Effect of meal volume and energy density on the gastric emptying of carbohydrates.

Gastric test meals of Polycose, with volumes of 300, 400, and 600 ml and energy densities of 0.5, 0.7, 1.0, 1.3, 1.5, and 2.0 kcal/ml, were given to 21 men and recovered after 30, 60, or 120 min. Polycose, a polymer of glucose, was chosen as a soluble homolog of food. The results of 1134 Polycose meals were analyzed in terms of the rates of energy delivery to the duodenum. The rates of emptying in the initial 30 min were significantly greater than in either the 30-60- or 60-120-min periods. Increases in either energy density or meal volume increased the rate of energy delivery in all time periods (p less than 0.001). The steady rate of energy delivery, which was evident after the initial 30 min, was correlated with increases in the initial meal volume and energy density, such that doubling the volume of meals from 300 to 600 ml increased the rate of emptying by a mean of 0.72 kcal/min, whereas doubling the energy density of the meals from 0.7 to 1.3 kcal/ml raised the rate of emptying by 0.62 kcal/min, with an overall mean rate of caloric emptying of 2.5 kcal/min. Thus, increases in either the initial volumes or the energy densities of the test meals significantly increased the rate of acceptance of energy by the duodenum.

Intrinsic emptying pattern of the human stomach.

Twenty-three subjects were given a total of 336 meals of 750 ml saline that was recovered at 5, 10, and 20 min to determine the intrinsic gastric emptying pattern. Minimal slowing of gastric emptying by duodenal receptors resulted from 120 mM NaCl. Analysis of the residuals from the within-subject regressions for every subject's remaining volume vs. time showed that the exponential model of gastric emptying most appropriately described the data when the volume instilled at time 0 was included.

Effect of synthetic prostaglandin E1 analog on aspirin-induced gastric bleeding and secretion.

Twelve healthy subjects were given aspirin (975 mg four times a day) for four days. On days three and four, each dose of aspirin was preceded by a synthetic protaglandin E1 analog (misoprostol, Searle) either 25 micrograms, 50 micrograms, or placebo in a double-blind balanced full crossover design. Bleeding, gastric secretion of acid and chloride, and accumulation of gastric luminal DNA and calcium as indices of cell shedding and mucus secretion were measured by three daily morning gastric washouts, corrected for gastric emptying. Both bleeding and gastric secretion were greater on day 4 with aspirin and placebo than on day 0. With 50 micrograms misoprostol, and to a lesser extent with 25 micrograms, bleeding and gastric secretion were reduced on day 4 compared to day 4 with placebo or aspirin only days. The reduction in gastric bleeding with the 50-microgram dosage of misoprostol was directly related to the reduction in acid secretion. The ratios of changes in acid and chloride outputs did not indicate any increase in bicarbonate secretion. No changes in the recoveries of calcium or DNA were seen.

The relation between freely chosen meals and body habitus.

By bomb calorimetry, we conducted a 7-day study of the energy contents of the freely chosen meals of 11 male subjects under their ordinary living conditions. Their body weights ranged from 60 to 99 kg and Quetelet indices ranged from 211 to 271 X 10(-5). Despite the wide range of body weight, there was no relation between daily energy intake and body weight, height, or Quetelet index. However the thickset subjects took diets and meals with higher energy density than the lean subjects (p less than 0.05 one-tailed for diets, p less than 0.025 one-tailed for meals). On average, the energy of lunch and dinner contributed 26 and 44% of daily energy, respectively. There was a significant negative relation between the energy of lunch and that of dinner (p less than 0.01), but no significant association between weight of lunch and that of dinner (p greater than 0.1).

Relation between gastric secretion of acid and urinary excretion of calcium after oral supplements of calcium.

The object of this study was to determine in 12 healthy subjects the relation between gastric secretion of acid and absorption of calcium from two different preparations of calcium, as judged from increased outputs of calcium in the urine. The increase in urinary output of calcium after solid calcium carbonate was greater in the subjects with the most gastric secretion of acid. The absorption of calcium after a solution of monocalcium citrate was independent of gastric secretion of acid. In the four subjects with the least gastric secretion of acid, there was no absorption of calcium after calcium carbonate, but the absorption after monocalcium citrate was as great as that for those who secreted greater amounts of acid.

