Studies of the effect of metoclopramide and apomorphine on gastric emptying and secretion in man

With oral and intravenous doses of metoclopramide there was no constant effect on the gastric emptying of test meals of glucose or sodium citrate, nor was secretion of acid by the stomach in response to test meals of glucose or sodium citrate affected. Apomorphine, in subnauseous doses (0.25 mg intravenously) slowed the gastric emptying of test meals containing sodium citrate, and 10 mg of intravenous metoclopramide abolished the slowing of gastric emptying caused by apomorphine.     

Different gastric,pancreatic, and biliary responses to solid-liquid or homogenized meals

We have compared responses to an ordinary solid-liquid (S) meal and to a homogenized (H) meal of identical composition (sirloin steak, bread, butter, ice cream with chocolate syrup, and water) by measuring simultaneously postprandial gastric, pancreatic, and biliary functions by marker-perfusion techniques. Responses to each (S or H) meals differed strikingly both in magnitude and pattern. S meals elicited a stronger early gastric secretory response (acid, pepsin, and volume) which compensated for faster initial emptying and resulted in higher gastric acidity and volume than after H meals. Further, nutrients ingested with S meals were emptied at a slower rate than H (as evidenced by a more gradual decline in intragastric buffer and osmolality, as well as time required for complete emptying of the meal). This, in turn, prolonged pancreatic and biliary responses since stimulation of these organs continued for as long as meal was delivered into the duodenum. However, early biliary outputs (gallbladder response) were less after S than H, probably because nutrients entered the duodenum more slowly and were initially diluted by rapidly emptying water. The physical characteristics of each meal (encompassing appearance, taste, and form of ingestion) probably accounted for early differences in digestive responses. Later, interactions between gastric (motor and secretory), pancreatic, and biliary functions played a major role. Our findings suggest that gastric, pancreatic, and biliary responses to liquid test meals introduced into the stomach may differ substantially from the presumably more physiological response to ordinary solid-liquid meals.Dr. Summerskill died March 9, 1977.This investigation was supported in part by Research Grant AM 6908 from National Institutes of Health.     

Gastric emptying of oil from solid and liquid meals

Digestion of fat in pancreatic insufficiency (PI) is strongly affected by how rapidly fat enters the duodenum. We postulated that: (1) oil empties faster in PI than in normals and (2) in both, it empties in a load-dependent fashion. We used a gamma camera to test these ideas by comparing gastric emptying of iodine-123 iodinated oil in normal and pancreatic-insufficient subjects after 15 g of free oil were ingested in a small spaghetti meal and 60 g of oil were ingested in a large spaghetti meal and in a milk emulsion. Indium-113m marked gastric emptying of water in the milk. In both groups after all meals, oil emptied fastest initially, slowing later; and oil emptied three to four times faster when 60 g vs 15 g were ingested. There were no significant differences between the groups of subjects with respect to gastric emptying of the spaghetti meals, but the pancreatic-insufficient subjects emptied both oil and water faster from the milk emulsion than did the normal subjects. The slower emptying of oil in the normal subjects was associated with significantly more layering of oil to the top of the intragastric milk emulsion.     

Antroduodenal motor response to solid-liquid and homogenized meals.

The effect of the physical state of food on antroduodenal motor activity and the pattern of the emptying of an aqueous phase marker were examined in 6 healthy volunteers using an intestinal perfusion technique and intraluminal pressure transducers. Ingestion of a solid-liquid meal produced marked phasic changes in pressure in the distal antrum, lasting 92 +/- 10 min (mean +/- SE), while, in contrast, ingestion of the same nutrients in a homogenized state resulted in complete absence of distal antral changes in pressure lasting 133 +/- 12 min. The motor responses of the proximal antrum and duodenum were similar for the two meals. Both meals emptied during a 3-hr period, the pattern of emptying of the aqueous phase marker being similar for the two meals except for the first 40 min, when emptying was more rapid after the solid-liquid meal. The homogenized meal emptied despite the absence of changes in distal antral pressure. The gastrin response was similar for the two meals and is therefore not responsible for the different patterns of antral motility and gastric emptying.     

