspected air leaks. Negative accommodation was found in 69% of studies with low volumes and in 9.8% of 382 studies with adequate volumes (27% patients with previous antireflux surgery). About 94% of gastric barostat studies in patients with upper gastrointestinal symptoms are well tolerated and technically adequate. Major artefacts are due to air leak or inappropriately low volumes.     

The effect of glucagon-induced gastric relaxation on TLOSR frequency

This study aimed to determine the effect of glucagon-induced gastric relaxation on the frequency of transient lower oesophageal sphincter relaxations (TLOSRs). Eight normal subjects (four male, age 18-52 y) were studied after a 6-h fast using a combined manometric barostat assembly. The recording was divided into two 1-h sessions: (1) a baseline period with the barostat set at minimal distending pressure (MDP) + 2 mmHg and (2) a period with continuous glucagon or placebo infusion with barostat set at MDP + 2 mmHg. Patients were studied on two different days and randomly received glucagon (4.8 microg kg(-1) bolus followed by 9.6 microg kg(-1) h(-1) infusion) on 1 day and placebo (saline) on another. Lower oesophageal sphincter (LOS) pressure, frequency of TLOSRs, and barostat bag volumes were determined for both placebo and glucagon infusion. Glucagon induced significant fundal relaxation compared with placebo (P < 0.05) and significantly decreased baseline LEOS pressure (P < 0.05). The frequency of TLOSRs was not altered by glucagon infusion compared with placebo. Despite causing substantial proximal stomach relaxation, glucagon did not increase TLOSR frequency. This suggests that the relevant gastric mechanoreceptors responsible for triggering TLOSRs do not respond to passive elongation.     

The herbal preparation STW5 (lberogast®) has potent and region-specific effects on gastric motility

Functional dyspepsia (FD) is amongst the most common functional gastrointestinal disorders. Symptomatic treatment includes the use of herbal preparations whose effects on gastric motility are unclear. The present study aimed at investigating the effects of STW 5 (Iberogast), a fixed combination of hydroethanolic herbal extracts, on gastric motility in vitro. Muscle strips from guinea-pig gastric fundus, corpus and antrum were set up in organ baths either in circular or longitudinal orientation. Addition of ethanol-free STW 5 to the organ baths (32-512 microg mL(-1)) dose-dependently evoked a sustained and reversible relaxation of circular and longitudinal fundus and corpus muscle strips without changes in phasic activity. In contrast, antral muscle strips responded to STW 5 with a significant increase in the contractile force of phasic contractions without changes in tone. All effects were resistant to tetrodotoxin (0.5 micromol L(-1)), atropine (1 micromol L(-1)), omega-conotoxin GVIA (0.5 micromol L(-1)), capsaicin (1 micromol L(-1)) or L-NAME (100 micromol L(-1)), suggesting that neither nerves nor nitric oxide pathways were involved. These data demonstrate that STW 5 profoundly alters gastric motility in a region-specific but not layer-specific manner and thus implicates Iberogast in the treatment of FD patients suffering from motility disorders with impaired fundus accommodation and/or antral hypomotility.     

Nitrergic and cholinergic vagal pathways involved in the regulation of canine proximal gastric tone: an in vivo study

To better understand the relationship between cholinergic and nitrergic (NO) innervation in the regulation of proximal gastric (fundic) tone in vivo, the effects of nitric oxide synthase blockade on fundic tone were studied in conscious dogs using vagal cooling and an electronic barostat. Vagal cooling, atropine (0.05 mg kg-1 i. v. bolus) and hexamethonium (1 mg kg-1 i.v. bolus) all markedly decreased fundic tone as reflected by increased intragastric volume, indicating a significant contribution of vagal and enteric cholinergic pathways to the maintenance of canine fundic tone. Administration of L-NNA (10 mg kg-1 i.v. bolus) increased fundic tone and the effects of L-NNA were completely prevented by prior vagal cooling or atropine administration, but not by pretreatment with hexamethonium. The relaxation effects of neurally derived NO appear primarily related to inhibition of ongoing vagal cholinergic activity. The data are consistent with the primary site of action of nitrergic mechanisms on gastric fundic tone in conscious dogs being at a presynaptic site on vagal cholinergic efferent nerves.     

A model for evaluation of gastric sensitivity in awake rats

We developed a model for the evaluation of gastric sensitivity to distension in awake rats. A balloon made from a latex condom was chronically placed in the stomach and three stainless steel electrodes were implanted in the neck muscles. Isobaric distensions were performed with a barostat by step of 5 mmHg with 10 min inflation and 2 min deflation. Gastric pressure, integrated neck electromyogram (EMG) and gastric volume were continuously monitored on a potentiometric recorder. Gastric distension at 15 or 20 mmHg induced a typical posture associated with contractions of the neck muscles. Pain threshold was defined as the pressure inducing an increase of integrated neck EMG greater than 100%.
The mean pain threshold was 18.5 ± 0.7 mmHg and was not modified 2, 4 and 7 days after the first experiment. However, gastric volumes were significantly higher on the 4th and the 7th days. Morphine at the doses of 0.4 and 4 mg kg⁻¹ i.p. significantly increases the pain threshold. At the doses of 0.04 and 0.4 mg kg⁻¹, morphine significantly increased gastric volume for the distending pressure of 10 mmHg. Naloxone (2.5 mg kg⁻¹ i.p.) reversed the effects of morphine. In conclusion, our model permits simultaneous evaluation of pain threshold and gastric compliance associated with gastric distension in conscious rats.