The effect of dietary sodium and protein on urine volume and water intake.

To test the notion that water intake and urine volume are related to dietary sodium or protein intake in free-living persons, we studied normal men at three levels of sodium intake and two levels of protein intake. Twenty-four men received 10, 200, and 400 mEq/day sodium intake for 7 days while protein and caloric intake were maintained constant. Eight men received 80 or 180 gm/day protein intake for 7 days while caloric and sodium intake were maintained constant. Although sodium, solute, and urea nitrogen excretion changed appropriately according to the regimens, there was no demonstrable influence of sodium or protein intake on water intake and urine volume. We conclude that in normal free-living American man, water consumption is independent of either sodium or protein intake.

Gastric bleeding and gastric secretion with sulindac and naproxen.

We have examined concurrent gastric secretory rates and bleeding by a gastric wash technique during treatment with naproxen, sulindac, and placebo. Twelve subjects, in each of 4 treatment periods, took either placebo, sulindac 200 mg, naproxen 250 mg, or naproxen 375 mg, twice a day for four days. Of the resultant 192 days (12 subjects, 4 drugs, 4 days/drug), two thirds of all days showed bleeding at a rate less than 0.5 ml/day; this low rate of bleeding was seen with all treatments. In spite of this minor bleeding, we were able to show statistically significantly less bleeding with placebo than with drugs; placebo never resulted in a maximum rate of bleeding for any subject. Distinctions between drugs on the basis of bleeding, however, were not possible. Correlations between outputs of acid and chloride were not significantly affected by any of these drugs. In contrast to previous results with aspirin, no correlation between rates of bleeding and gastric secretion could be established. The low water solubility of these drugs at the pH of gastric contents may account for their causing very little bleeding. In effect, the greater the gastric secretion of acid the less the absorption through the gastric mucosa.

Mechanisms and disorders of gastric emptying.

The stomach converts food into fragments and then liquifies it before emptying it into the duodenum. Gastric emptying of liquid foodstuffs is so controlled that about 200 kcal/hr are delivered to the duodenum. The volume of the meal, its energy density (kcal/ml), and the proportions of fat, carbohydrate, and protein in the meal have minor effects on the rate of gastric emptying of energy. Regulation is achieved through the osmotic effect and calcium binding of the products of digestion in the duodenum. There are no receptors that respond to energy.

Does calcium mediate slowing of gastric emptying by fat in humans?

The relative potencies of 47 compounds in slowing gastric emptying in one subject are given. The majority of the most effective compounds are detergent, but all detergents do not slow gastric emptying. It is proposed that the property common to those detergents that slow gastric emptying is the binding of ionized calcium. Disodium edetate (EDTA) is not a detergent. It has a high affinity for calcium, and it slows gastric emptying strongly. Reasons are given for proposing that decreasing the volumes of the lateral intercellular spaces of the luminal half of the duodenal villi mediates the slowing of gastric emptying by carbohydrate, protein, fats, and acids. Osmotic stimuli in the duodenal lumen, or in the enterocytes, reduce the flux of water into the lateral intercellular spaces. Anions of fatty acids and hydrogen ions displace calcium from a site on the tight junctions at the luminal border of the enterocytes. As a result, the tight junctions become more permeant to water and the lateral intercellular spaces shrink as their content drains into the duodenal lumen. Shrinking of the lateral intercellular space is proposed as the final common event in the transduction of the duodenal stimuli that slow gastric emptying.

Does calcium mediate the slowing of gastric emptying in primates?

Disodium edetate (EDTA, 1 g/l) in test meals of water slowed gastric emptying strongly in one human and in four rhesus monkeys. When the binding sites of the EDTA were loaded with calcium before it was given in the test meal, there was little effect on gastric emptying. It is suggested that EDTA takes up calcium from the "tight junctions" of the duodenal epithelium. As a result a signal is set up that slows gastric emptying. It is postulated that the anions of fatty acids produced during the digestion of triglycerides in the duodenum also slow gastric emptying by the same mechanism. We explain how fats, carbohydrates, and proteins could all slow gastric emptying by operating on the same receptor.

