Fasting Gastric Volume Research Articles

Effects of Amitriptyline on Gastric Sensorimotor Function and Postprandial Symptoms in Healthy Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial

Low-dose tricyclic antidepressants have been used to treat chronic somatic and gastrointestinal pain disorders, including refractory functional dyspepsia. However, there are only limited data on the effects of these drugs on upper gastrointestinal function. To compare the effects of two doses of amitriptyline (AMT) and placebo on gastric accommodation, emptying, satiation, and postprandial symptoms in healthy volunteers. Using a parallel-group, double-blind, placebo-controlled design, 41 healthy volunteers were randomized to AMT 25 mg, AMT 50 mg, or placebo for 2 wk. During the final 3 days of therapy, the following end points were assessed: fasting and postprandial gastric volumes, 2- and 4-h gastric emptying, time and volume to maximum satiation using a nutrient drink test, and postprandial symptoms 30 min later using 10-cm visual analog scales. AMT and metabolite levels were measured. AMT slowed gastric emptying at 2 h (median 75% for placebo, 57% for AMT 25 mg, 67% for AMT 50 mg; P= 0.037) and 4 h (median 98% for placebo, 96% for AMT 25 mg, 92% for AMT 50 mg; P= 0.003). AMT did not affect gastric volumes or satiation volume, but it did reduce nausea scores at 30 min in a dose-dependent manner (median 2.1 for placebo, 0.9 for AMT 25 mg, and 0.0 for AMT 50 mg; P= 0.009). In healthy volunteers, AMT slows gastric emptying of solids, but it does not significantly affect gastric volumes or satiation. AMT reduces nausea after challenge with a high calorie liquid load.

Candidate genes and sensory functions in health and irritable bowel syndrome

Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) function; these effects are mediated through G protein transduction. Candidate genetic variations in ADR-SER were significantly associated with somatic scores in irritable bowel syndrome (IBS) and gastric emptying but not small bowel or colonic transit. Our aim was to assess whether candidate ADR-SER genes are associated with motor and sensory GI functions in IBS and subgroups on the basis of bowel dysfunction. In 122 patients with IBS and 39 healthy controls, we assessed gastrointestinal somatic symptoms and affect by validated questionnaires. We measured: gastric volume (GV), maximum tolerated volume, rectal compliance, sensation thresholds and ratings, and genetic variations including alpha2A (C-1291G), alpha2C (Del 332-325), GNbeta3 (C825T), and 5-HTTLPR. Demographics and genotype distributions were similar in the patients with IBS subgrouped on bowel function. There were significant associations between 5-HTTLPR SS genotype and absence of IBS symptoms and between 5-HTTLPR LS/SS genotype and increased rectal compliance and increased pain ratings, particularly at 12 and 24 mmHg distensions. GNbeta3 was associated only with fasting GV; we did not detect associations between alpha2A genotype and the gastrointestinal sensory or motor functions tested. We concluded that 5-HTTLPR LS/SS genotype is associated with both increased pain sensation and increased rectal compliance though the latter effect is unlikely to contribute to increased pain sensation ratings with LS/SS genotype. The data suggest the hypotheses that the endophenotype of visceral hypersensitivity in IBS may be partly related to genetic factors, and the association of GNbeta3 with fasting GV may explain, in part, the reported association of GNbeta3 with dyspepsia.

Genetic variation in endocannabinoid metabolism, gastrointestinal motility, and sensation

