Emptying In Animals Research Articles

Differential effects of sheep and cow skim milk before and after fermentation on gastrointestinal transit of solids in a rat model

Fermentation of milk is considered to improve ease of digestion. The protein composition of sheep milk differs from cow milk. We hypothesized that sheep milk would produce bioactive properties with different effects on gastrointestinal (GI) motility compared with cow milk and that this would also differ following fermentation. We compared the effect of sheep and cow milk drinks, pre and post fermentation, fed to rats over two weeks, on the rate of GI transit of beads over 12-hours using X-ray imaging. Stomach emptying in animals fed sheep yoghurt was more complete than that for cow yoghurt. GI transit was increased for sheep milk treated animals than for cow milk, and colonic transit was increased, with a similar pattern observed for the yoghurts. The increased colonic transit for sheep milk compared with cow milk reveals prominent species differences, regardless of whether or not the milk was fermented.

Retention of acetaminophen in an in vitro model of solid-phase gastric emptying of animals

To apply an in vitro model for assessment of the solid-phase binding capacity of acetaminophen and thus assess the reliability of this marker for evaluation of solid-phase gastric emptying in vivo in animals. 4 test meals. A spectrophotometric method for detection of acetaminophen was validated and applied for assessment of the percentage retention of acetaminophen in the solid phase of 4 test meals. The gastric milieu was simulated by incubating each meal in artificial gastric juice for 2 hours in a shaking water bath maintained at 37 degrees C. Solid-phase retention was then assessed 3 times by measuring the amount of acetaminophen that had leached into the liquid phase. Acetaminophen was poorly retained in the solid phase of all the test meals examined in the study. There was also a large degree of variability in the percentage retention for each meal when the experiment was repeated 3 times. Analysis of the results of this in vitro study confirmed that acetaminophen may not be an appropriate marker of solid-phase gastric emptying. The acetaminophen gastric emptying test should be applied only for the assessment of liquid-phase emptying in animals.

Pharmacological and Pharmacokinetic Aspects of Functional Gastrointestinal Disorders

Medications are commonly used for the treatment of patients with functional gastrointestinal disorders. The general goal of this report is to review the pharmacokinetics and pharmacology of medications used in functional gastrointestinal disorders. Methods included literature review, consensus evaluation of the evidence for each topic assigned originally to 1 or 2 authors, and broader review at a harmonization session as part of the Rome III process. This report reviews the animal models that have been validated for the study of effects of pharmacologic agents on sensation and motility; the preclinical pharmacology, pharmacokinetics, and toxicology usually required for introduction of novel therapeutic agents; the biomarkers validated for studies of sensation and motility end points with experimental medications in humans; the pharmacogenomics applied to these medications and disorders; and the pharmacology of agents that are applied or have potential for treatment of functional gastrointestinal disorders, including psychopharmacologic agents. Clinician and basic investigators involved in the treatment or investigation of functional gastrointestinal disorders or disease models need to have a comprehensive understanding of a vast range of medications. It is anticipated that the interaction between investigators of basic science, basic and applied pharmacology, and clinical trials will lead to better treatment of these disorders.

Ghrelin gastrokinetic action in patients with neurogenic gastroparesis

Ghrelin has been shown to accelerate gastric emptying in animals where its effect appeared mediated through the vagus nerve. We aimed to verify the gastrokinetic capacity of ghrelin in human. Patients with gastroparesis attributed to a neural dysregulation by diabetes ( n = 5) or surgical vagotomy ( n = 1) were evaluated. The emptying of a test meal (420 kcal) was determined by the C 13 octanoic acid breath test. Saline or synthetic ghrelin 1–4 μg/kg were given in 1 min bolus at the end of the meal. T-lag and T-1/2 were shorter during ghrelin than during saline administration [33 ± 5 min versus 65 ± 14 min ( p < 0.01) and 119 ± 6 min versus 173 ± 38 min ( p < 0.001)]. Ghrelin injection therefore accelerated gastric emptying of a meal in humans even in presence of a deficient gastric innervation.

The effect of bacterial lipopolysaccharide on gastric emptying in rats suffering from moderate renal insufficiency.