Effect of prostaglandin E2 on gastric mucosal bleeding caused by aspirin.

The effect of prostaglandin E2 on gastric mucosal bleeding caused by aspirin was studied. Blood in serial gastric washings was measured chemically for 30 min. Normal blood loss was equivalent to 0.05 ml/day. Aspirin, 600 mg four times daily, increased gastric bleeding on day 1; bleeding was further increased on day 2. On day 2, ingestion of 0.5 mg of prostaglandin E2 15 min before 600 mg of aspirin reduced the gastric microbleeding caused by aspirin. Prostaglandin E2, 0.5 mg four times daily, did not change the normal blood loss. No consistent changes in gastric emptying or in secretion of chloride were detected.

The gastric emptying of small volumes given in quick succession.

1. Ten subjects were given solutions of 33 mM-trisodium citrate or 505 mM-glucose, by tube into the stomach; either 25, 50, 100 or 200 ml. were instilled. The gastric contents were recovered, after 3 min with the trisodium citrate solution and after 10 min with the solution of glucose, then the stomach was washed out with 250 ml. water. Each volume was instilled six times in quick succession on one day with the trisodium citrate solution, and four times on another day with the solution of glucose. The recovered volume of the original meal, which contained Phenol Red, was assessed from the amount of dye in the combined recovery and wash. Each day's procedure was replicated on three days. 2. About half of the trisodium citrate solution was recovered after 3 min and about half the solution of glucose after 10 min, independent of the volume instilled. 3. Glucose slowed gastric emptying. The effect was seen when amounts as low as 1.5 g passed into the duodenum in 10 min. 4. Within-subject, the volumes of trisodium citrate (a distending gastric stimulus) recovered at 3 min allowed predictions of the volumes of glucose solution (a gastric distending and a duodenal osmotic stimulus) recovered at 10 min. 5. The volumes recovered on one day fell progressively with successive instillations of 25, 50 and 100 ml. 6. The results showed that the control system governing gastric emptying responded to volume and osmotic stimuli even when the intragastric volumes were as small as those in the stomach during the interdigestive periods.

A possible relation between the regulation of gastric emptying and food intake.

The greater the concentration of energy (kcal/ml) in the gastric contents, the less is the volume rate of transfer per minute to the duodenum. Two sets of duodenal receptors are involved, one stimulated by the osmotic properties of the digestion products of carbohydrate and protein and one by the digestion products of fat. All three food stuffs slow gastric emptying equally when their concentration is expressed as kilocalories per mililiter. Doubling the energy density of food from 0.7 to 1.4 kcal/ml increased the transfer from 116 to 176 kcal/30 min (50% instead of to 232 kcal/30 min had there been no slowing of gastric emptying. Changing the energy density of formula feedings given to infants from 0.7 to 1.4 kcal/ml increased their food intake by 50%. A tendency to choose diets with a high energy density is characteristic of persons with relatively high weight-to-height ratio. It seems possible that the regulation of gastric emptying and the control of food intake have components in common and that rapid gastroduodenal transfer of energy may be associated with high food intake.

Does lying on the right side increase the rate of gastric emptying?

1. Saline test meals (750 ml., 125 mM-NaCl) were given by tube into the stomachs of five subjects who were either sitting, lying on the left side, or lying on the right side. The gastric contents were recovered at 10 min. The rate of gastric emptying was assessed from the recovery of the original solution, marked with phenol red. 2. The mean volume of this rapidly emptying test solution recovered after 10 min was 215 ml. from subjects lying on the right side and 431 ml. from subjects lying on the left side (P < 0.005) and 308 ml. from the sitting subjects. 3. Similar studies were made with 750 ml. test meals of a solution of glucose monohydrate (100 g/l.) given to the same subjects in the same positions, but the recoveries of this more slowly emptying solution were made at 20 min. 4. There was no statistically significant difference between the volumes recovered when subjects lay on their left sides (589 ml), when they lay on their right sides (555 ml.), and when they were sitting (564 ml.). 5. These results are consistent with posture influencing gastric emptying provided the given meal does not strongly activate duodenal receptors mediating the slowing of gastric emptying.