Cannabinoid agonist inhibits gastrointestinal motility. The endocannabinoid, anandamide, is inactivated by fatty acid amide hydrolase (FAAH). A single nucleotide polymorphism in the human FAAH gene (C385A) reduces FAAH expression. Our aim was to evaluate associations between FAAH genotype variation and symptom phenotype, gastric emptying and volume, colonic transit, and rectal sensation in patients with functional gastrointestinal disorders (FGID). 482 FGID patients [Rome II positive, 159 constipation disorders, 184 diarrhea disorders (D-IBS), 86 mixed bowel function (M-IBS), 20 chronic abdominal pain (CAP), 33 functional dyspepsia], and 252 healthy volunteers (HV) underwent questionnaires and studies of phenotype and genotype from 2000 to 2007: 250 gastric emptying, 210 fasting and postprandial gastric volume, 152 colonic transit, and 123 rectal sensation. All had FAAH genotype [CC vs. polymorphic (CA/AA)] determined by TaqMan. FAAH genotype distribution of FGID patients and HV did not deviate from Hardy-Weinberg equilibrium. There was a significant association of FAAH genotype with FGID phenotype (overall chi(2), P = 0.011) and with specific individual phenotypes (P = 0.048). Thus FAAH CA/AA increases the odds (relative to HV) for D-IBS (P = 0.008), M-IBS (P = 0.012), and, possibly, CAP (P = 0.055). There was a significant association of FAAH CA/AA genotype with accelerated colonic transit in D-IBS (P = 0.037). There was no association of FAAH genotype with rectal sensation thresholds or ratings. The association of genetic variation in metabolism of endocannabinoids with symptom phenotype in D-IBS and M-IBS and with faster colonic transit in D-IBS supports the hypothesis that cannabinoid mechanisms may play a role in the control of colonic motility in humans and deserve further study.

Potential of Intestinal Electrical Stimulation for Obesity: A Preliminary Canine Study

The aims of this study were to investigate the therapeutic potential of intestinal electrical stimulation (IES) for obesity. Experiments were performed to investigate the effects of IES on food intake, gastric tone, gastric accommodation, and its possible pathway. Ten normal dogs and six dogs with truncal vagotomy were used in this study. Each dog was equipped with a gastric cannula for the measurement of gastric tone and accommodation by barostat and one pair of duodenal serosal electrodes for IES. The experiment on food intake was composed of both control session without IES and IES session after a 28-hour fast. The experiment on gastric tone and accommodation was performed in the fasting and fed states and composed of three sessions: control, IES, and IES with N(G)-nitro-l-arginine. IES significantly reduced food intake in the normal dogs (459.0 vs. 312.6 grams, p < 0.001). The food intake was negatively correlated with the fasting gastric volume during IES. IES significantly decreased fasting gastric tone in the normal dogs reflected as a decrease in gastric volume (89.1 vs. 261.3 mL, p < 0.01), which was abolished by vagotomy and N(G)-nitro-l-arginine. IES reduces food intake and inhibits gastric tone in the fasting state. The inhibitory effect of IES on gastric tone is mediated by both vagal and nitrergic pathway.

A double‐blind, randomized, placebo‐controlled trial of itopride (100 and 200 mg three times daily) on gastric motor and sensory function in healthy volunteers

Itopride, a dopamine D2 antagonist and acetylcholinesterase inhibitor, significantly improved symptoms in patients with functional dyspepsia in one phase II randomized trial. However, the mechanisms by which itopride may improve symptoms are unknown. We aimed to compare the effects of two doses of itopride and placebo on gastric volumes, gastric emptying, small bowel transit and satiation in female and male healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of itopride 100 mg (n = 16) or 200 mg (n = 15) or placebo (n = 15) t.i.d. Validated methods were used to study gastric accommodation (single photon emission computed tomography), gastric emptying and orocecal transit and satiation postnutrient challenge. The three arms were comparable with regard to age, gender and body mass index. There were no statistically significant effects of itopride on gastric emptying, orocecal transit, fasting gastric volume, maximum tolerated volume or aggregate symptom score with nutrient drink challenge. Postprandial (PP) change in gastric volume differed in the three groups (P = 0.019): 625[+/-28 (SEM)], 555(+/-26) and 512(+/-33) in placebo, itopride 100 and 200 mg groups, respectively. In healthy subjects, itopride reduced total PP gastric volume without accelerating gastric emptying or significantly altering gastric motor and sensory function in healthy individuals.

Inhibitory effects of sildenafil on gastric motility and gastric slow waves in dogs

The aim of this study was to investigate the effects of sildenafil on gastric motility and gastric slow waves in dogs. The study was performed in healthy dogs and composed of three experiments. The first experiment was designed to study the effects of sildenafil on gastric emptying and gastric slow waves. The second experiment was used to investigate the effects of sildenafil on gastric tone. The third experiment was used to study the effects of sildenafil on postprandial antral contractions. (i) Sildenafil did not alter gastric emptying of liquid. (ii) Sildenafil had no effects on dominant frequency and percentage of normal gastric slow waves. The dominant power of gastric slow waves was, however, significantly reduced with sildenafil (P < 0.02). (iii) Fasting gastric volume with sildenafil was significantly higher than that at baseline (P < 0.0005) or in the control session (P < 0.002). However, the postprandial gastric volume was not altered with sildenafil. (iv) Sildenafil inhibited gastric antral motility. The contraction index was 338.5 +/- 39.99 at baseline and 122.5 +/- 20.3 after the injection of sildenafil (P = 0.003). Sildenafil inhibits fundic tone and antral motility but does not seem to delay gastric emptying of liquid in dogs. The amplitude but not the frequency or regularity of the gastric slow wave is inhibited by sildenafil.

Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults

The incretin glucagon-like peptide-1 (GLP-1), which is used to treat diabetes mellitus, delays gastric emptying by inhibiting vagal activity. GLP-1 also increases fasting and postprandial gastric volume in humans. On the basis of animal studies, we hypothesized that nitric oxide mediates the effects of GLP-1 on gastric volumes. To assess the effects of nitrergic blockade on GLP-1-induced gastric accommodation in humans, in this double-blind study, 31 healthy volunteers were randomized to placebo (i.e., saline), GLP-1, or the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine acetate (L-NMMA; 4 mg.kg(-1) x h(-1)) alone or with GLP-1. Thereafter, 16 additional subjects were randomized to GLP-1 alone or together with a higher dose of L-NMMA (10 mg/kg bolus plus 8 mg.kg(-1).h(-1) infusion). Gastric volumes (fasting pre- and postdrug, postprandial postdrug) were measured by (99m)Tc-single-photon-emission computed tomography imaging. GLP-1 increased (P = 0.04) fasting gastric volume by 83 +/- 16 ml (vs. 17 +/- 11 ml for placebo) and augmented (P < or = 0.01) postprandial accommodation by 688 +/- 165 ml (vs. 542 +/- 29 ml for placebo). L-NMMA (low dose) alone did not affect fasting or postprandial gastric volume. L-NMMA (low dose) did not attenuate the effect of GLP-1 on gastric volumes. In contrast, L-NMMA (high dose) did not affect fasting volume but blunted GLP-1-mediated postprandial accommodation (postprandial change = 494 +/- 37 ml, P < or = 0.01 vs. GLP-1 alone). These data are consistent with the hypothesis that nitric oxide partly mediates the effects of GLP-1 on postprandial but not fasting gastric volumes in humans.

Effect of different macronutrients in excess on gastric sensory and motor functions and appetite in normal-weight, overweight, and obese humans

Background:The effects of supplementation with different macronutrients on gastric sensory and motor functions are unclear.Objective:We aimed to compare the effects of 2 wk of supplementation with different classes of macronutrients on gastric function, satiation, and appetite in healthy and overweight subjects.Design:In a parallel-group, double-blind study, 52 (14 men, 38 women) healthy normal-weight, overweight, and obese participants [body mass index (BMI; in kg/m2): 19.4–47.0] aged 18–64 y were randomly assigned to consume different isocaloric diets (n= 13 per diet group) adjusted for BMI and activity level. The standard diet provided 20% of energy as protein, 30% as fat, and 50% as carbohydrate. The high-protein, high-fat, and high-carbohydrate diets contained 500 additional kcal in each nutrient class. On 3 separate days, we measured gastric emptying of solids, gastric volumes, postprandial symptoms, appetite, and food choice with validated methods. Age, sex, BMI, and baseline satiation were covariates in the analysis of covariance.Results:Fat supplementation was associated with increased maximum tolerated volume (MTV) in subjects with a high baseline MTV (P< 0.05), irrespective of BMI. Gastric emptying and volumes, postprandial symptoms, total calories, and food choices at an ad libitum meal were not significantly different after each dietary preload. Fasting gastric volumes tended to be higher with the high-fat than with the high-carbohydrate or high-protein diets (P≤ 0.1). Gastric emptying and volumes and satiation were not significantly different between the BMI categories (< and >30).Conclusion:Supplementation with 500 kcal fat in excess of required calories for 2 wk increased food tolerance in healthy normal-weight and obese subjects with a high baseline MTV without significantly changing gastric motor functions.