Gastric emptying of lactose and milk in subjects with lactose malabsorption

Six lactose absorbers (LA) and 5 lactose malabsorbers (LM) had tests of gastric emptying with 750-ml meals of glucose in water, lactose in water, plain milk, and chocolate milk. The glucose and lactose meals emptied in a similar fashion in LA and LM subjects with a significant decrease in gastric emptying as the osmolarity of the meals was doubled. If the data are normalized by dividing lactose emptying by the emptying of glucose meals of twice the osmolality in each individual, the lactose malabsorbers empty significantly more lactose. Both LA and LM subjects emptied comparable amounts of milk meals having similar osmolarity. Chocolate milk, which had a higher osmolality than plain milk, emptied more slowly than plain milk in both groups, and this difference was significant in the LM group.     

Gastric emptying and intestinal transit of hyperosmolar solutions in relation to indomethacin and certain gut polypeptides in the rat

The present study in the rat demonstrates an inhibitory mechanism of gastric emptying, sensitive to the osmolality of a liquid meal. Gastric emptying and intestinal transit were studied in groups that differed with regard to the osmolality of the gastric or duodenal instillation, experimental time, and indomethacin treatment. By intragastric instillation animals were fed an aqueous solution containing the nonabsorbable marker 51CrO2-4. After certain fixed time intervals the rats were killed and the stomach and small intestine were dissected out en bloc. The distribution of the isotope along the gastrointestinal canal was then determined. Intestinal transit was evaluated in a similar manner. The marker solution was introduced into the duodenum. A hyperosmolar solution, 1200 mOsm kg-1, was emptied from the stomach significantly more slowly than was an iso-osmolar solution, 300 mOsm kg-1. Of the iso- and hyper-osmolar solutions 87% and 74%, respectively, were emptied in 1 h. The isotope distribution along the intestinal canal after intraduodenal instillation was not affected by the osmolality of the installation. The osmotic inhibition of gastric emptying was not affected by indomethacin treatment (4 mg kg-1) or related to elevated plasma levels of gastrin, neurotensin, somatostatin, or gastric inhibitory polypeptide.     

Effects of meal composition on gallbladder and gastric emptying in man

Cholecystogastric scintigraphy, utilizing [^99mTc]HlDA to label the gallbladder contents and [¹¹¹In]DTPA to label different meals, was utilized to determine the relationships between gallbladder and gastric emptying after meals of differing composition. Gallbladder emptying was determined in response to a multicomponent meal and to monocomponent fat, carbohydrate, and protein meals and in response to isotonic and hypertonic dextrose and isotonic and hypertonic saline. Also, the gallbladder emptying responses to equivalent multicomponent solid and liquid meals were compared. Significant gallbladder emptying was observed in response to the multicomponent meal and the monocomponent fat, carbohydrate, and protein meals. The most rapid and complete gallbladder emptying was seen with the multicomponent meal and the monocomponent fat meal. Significant gallbladder emptying was stimulated, not only by isotonic and hypertonic dextrose, but also by hypertonic saline. The gallbladder emptied more rapidly after a liquid than after a solid meal.     

Influence of meal weight and caloric content on gastric emptying of meals in man

This study was designed to assess the relative influence of meal weight and caloric content on gastric emptying of liquid and solid meals in man. A dual radioisotopic method which permits noninvasive and simultaneous measurement of liquid-and solid-phase emptying by external gamma camera techniques was employed. Nine healthy volunteer subjects ingested 50-,300-, and 900-g lettuce and water meals adjusted to either 68, 208, or 633 kcal with added salad oil. The following observations were made: (1) absolute emptying rates (grams of solid food emptied from the stomach per minute) increased directly and significantly with meal weight; (2) increasing meal total caloric content significantly slowed solid food gastric emptying but did not overcome the enhancing effect of meal weight; and (3) liquid emptying rates were uninfluenced by meal total kcal amount.The authors wish to express their appreciation to the Salt Lake Veterans Medical Center, Medical Research Service for their support.     