Aspirin-induced gastric bleeding stops despite rising plasma salicylate.

In 7 subjects, 100-ml successive portions of buffered acid (pH between 3.5 and 2.9) solutions of aspirin (1 g/liter) were instilled into the stomach and recovered after 10 min. Blood in the recoveries was estimated chemically. After there had been three successive increases in the rate of blood loss into the gastric lumen, typically rising from about 0.1 to 1 ml/day after about 80 min, buffered neutral solution of aspirin was instilled and recovered after 10 min. This was followed by a fall in the rate of blood loss into the gastric lumen which occurred despite a rise in the concentration of salicylate in the plasma from a mean of 55 mg/liter to 74 mg/liter. Under these conditions, salicylate in the plasma and acetylsalicylate in the gastric contents did not prevent gastric mucosal bleeding from falling to control levels within 50 min.

A procedure for measuring gastric bleeding caused by drugs.

Seven subjects were given one day's treatment with full doses of either aspirin, ibuprofen, or placebo, and then their stomachs were washed out three times at intervals of 10 min, for five successive days. The blood in the recoveries was estimated chemically. After compensating for gastric emptying, the rate of bleeding was expressed as ml blood per day. Relative to placebo, one day's treatment with aspirin increased the rate of blood loss significantly at day 1, median 2.7 ml/day, and not thereafter. A corresponding dose of ibuprofen did not produce any significant bleeding. The procedure gives specific information about gastric bleeding. It can measure rates of bleeding down to 0.01 ml/day.

Scanning esophageal impedance probe for measurement of luminal cross section.

A scanning esophageal probe for measuring luminal cross section is described. Current is injected into electrode assemblies so that a variable voltage output directly proportional to interelectrode impedance and inversely proportional to cross-sectional area of the medium around the electrodes may be measured. The device is capable of measuring the cross section of glass cylinders. It was used in one esophagus to measure the cross-sectional area of different sizes of swallowed bolus. The probe offers a safe and repeatable method of studying dynamic changes in luminal dimensions of the esophagus.

Energy density of food, gastric emptying, and obesity.

Certain receptors in the duodenal mucosa respond to the osomotic effects of the digestion products of dietary carbohydrates and proteins with a resultant slowing of gastric emptying. Other receptors respond to the soaps formed during the digestion of fats. The relative effectiveness of these two sets of receptors is such that foods with equal energy produce equal slowing of gastric emptying. Thus the rate of delivery of energy to the duodenum, and hence to the blood, can be regulated without the energy having been directly measured. The results in the literature that we have examined are consistent with this duodenal system playing some part in the regulation of food intake.

Glucose, glycine and diglycine in test meals at stimuli to a duodenal osmoreceptor slowing gastric emptying.

1. Five subjects took 210 test meals of 750 ml. water containing 30--300 m-molal glucose or glycine, or 15--150 m-molal diglycine, or plain water. 2. The greater the concentration of solute, the greater was the volume of original meal recovered from the stomach after a fixed time. 3. On a molal basis glucose was half as effective as diglycine in slowing gastric emptying. This was consistent with the osmoreceptor being exposed to the diglycine after it had been split by the hydrolase of the cytosol of enterocytes (the absorbing cells of the small intestine). 4. The slowing of gastric emptying (ml./mole.1.) was about 10% greater for glycine than it was for glucose. There was apparently a threshold concentration below which glycine did not slow gastric emptying. 5. It was proposed that the response of the doudenal osmoreceptor might depend upon shrinking and swelling of the lateral intercellular space around the enterocytes.

Relation between volume swallowed and velocity of the bolus ejected from the pharynx into the esophagus.

The velocity of the front face of a liquid saline bolus ejected from the pharynx into the esophagus was measured by recording changes of luminal electrical impedance with three sets of electrodes in 9 subjects. At a site 26 cm from the incisors, the mean velocity of the front face of the bolus increased from 10 to 70 cm sec-1 as the volume swallowed was raised from 5 to 30 ml. The velocity of the front face of the bolus was greater 26 cm from the incisors than it was 32 cm from the incisors.