Gastric Electrical Stimulation With Parameters for Gastroparesis Enhances Gastric Accommodation and Alleviates Distention-Induced Symptoms in Dogs

Gastric electrical stimulation (GES) improves symptoms in patients with gastroparesis. We sought to determine if stimulation at fundus with parameters used for gastroparesis could affect gastric accommodation and distention-induced symptoms in dogs. Nine dogs were implanted with a gastric cannula at the anterior stomach and 1 pair of stimulation electrodes in the fundus. Assessment of gastric accommodation and a series of gastric distention were performed using a barostat. Stimulation parameters were of short pulse trains of 14 Hz, 5 mA, 0.3 ms, and 0.1 s on, 5 s off. GES at fundus significantly decreased fasting gastric tone. Fasting gastric volume was significantly increased from 56.3+/-10.4 mL at baseline to 102.4+/-23.1 mL with stimulation (P=.011). Postprandial gastric accommodation was significantly enhanced with stimulation. The extent of accommodation increased from 249.3+/-39.9 mL in the control session to 325.8+/-25.1 mL with stimulation (P=.011). Symptom scores induced by balloon distention of the stomach were significantly lower during stimulation in comparison with those of baseline (P=.016). In conclusion, GES with parameters for gastroparesis enhances postprandial gastric accommodation and reduces visceral perception in normal dogs. This effect, if seen also in humans, may explain in part the symptomatic improvement associated with GES therapy in patients with gastroparesis.

Obesity Does Not Increase Effects of Synthetic Ghrelin on Human Gastric Motor Functions

Ghrelin is secreted by the stomach and stimulates food intake. Obese individuals have lower fasting plasma ghrelin levels but increased appetite, suggesting greater responses to endogenous ghrelin in obesity. The aim of this study was to compare effects of exogenous ghrelin (at a dose that stimulates growth hormone [GH] release in the physiologic range) versus placebo on gastric emptying, gastric volume, and postprandial symptoms and determine whether body mass (ranging from normal weight to obesity) influences responses to ghrelin. After intravenous bolus synthetic human ghrelin (0.33 mug/kg) or saline, we measured plasma GH, gastric volume, and gastric emptying by combined (99m)Tc-single-photon emission computed tomography and scintigraphy ((111)In egg meal, 300 kcal) and postprandial symptoms using visual analogue scales. In 25 obese subjects (5 men and 20 women; body mass index [BMI], 36 +/- 4 kg/m(2)) and 13 female normal-weight (BMI, 22 +/- 2 kg/m(2)) subjects of similar ages, ghrelin increased GH levels (15.0 +/- 2.4 ng/mL) at 40 minutes postinjection and tended to decrease fasting gastric volumes compared with placebo (P = .059). There were no effects of BMI on treatment response and no differences between ghrelin and saline on postprandial (P = .09) or change in (postprandial minus fasting) gastric volumes, gastric emptying, or aggregate postprandial symptoms. Effects of ghrelin did not differ between obese and normal-weight participants. At doses that stimulate physiologic GH plasma levels, synthetic ghrelin tended to decrease fasting gastric volumes without altering postprandial volumes or gastric emptying in a predominantly female cohort. The data are not consistent with the hypothesis that higher body mass is associated with increased gastric responsiveness to ghrelin.

Effect of a proton pump inhibitor on postprandial gastric volume, emptying and symptoms in healthy human subjects: a pilot study

In consensus guidelines, proton pump inhibitors (PPIs) are recommended for the treatment of functional dyspepsia. It is unclear whether PPIs change gastric volume or emptying. To assess the effect of a PPI, rabeprazole, on gastric volume and emptying and postprandial symptoms. In a double-blind, parallel-group placebo-controlled trial, 13 healthy participants were randomized to rabeprazole, 20 mg b.d., or placebo. On day 3, fasting gastric volume was measured using intravenous (99m)Tc-pertechnate and single photon emission computed tomography (SPECT). After the last dose of study medication, an (111)In-chloride egg meal (300 kcal) was ingested, and postprandial gastric volume and emptying were measured by SPECT. Symptom ratings using a visual analogue scale (fullness, nausea, bloating, abdominal pain, aggregate score) were obtained at baseline and 15, 30, 45, 60 and 75 min postprandially. Group comparisons were performed using Mann-Whitney rank sum test. There were no statistically significant differences in gastric volume or emptying in the two groups. However, there was a borderline increase in gastric volume with rabeprazole compared with placebo. Rabeprazole treatment reduced aggregate postprandial symptoms, particularly fullness, 30 min after the meal (P = 0.01). In healthy participants, rabeprazole, 20 mg b.d., did not significantly change gastric emptying, but reduced symptoms and had a borderline effect on gastric volume postprandially. The mechanism of reduced postprandial symptoms with a PPI requires further study.