Progression of changes in gastric emptying of hypertonic liquids after proximal gastric vagotomy

Gastric emptying rates of hypertonic (10%) dextrose liquid meals were studied in five dogs before, and 3, 6, and 12 months after proximal gastric vagotomy (PGV) without drainage. The purpose of this study was to determine if operation-related changes in emptying rates normalized or became more disparate during the year after PGV. An increased rate of emptying during the first 5 min after ingestion was seen at 3 months after PGV, which significantly increased (P<0.025) after 6 and 12 months. The remainder of the meal after PGV emptied at a regulated exponential rate unchanged throughout the postoperative year from its preoperative rate. Total volumes of gastric aspirate at four intervals after meal ingestion did not significantly change across the four test periods in respect to endogenous secretion or pH acidity.Supported by The Veterans Administration.     

Effect of vagotomy on gastric emptying

To determine whether pyloroplasty or a disrupted osmoreceptor mechanism is primarily responsible for the increased gastric emptying of hypertonic sugar solutions after vagotomy and pyloroplasty, test meals of 10% glucose (556 mOsm/kg) and NaCl (200 mOsm/kg) were administered to duodenal ulcer patients with no prior operation, after vagotomy and pyloroplasty, and in patients with prior vagotomy, hiatal herniorrhaphy, and no pyloroplasty. Hypertonic glucose meals were emptied more rapidly than normal after both operations. The hypotonic NaCl meal was emptied no faster postoperatively than it was preoperatively. The results rule out pyloroplasty as the primary factor responsible for the observed increased rate of gastric emptying. Instead, the data suggest that the osmoreceptor mechanism described by Hunt is disrupted by vagotomy.Presented in part at the Midwestern Section. American Federation for Clinical Research, Chicago, Ill. Nov 1, 1969.Supported by Veterans Administration Part II Research Funds.     

Gastric emptying after roux-y and billroth-I gastrectomy depends on viscosity of meal and contractile patterns of small intestine in dogs

The aim of the study was to examine gastrointestinal motility after distal gastrectomy and the influence of meal viscosity on gastric emptying. Gastrointestinal motility and gastric emptying of acaloric meals with different viscosities were measured in normal dogs and after a two-thirds gastrectomy with Billroth-I or Roux-Y gastroenterostomy. After distal gastrectomy, gastric emptying depended on the viscosity of the meal, as in normal dogs. Acaloric viscous meals emptied significantly faster in the Billroth-I than in the Roux-Y group due to different contractile patterns of the duodenum and jejunum. In comparison to normal dogs, gastric emptying of viscous meals was accelerated in the Billroth-I and delayed in the Roux-Y group. Several motility parameters of the stomach and intestine differed between the normal and gastrectomized dogs. Thus, after distal gastrectomy, the viscosity of the meal and the contractile patterns of the small intestine are important determinants of gastric emptying.Studies were supported by the Deutsche Forschungsgemeinschaft, grant Eh 64/3-1.     

Gastric emptying of liquids in normal subjects and patients with healed duodenal ulcer disease

We have characterized the dose-response of inhibition of gastric emptying by acid, glucose, and fat in duodenal ulcer (DU) patients and normals (N) matched by age and sex. Gastric emptying was measured by the George technique while intragastric pH was maintained constant by intragastric titration. Acid, glucose, and fat inhibited gastric emptying in a dose-dependent fashion in both groups. DU patients emptied all three types of meals faster than normals, but differences were only seen at the lower doses of glucose or with the less potent doses of acid and fat. With low concentrations of glucose and at all concentrations of acid, DU patients emptied the meals faster than normals only in the first 5 min; but with fat the differences persisted throughout the 30-min test. Differences in gastric emptying of liquid meals in DU patients vs normals are small, and they occur with nutrient as well as acid meals. The variable responses obtained with the different concentrations may explain the inconsistencies found by other workers.     

Effect of composition of gastric contents on resistance to emptying of liquids from stomach in humans

Experiments were conducted in normal healthy volunteers to investigate whether factors other than the intragastric pressure induced by tonic contraction of the gastric fundus could regulate the gastric emptying of liquids. The emptying of solutions of different osmolality and composition from the stomach was measured, while maintaining the intragastric pressure constant with a barostat system that employed an external reservoir. Preliminary experiments showed a linear relationship between intragastric pressure and emptying rate, but indicated that a normal intragastric pressure of 7 cm water would be insufficient by itself to maintain normal emptying. When intragastric pressure was maintained at 20 cm water, an isotonic solution of 30 mM glucose in saline (278 mosm/kg) emptied at a rate of 49.9±0.5 ml/min (mean± sem,N=11. Milk (284 mosm/kg) and a hyperosmolar solution of 30 mM glucose in saline (586 mosm/kg) significantly reduced the emptying rate. These results suggest that factors other than the intragastric pressure induced by fundic contraction regulate the rate at which liquids empty from the stomach and that the slower emptying of hyperosmotic solutions or solutions containing fat could be brought about in part either by an increased resistance of the pylorus and possibly the duodenum or a reduction in the effectiveness of an antroduodenal pump.This work was supported by grant 51 17903 from the University of Sheffield, Sheffield, U.K.     