The objective of the present study was to evaluate the response of rats suffering from moderate renal insufficiency to bacterial lipopolysaccharide (LPS, or endotoxin). The study involved 48 eight-week-old male SPF Wistar rats (175-220 g) divided into two groups of 24 animals each. One group underwent 5/6 nephrectomy while the other was sham-operated. Two weeks after surgery, the animals were further divided into two subgroups of 12 animals each and were fasted for 20 h but with access to water ad libitum. One nephrectomized and one sham-treated subgroup received E. coli LPS (25 micrograms/kg, i.v.) while the other received a sterile, pyrogen-free saline solution. Gastric retention (GR) was determined 10 min after the orogastric infusion of a standard saline test meal labeled with phenol red (6 mg/dl). The gastric emptying of the saline test meal was studied after 2 h. Renal function was evaluated by measuring the plasma levels of urea and creatinine. The levels of urea and creatinine in 5/6 nephrectomized animals were two-fold higher than those observed in the sham-operated rats. Although renal insufficiency did not change gastric emptying (median %GR = 26.6 for the nephrectomized subgroup and 29.3 for the sham subgroup), LPS significantly retarded the gastric emptying of the sham and nephretomized groups (median %GR = 42.0 and 61.0, respectively), and was significantly greater (p < 0.01) in the nephrectomized rats. We conclude that gastric emptying in animals suffering from moderate renal insufficiency is more sensitive to the action of LPS than in sham animals.

Multiple-breath washout and washin experiments in steers

Multiple-breath N2 washouts (WO) and washins (WI) were performed during regular tidal breathing in 11 unsedated healthy steers approaching pulmonary functional maturity (mean body weight = 271 kg). They inspired 20% O2 in 80% Ar during the WO and air during the WI. For each steer, we computed two indexes of ventilation inhomogeneity from the N2 WO curves: 1) the curvilinearity of the logarithm of end-tidal N2 concentrations as a function of cumulative expired volume reflected in the ratio of two slopes fitted between 100 and 50% and between 50 and 10%, respectively, of end-tidal N2 concentration of the first breath of the WO; and 2) the N2 phase III slope divided by the mean expired concentration (Sn) of each breath also plotted as a function of cumulative expired volume. Equivalent computation of both parameters was done on WI and WO curves, and similar results were obtained. The mean slope ratio was 0.812 +/- 0.119 (SD) for all the steers, which is consistent with topographic gravity-dependent specific ventilation distribution inhomogeneity. Sn was independent of the breath number both for WO and WI (mean Sn = 0.130 +/- 0.057 liters-1), suggesting that emptying between unequally ventilated units, is synchronous. This behavior resembles that observed in rats postmortem (S. Verbanck, E.R. Weibel, and M. Paiva. J. Appl Physiol. 71: 847-854, 1991) but contrasts with experiments in humans, in whom convection-dependent ventilation inhomogeneities generate a marked increase in Sn throughout the entire WO (A. B. H. Crawford, M. Makowska, M. Paiva, and L. A. Engel. J. Appl. Physiol. 59: 838-846, 1985). This is surprising because one would expect gravity-dependent sequential emptying in animals of this size.

Gastric Stasis of Solids after Roux Gastrectomy: Is the Jejunal Transection Important?

To investigate the effect of jejunal transection on the rate of gastric emptying after Roux gastrectomy, a two-part study was conducted. First, we investigated the relationship between Roux limb slow wave frequency and gastric emptying of solids. Six dogs underwent Ronx-en-Y gastrectomy with vagal preservation and placement of intestinal electrodes. Gastric emptying studies were performed on each animal with simultaneous pacing of the Roux limb, either at the slowest rate ( P min) or the fastest rate ( P max) at which entrainment could be achieved. Gastric emptying studies were also performed in the unpaced (control) condition. Gastric half-emptying times ( X̄ ± SEM minutes) and slow wave frequencies ( X̄ ± SEM cycles per minute), respectively, were P min 117 ± 26 min, 15.7 ± 0.1 cpm; P max 97 ± 18 min, 19.0 ± 0.3 cpm; and unpaced 127 ± 16 min, 15.1 ± 0.3 cpm. The gastric half-emptying time during P max was significantly lower than unpaced controls ( P = 0.01). The second part of the study sought to determine if transecting the intestine at 10 cm distal to the pylorus rather than at 20 cm distal to the ligament of Treitz would improve gastric emptying in animals with a truncal vagotomy and Roux-en-Y gastrectomy, Gastric half-emptying times were 149 ± 21 and 164 ± 24 min (ns), respectively. Slow wave frequencies were 17.01 ± 0.06 and 15.7 ± 0.17 cpm ( P < 0.05), respectively. The Roux limb with the more proximal transection converted to the normal fed state pattern on 10 of 15 recording sessions, whereas the group with the more distal transection converted on 5 of 24 recording sessions ( P < 0.05). In conclusion, the decrease in Roux limb slow wave frequency following Roux-en-Y gastrectomy contributes to delayed gastric emptying. Although performing the transection more proximally slightly increases Roux limb slow wave frequency, this alone is insufficient to significantly improve the rate of gastric emptying of solids.

Acceleration of gastric emptying with electrical stimulation in a canine model of gastroparesis.