Effect of a cannabinoid agonist on gastrointestinal transit and postprandial satiation in healthy human subjects: a randomized, placebo‐controlled study

Cannabinoid receptor (CBR) stimulation inhibits motility and increases food intake in rodents. Effects of CBR stimulation in human gastrointestinal (GI) tract are unclear. We compared effects of dronabinol (DRO) and placebo (PLA) on GI transit, gastric volume and satiation in humans. In a double-blind, randomized study, 30 healthy volunteers were randomly assigned to DRO 5 mg b.i.d. or PLA for three doses. We measured GI functions noninvasively: day 0, Ensure satiation test to measure maximum tolerated volume (MTV) and 30-min post-Ensure symptoms; day 1, scintigraphic transit ((111)In-egg meal) and fasting and postprandial gastric volume ((99Tcm)-SPECT); day 2, 24-h colonic transit and repeat satiation test. ancova was used to compare treatment groups with gender, age, and, for the satiation test, the baseline MTV, as covariates. A log-rank test was used to assess treatment effects on gastric emptying. Planned sample size had 80% power to detect 25-30% differences in primary end points. There was an overall retardation of gastric emptying with DRO (P = 0.018); this was more pronounced in females (P = 0.011), than in males (P = 0.184). No significant treatment differences were detected for gastric volumes, MTV, post-Ensure(R) symptoms, small bowel and colonic transit. Fasting gastric volume was greater in males receiving DRO compared with PLA (238 +/- 17 vs 185 +/- 16, P = 0.04). DRO retards gastric emptying in humans; effects are gender-related. Dronabinol also increases fasting gastric volumes in males.

Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers

Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 microg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink ("satiation") test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.

Gastric or intestinal electrical stimulation-induced increase in gastric volume is correlated with reduced food intake

Objective. Satiation has recently been shown to be associated with gastric volume or gastric tone. Electrical stimulation has been shown to reduce food intake and increase gastric volume, or reduce gastric tone. The aim of this study was to investigate the correlation between gastric or intestinal electrical stimulation (GES/IES)-induced increase in gastric volume and food intake. Material and methods. GES/IES was performed on 14 dogs implanted with electrodes and a gastric cannula. Food intake was measured and gastric volume was assessed using barostat with or without GES/IES. Results. Food intake was correlated to weight (r=0.62, p = 0.02) as well as the fasting gastric volume (r=0.59, p=0.02). GES/IES reduced food intake (240.8 versus 445.0 g, p<0.005) and increased gastric volume in the fasting state (263.4 versus 74.4 ml, p<0.0001). Reduced food intake was correlated to the preprandial gastric volume (r= − 0.58, p=0.02) and postprandial increase in gastric volume with GES/IES (r=0.56, p=0.03). Conclusions. GES/IES reduces food intake and increases gastric volume measured by barostat. The GES/IES-induced increase in gastric volume (or reduced gastric tone) is correlated with reduced food intake during GES/IES.

Pyloromyotomy: technique and use for gastric drainage combined with vagotomy.

Abstract Gastric drainage must accompany vagotomy and for this purpose gastro-enterostomy and pyloroplasty are equally effective. When the stomach requires to be extensively mobilized, as for high oesophagogastric anastomoses, these drainage operations interfere with important collateral vessels and they may impede mobilization of the stomach by shortening or anchoring the gastric outlet. In this situation both internal pyloric stretching and stretch pyloromyotomy have, over a period of 10 years, provided effective gastric drainage. Internal pyloric stretching without myotomy would seem to be the ideal decompressive manoeuvre for cases of high gastrooesophagectomy. Pyloric stretching with or without myotomy has been used in 56 cases of transthoracic hiatus hernia repair accompanied by vagotomy for associated duodenal ulcers. The technique was used originally only because it was simpler than a pyloroplasty to perform through a left thoracotomy. On the basis of postoperative symptoms, gastric emptying times, and fasting gastric secretion volumes, it has proved as effective as other drainage procedures provided duodenal or pyloric fibrosis is absent or minimal. The technique permits of accurate hernia repair with vagotomy through a standard left thoracotomy.