Regulation of gastric emptying by ileal nutrients in humans

Studies were carried out in 25 healthy male volunteers to investigate the effect of ileal infusion of solutions of different nutrient composition and osmolality on the profiles of a radiolabeled solid meal emptying from the stomach. Ileal infusion of a 50% corn oil emulsion or a 20% oleic acid emulsion slowed the rate of gastric emptying compared with ileal infusion of isotonic saline (0.9%). In contrast, infusion of either hypertonic saline (430 mosmol), distilled water, or isotonic solutions containing protein hydrolysate (8 g%) or glucose (50 mM) had no effect on the gastric emptying profile. These experiments support the hypothesis that the presence of unabsorbed lipid or fatty acids in the distal small intestine may delay gastric emptying, but suggest that sugars and proteins are ineffective. As infusion of both protein hydrolysates and lipid into the ileum can delay small bowel transit in humans, the data suggest that ileal regulation of gastric emptying and small bowel transit may be mediated by different mechanisms.     

Relationship of the motor activity of the antrum, pylorus, and duodenum to gastric emptying of a solid-liquid mixed meal

The postprandial motor activity of the antrum, pylorus, and duodenum in 15 healthy volunteers was compared with the profiles of emptying of the solid and liquid components of a meal. The liquid component of the meal emptied rapidly in an exponential manner, whereas the solid remained in the fundus of the stomach until approximately 80% of the liquid had emptied and then emptied in a linear manner. The onset of solid emptying was associated with an increase in the rate of occurrence of antral pressure waves (p less than 0.05), and the half-time for solid emptying (t1/2 - lag period) was inversely correlated (p less than 0.05) with the rate of coordinated contractions involving the antrum. The substitution of 25% dextrose in normal saline as the liquid component of the meal increased the half-time for liquid emptying from a median of 8 to 40 min (p less than 0.01), increased the lag period for solid emptying from 40 to 87 min (p less than 0.01), and increased the rate of occurrence of isolated pyloric pressure waves during the solid lag phase from 7 to 58/h (p less than 0.05), but did not affect the slope of solid emptying or the rate of coordinated contractions involving the antrum during the solid emptying period.     

Effect of size and density on canine gastric emptying of nondigestible solids

Previous studies suggested that the food-containing canine stomach retains large, nondigestible spheres until all food has emptied; but it is not known whether there is a threshold size or a gradation of sizes that will empty along with food. Further, nothing is known of the effects of such parameters as density, shape, and surface energy on the emptying of nondigestible particles of any given size. To answer these questions 6 dogs with chronic duodenal fistulas were studied. Radiolabeled food and spheres were collected from the fistulas to compare the rate of gastric emptying of the spheres with that of the food. After a standard test meal of 99mTc-labeled liver, steak, and water, diverted chyme was collected over a stack of sieves in 30-min fractions over 5 postcibal hours. The percent of fed spheres and fed 99mTc-labeled liver in each collection was counted, and liquid chyme was returned to the distal duodenum. Spheres with a density of 1 emptied progressively faster as sphere diameters were decreased from 5 to 1 mm; but 0.015-mm spheres emptied at about the same rate as those with diameters of 1 mm. Emptying of the spheres became similar to emptying of the 99mTc-labeled liver at about 1.6 mm. Spheres with densities less than 1 or greater than 1 emptied more slowly than spheres of the same size with a density of 1, whereas paper squares emptied the same way as spheres of comparable size and density. Surface energy did not affect emptying. The findings indicated that both sphere size and density affect their emptying in the presence of food.     