We investigated the effects of electrical stimulation of the stomach on gastric emptying and the electrical activity of the stomach in 10 dogs. A model of gastroparesis was developed in five dogs using truncal vagotomy combined with injections of glucagon. Glucagon also induced electrical dysrhythmias. Bipolar electrodes were implanted in the stomach and the duodenum for electrical stimulation and for recording electrogastrograms. Gastric emptying of an isotope-labeled solid meal was assessed for 2 h. External electrical stimulation was delivered to the corpus of the stomach at its own physiological frequency to investigate whether it could restore normal gastric emptying. Such stimulation had no significant effect on gastric emptying in intact animals (45 vs. 43%: retention of isotope after 2 h) or when only vagotomy was performed (78 vs. 66%), but it significantly accelerated gastric emptying in animals with vagotomy and glucagon (from 86 to 68%). From this model of delayed gastric emptying, we suggest that electrical stimulation of the stomach at its own intrinsic frequency may recoordinate uncoupled slow wave activity induced by glucagon after vagotomy thus improving the rate of gastric emptying.

Effects of the 5‐HT3 receptor antagonist ICS 205‐930 on fat‐delayed gastric emptying and antral motor activity.

1. The selective 5-HT3 receptor antagonist, ICS 205-930 (Sandoz), has been reported to have potent effects on gastric smooth muscle in vivo and to enhance gastric emptying in animals and in man. 2. This study investigated the effects of ICS 205-930 on fat-delayed gastric emptying of a semisolid meal and antral motor activity in humans. 3. Twelve healthy men participated in each of three studies in which 10 or 20 mg of ICS 205-930 or placebo were infused i.v. in a random double-blind fashion. Gastric emptying and antral motor activity were studied scintigraphically. 4. Gastric emptying was not altered after 10 mg but slower after 20 mg of ICS 205-930 than after placebo. Emptying after 20 mg of ICS 205-930 was significantly slower than after 10 mg of ICS 205-930. 5. Antral contraction amplitude was slightly lower after 20 mg of ICS 205-930 than after placebo, whereas the effects of 10 mg ICS 205-930 did not differ from those of placebo. 6. The results suggest that the investigated doses of ICS 205-930 have only slight effects on gastric motor activity of healthy young men, with 20 mg reducing the rate of emptying.

The Effects of Prostaglandins on Gastric Emptying

This review summarizes the effects of prostaglandins on gastric emptying in animals and man. It appears that prostaglandin E2 (PGE2) and prostaglandin F2 alpha increase the rate of gastric emptying in animals. PGE2 increases the emptying of liquids from the human stomach; more recently developed prostaglandin analogues, however, such as misoprostil and trimoprostil, have no effect on the rate of emptying of the human stomach. The PGE1 analogue, rioprostil, increases the rate of emptying of an acid load from the stomach; it does not, however, affect gastric emptying of a meal consisting of meat broth and glucose. It is concluded that prostaglandins do not affect the rate of gastric emptying of solids, but that some of these compounds do increase gastric emptying of liquids in both animals and man.

Gastric emptying of ordinary food: effect of antrum on particle size.

The lack of reliably quantitative methods has delayed understanding how the stomach empties and processes foods. Rapid refinement of gamma cameras has prompted the development of several methods for labeling of ordinary foods with radionuclides. These methods allow rapid labeling with tightly adherent nuclides and are safe for studies both in animals and humans. Nuclide-labeled foods have also permitted detailed analyses of gastric emptying in animals prepared with chronic duodenal fistulas. Early results indicate that the stomach retains foods until these are fragmented into particles smaller than 0.5 mm in diameter, and that this sieving is achieved in the antral region of the stomach. The speed of fragmentation of foods into particles of this size as well as the speed of emptying appear to be closely regulated by chemoceptive mechanisms in the small intestine, which can inhibit these processes. Thus, chemical composition of the meal regulates gastric emptying as well as the physical nature of the food, which determines how easily it can be fragmented by the stomach.

Effects of Antacids on Gastric Emptying

Aluminum hydroxide gel delays gastric emptying in rats and man. This effect of aluminum hydroxide gel varies with the concentration of aluminum in solution in the stomach when pH, osmolarity, and anion content are held constant. Because aluminum solubility drops as pH is raised, those antacids which neutralize more effectively than aluminum hydroxide gel alone and which contain "nonreactive" aluminum hydroxide result in lower aluminum concentration and do not affect the rate of gastric emptying in animals or in man. By using [51Cr]sodium chromate and a gamma camera technique, half-emptying time in 6 subjects with no gastrointestinal disease was shown to be prolonged from 13.1 min after water ingestion to 48.0 min after three hourly doses of aluminum hydroxide gel. Conventional nonabsorbable markers, including phenol red, were found to be of limited use for studying gastrointestinal function in the presence of antacid gels, most of which adsorb dyes.