Contribution of Ascites to Impaired Gastric Function and Nutritional Intake in Patients With Cirrhosis and Ascites

Protein calorie malnutrition and weight loss are common among patients with cirrhosis and ascites. The cause of these symptoms is unclear, with several putative mechanisms proposed. The primary aims of this study were to compare gastric volumes and accommodation between patients with cirrhosis complicated by ascites and healthy controls, and to evaluate the effect of large-volume paracentesis in the patient group. Patients with cirrhosis and ascites underwent assessment of gastric volumes as measured by single-photon emission computed tomography, gastric sensation assessed by a validated nutrient drink test, and a 3-day assessment of caloric intake before and after large-volume paracentesis. Age- and sex-adjusted linear regression models were used to compare gastric volumes and accommodation ratios between patients and healthy volunteers. Paired Wilcoxon rank-sum tests were used to compare gastric measures before and after paracentesis among the patient group. Fifteen patients (median age, 54 y) were compared with 112 healthy (age- and sex-matched) controls. Median postprandial gastric volumes (627 mL patients vs 721 healthy controls) and gastric accommodation were reduced significantly in patients compared with healthy controls (P = .02 and .006, respectively). After paracentesis: (1) fasting gastric volumes were increased (median 312 mL post- vs 241 mL pre-, P = .04), (2) patients tolerated ingestion of larger maximum volumes (median 964 mL post- vs 738 mL pre-, P = .04), and (3) caloric intake was increased (median 34% kcal post- vs 3110 kcal pre-, P = .005). Postprandial gastric volumes and accommodation ratios are reduced in patients with cirrhosis and ascites compared with healthy controls. In addition, large-volume paracentesis increases fasting gastric volumes, volumes ingested until maximal satiation, and caloric intake.

Effect of Gastric Volume or Emptying on Meal-Related Symptoms After Liquid Nutrients in Obesity: A Pharmacologic Study

Altered postprandial satiation influences food intake in obesity. The aim of this study was to evaluate the contribution of gastric motor functions to intra- and postprandial symptoms in obese, otherwise healthy, people. In a randomized, parallel-group, double-blind design, 40 obese (body mass index>30 kg/m2) healthy volunteers (n=10/group) received intravenous saline (placebo), atropine (.02 mg/kg), or erythromycin (1 or 3 mg/kg) to alter gastric volume and emptying after liquid nutrient meals, measured by validated imaging methods. The nutrient drink test assessed the volume ingested at maximum satiation, and intra- and early postprandial symptoms. Relationships between gastric motor functions, meal size, and symptoms were assessed by using multiple regression. Circulating levels of candidate upper-gut hormones involved in satiation were measured. Relative to placebo, atropine retarded gastric emptying and increased gastric volumes; erythromycin accelerated gastric emptying and reduced gastric volumes during fasting. Although similar maximal tolerated volumes were recorded across treatments, intra- and immediate postprandial symptoms were increased by these perturbations, particularly nausea and bloating. Upper-gut hormonal profiles generally reflected changes in gastric emptying. Regression analysis showed that fasting predrug gastric volume was a significant predictor of intra- and postprandial bloating. Change in gastric volume postdrug or postmeal did not contribute additionally to predicting intra- or postprandial symptoms. There was significant (negative) association between gastric emptying and fullness score, and significant (positive) association with hunger score 30 minutes postprandially. In obese individuals, fasting gastric volumes and gastric emptying, but not postprandial gastric volumes, were associated with intra- and postprandial symptoms. Understanding the determinants of gastric volume may provide insights on mechanisms controlling satiation.

Effect of modulation of serotonergic, cholinergic, and nitrergic pathways on murine fundic size and compliance measured by ultrasonomicrometry.