Effects of nutrients on gastrointestinal motility and gastric emptying after Billroth-I gastrectomy in dogs

We wanted to clarify the way in which nutrients influence gastrointestinal motility and gastric emptying following distal gastrectomy with Billroth-I gastroduodenostomy. Four gastrectomized dogs were equipped with extraluminal strain gauge transducers. Gastric emptying was measured radiographically. Four intact dogs were used as controls for emptying studies. Following gastrectomy, gastric emptying of both acaloric and nutrient meals was rapid in the initial period of the experiments. Gastric outflow was supported by propagating duodenal contractions. Compared with control dogs, the early emptying of nutrient meals was accelerated. In the following period, nutrients markedly slowed gastric emptying compared with acaloric meals due to a segmenting contractile pattern of the duodenum and a significant diminution of gastrointestinal motility. Results suggest that after Billroth-I gastrectomy (1) the control of gastric emptying by nutrients acts too late to slow the initial enhanced gastric outflow, and (2) the duodenal contractile patterns influence gastric emptying.The study was supported by the Deutsche Forschungsgemeinschaft, grant Eh 64/3-1.     

Ileal lesions in Behçet's disease originate in Peyer's patches: Findings on magnifying endoscopy

The possible influence of moderate amounts of acetylsalicylic acid (ASA) on gastric emptying, duodeno-gastric reflux and small bowel propulsion was studied in rats with permanent gastric and duodenal tubes. The ASA-containing or the control solution was introduced intra-gastrically half an hour before the simultaneous administration of differently labelled radioactive test meals into the stomach and the duodenum. ASA was given as 7.5 or 15.0 mM solution in 100 mM hydrochloric acid or in 100 mM sodium chloride. After 15 minutes the gastrointestinal propulsion was examined. No effect of the ASA treatment was noted. No increase in duodeno-gastric reflux was found in the ASA-treated animals.     

Intraduodenal instillation of acid and hyperosmolal solution suppresses pentagastrin-stimulated acid secretion but not histamine mobilization in the rat stomach

In chronic gastric fistula rats provided with a duodenal loop anastomosed to the jejunum (Roux-en-Y), maximal stimulation of acid secretion by continuous intravenous infusion of pentagastrin produced a 15-fold increase of gastric histidine decarboxylase activity. Intraduodenal instillation of 0.20 M HCl or 1200 mOsm X kg-1 solution of polyethylene glycol (PEG) inhibited the maximal acid response to pentagastrin by 61% and hyperosmolal (1200 mOsm X kg-1 of PEG solution) 0.20 M HCl by 79% but did not suppress the pentagastrin-induced increase in enzyme activity. Hence, instillation of HCl and/or hyperosmolal PEG solution in the duodenum depresses the responsiveness of the parietal cells to pentagastrin without interfering with pentagastrin-induced activation of gastric histamine formation.     

Cholinergic influence on duodenal bicarbonate response to hydrochloric acid perfusion in the conscious rat

Present information suggests that endogenous prostaglandins, hormonal factors, and neuropeptides participate in the regulation of duodenal bicarbonate secretion in response to luminal hydrochloric acid. The purpose of this study was to examine the effects of cholinergic antagonists and agonists on basal and acid-stimulated bicarbonate secretion in the proximal duodenum of the conscious rat. The basal bicarbonate secretion, 9 mumol X cm-1 X h-1, increased to 21 +/- 3 mumol X cm-1 X h-1 after 5 min of exposure to 150 mM HCl and remained significantly elevated for more than 3.5 h. The muscarinic blocker atropine, 0.5 mg X kg-1, reduced the acid-stimulated bicarbonate response by a third, and higher doses did not increase the inhibition. The ganglionic blocker hexamethonium, 10-20 mg X kg-1, suppressed in a dose-related manner the alkaline response by maximally one half. The opioid inhibitor naloxone was also an effective inhibitor. Hexamethonium, but not atropine, inhibited the basal duodenal bicarbonate secretion, which was unaffected by graded doses of the cholinergic agonists bethanechol and carbachol. We conclude that cholinergic nicotinic activity participates in maintaining basal duodenal bicarbonate secretion in the conscious rat. The bicarbonate response to luminal 150 mM HCl is partially dependent on cholinergic sites, but activation of such sites is not a single final step, since cholinergic agonists failed to elevate bicarbonate secretion from basal.