Reduced fasting or postprandial gastric volumes have been implicated in the pathophysiology of functional dyspepsia. The mechanisms that underlie the control of gastric fundic volume are incompletely understood, partly because of an inability to accurately measure fundic volume in vivo in small animals. Small animals are useful models to evaluate mechanisms, e.g., in knockout animals. The aim of this study was to determine whether an ultrasonometric technique accurately monitors fundic contraction and relaxation in mice in vivo and to determine the effect of modulation of cholinergic, nitrergic, and serotonergic pathways on fundic size and compliance in the intact mouse innervated stomach. Two to four piezoelectric crystals (diameter 1 mm, 24-microm resolution) were glued to the serosal side of fundus and used to measure distance. Validation studies showed excellent correlation between measured changes and actual changes in distances between crystals and excellent reproducibility. The expected responses to pharmacological modulation with bethanechol and nitroglycerin were demonstrated. Atropine increased the distance between the crystals, suggesting a baseline cholinergic regulation of fundic volume. Bethanechol, Nomega-nitro-L-arginine, and the 5-HT1B/D agonist sumatriptan decreased the distance between the crystals, suggesting fundic contraction. Atropine, nitroglycerin, and buspirone caused an increase in intercrystal distance consistent with fundic relaxation. Fundic compliance was investigated by changing intragastric pressure via an implanted catheter. Sumatriptan increased compliance, whereas buspirone increased the distance between crystals but did not change compliance. The data suggest that ultrasonomicrometry is a useful tool that can reproducibly and accurately measure changes in fundic size and the response to pharmacological agents.

Effect of Somatostatin Analog on Postprandial Satiation in Obesity

Altered satiation may impact postprandial symptoms and potentially change food intake in obesity. Our aim was to compare effects of octreotide and placebo on postprandial symptoms, satiation, and gastric volumes in obesity. In a randomized, parallel-group, double-blind, placebo-controlled study, 26 obese but otherwise healthy participants received 100 mug of octreotide or placebo subcutaneously 30 minutes before each study. Studies were performed on 2 separate days and included validated non-invasive techniques: (99m)Tc-single photon emission computed tomography imaging to measure fasting stomach volume and gastric volume changes after 90 mL of water and 240 mL of Ensure and a standardized nutrient drink test to measure the maximum tolerated volume and postprandial symptoms. Relative to placebo, octreotide increased gastric volume after 90 mL of water; however, fasting and gastric volume change post-Ensure and maximum tolerated volume of Ensure were not different. Octreotide decreased sensations of fullness (p = 0.035) and bloating (p = 0.05) and tended to reduce aggregate symptoms (p = 0.07) after the fully satiating meal. In obese individuals, somatostatin analog significantly reduced postprandial sensations after a satiating meal without altering maximum tolerated meal volume or postnutrient gastric volume, suggesting an effect on upper gut sensation. The role of somatostatin as a permissive factor in the development of obesity by reducing postprandial sensations deserves further study.

Effect of Metoclopramide on Gastric Fluid Volumes in Diabetic Patients Who Have Fasted before Elective Surgery

Diabetes-induced gastroparesis is believed to increase fasting gastric fluid volume before elective surgery. Metoclopramide is routinely administered preoperatively to reduce gastric fluid volume in these patients. This study compared nondiabetic controls to non-insulin-dependent and insulin-dependent diabetics to determine the effect of metoclopramide, administered before surgery, on gastric volumes in patients who fasted before surgery. Control and diabetic patients fasted preoperatively before receiving either placebo or 10 mg intravenous metoclopramide 20 min before induction of anesthesia. After intubation, a gastric tube was placed, and stomach contents were aspirated with volumes compared among the groups. Both groups of diabetic patients were older than the control group, and insulin-dependent patients had a higher incidence of comorbidities compared with the non-insulin-dependent group. Fasting blood sugar and hemoglobin A1C values were higher in both insulin-dependent and non-insulin-dependent patients. Gastric fluid volumes were similar in control, non-insulin-dependent, and insulin-dependent patients (8.0 +/- 2.6 vs. 9.6 +/- 4.1 vs. 17.7 +/- 2.5 ml, respectively). In insulin-dependent diabetic patients, metoclopramide decreased gastric volume compared with placebo treatment (17.7 +/- 2.5 vs. 7.8 +/- 2.9 ml; P = 0.027). After stratification, a subpopulation of patients with poorly controlled diabetes, regardless of type, were identified to have increased gastric residual volumes. In elective surgical patients who have fasted before surgery, gastric volumes are minimal, even in diabetics with severe neuropathic symptoms. Metoclopramide prophylaxis to reduce gastric volumes seems to be unnecessary unless the patient has a prolonged history of poor blood glucose control.