Gastric emptying after truncal vagotomy and pyloroplasty

We have studied the gastric (fundic and antral) emptying of solids and liquids by a radionuclide method in 20 patients after truncal vagotomy and pyloroplasty (TVP) and in 10 control subjects. Gastric emptying of solids in TVP patients was similar to that of the control group (NS), but fundic emptying did not show a lag phase and was significantly faster. A significantly higher percentage of the solid fraction of the test meal filled the antrum (32 +/- 16% versus 20 +/- 9%; p less than 0.05), and this quantity was constant during the study period. Gastric emptying of liquids was greatly hastened after surgery. In 22 min 50 +/- 16% had left the stomach (versus 40 +/- 14% in controls; p less than 0.001). At 90 min the amount of liquid remaining in the stomach was similar to that in the control subjects. TVP accelerates fundic emptying of solids, which are transferred to an overfilled, paretic antrum. Liquids are emptied by a bimodal pattern with a precipitous initial emptying followed by a second slower phase.     

Effect of incorporating fat into a liquid test meal on the relation between intragastric distribution and gastric emptying in human volunteers.

The relation between gastric emptying and the intragastric distribution of 300 ml radiolabelled beef consommé with and without 60 g margarine was investigated by performing randomised, paired gammacamera studies in seven healthy male volunteers (aged 20-22 years). The low calorie bland meal emptied rapidly from both the proximal and distal stomach after a short lag period (4-6 min), during which 24-50% of the liquid passed into the distal stomach. Addition of margarine to the liquid test meal increased the lag period (median 32 min, range 7-60 min; p less than 0.01) and decreased the slope of emptying (T1/2 lag period 88 min, 49-146 min v 15 min, 10-57 min; p less than 0.01). During the lag period there was an initial filling of the distal stomach, similar to that with the bland liquid, followed by a redistribution of between 19% and 61% (median 46%) of the distal stomach contents back into the proximal stomach. At the onset of emptying, the distal stomach filled (median 30%, range 16-34%) and during this time the proximal stomach emptied twice as fast as the whole stomach (p less than 0.05). Thereafter, the distal stomach capacity remained relatively constant while both the proximal and whole stomach emptied at similar rates. This study shows that the delay in gastric emptying of a liquid that has a high fat content is due in part to a redistribution of distal stomach contents back into the proximal stomach.     

Role of the proximal and distal stomach in mixed solid and liquid meal emptying.

The role of the proximal and distal stomach in the emptying of solids and liquids from the stomach remains unclear. We have used a dual isotope technique to quantify proximal and distal stomach emptying of a solid (100 g of 99mTc labelled liver/ground beef) liquid (either 200 ml of normal saline (eight subjects) or 25% dextrose (seven subjects) labelled with 113mIn-diethylenetriaminepenta-acetic acid) mixed meal. A manometric catheter simultaneously measured antral, pyloric, and duodenal motor activity. The liquid component dispersed rapidly throughout the stomach and emptied after a minimal lag period. The emptying of the 25% dextrose was delayed compared with the saline. This delay was associated with increased retention of the liquid in the distal stomach, a significant increase in localised phasic pyloric contractions, and a suppression of antral contractions. The solid component initially resided wholly within a proximal stomach reservoir area. Solids then redistributed from proximal to distal stomach during the emptying of liquid from the stomach. Dextrose delayed gastric emptying of solids compared with saline by increasing the solid lag period and retention in the proximal stomach. There was no significant difference between saline and dextrose meals in the distal stomach retention of solid or in the linear rate of emptying after the lag period. We conclude that, contrary to general opinion, the proximal stomach plays an important role in the control of gastric emptying of solids while the distal stomach is important in the emptying of nutrient liquids.     

Gastric emptying and its relationship to antral contractile activity.

Gastric emptying and antral contractile activity were simultaneously measured in 3 dogs with gastric and duodenal fistulas. Contractile activity was monitored by two force strain gauge transducers on the serosal surface of the antrum of 2 dogs and a single strain gauge transducer on the serosal surface of both the antrum and fundus of the 3rd dog. Both the frequency and force (motility index) of antral contractions were determined for each 1 min period. Gastric emptying and contractile activity were recorded and compared minute by minute with test meals (154 mM saline) of 60, 120, 240, and 480 ml. Although the rate of gastric emptying increased with the frequency and force of antral contractions, up to 67 ml min-1 (mean 6.9 ml min-1) were emptied without measurable antral contractile activity and 0 to 96 ml min-1 (mean 19.4 ml min-1) were emptied during maximal antral activity (minute motility index greater than 119 mm). Antral contractile activity increased with the size of the test meal and decreased expoentially with the rate of gastric emptying. Fundal contractile activity was generally absent during the test meal. These studies suggest that although the antrum has a significant role in the emptying of liquids, other undefined factors may modify its effect on gastric emptying.     

Motor mechanisms associated with slowing of the gastric emptying of a solid meal by an intraduodenal lipid infusion

The aim of this study was to define better the motor phenomena associated with the slowing of gastric emptying by a duodenal lipid infusion. Antral, pyloric and duodenal motility were recorded in 10 healthy subjects with a manometric assembly which incorporated multiple perfused side-holes and a sleeve sensor positioned astride the pylorus. The gastric emptying of a standard solid meal and the distribution of the ingesta between the proximal and distal stomach were monitored with a radionuclide technique. A triglyceride emulsion was infused into the duodenum for 45 min once 25% of the meal had emptied. The infusion caused significant slowing in the rate of gastric emptying (P less than 0.01). This slowing in gastric emptying was associated with the suppression of pressure waves in the distal antrum (P less than 0.01) and proximal duodenum (P less than 0.01), the induction of pressure waves isolated to a narrow pyloric segment (P less than 0.01), and a redistribution of ingesta from the distal to proximal stomach. These findings suggest that pressure waves isolated to the pylorus, changes in the intragastric distribution of ingested food, and changes in proximal duodenal motility may all act in concert with changes in antral motility to regulate the gastric emptying of solids.     

The Effect of Erythromycin in Gastric Emptying of Solids and Hypertonic Liquids in Healthy Subjects

We report our study of the effect of erythromycin on gastric emptying of solid and liquid meals in 10 healthy subjects. On different occasions, subjects consumed either a radiolabeled 50% glucose solution, or a radiolabeled standard solid meal after placebo, and after receiving 200 mg of erythromycin intravenously. Erythromycin accelerated the gastric emptying of the hypertonic liquid meal by significantly decreasing the duration of lag phase ( p < 0.0001), by significantly increasing the emptying rate at the postlag period ( p < 0.001), and by significantly decreasing the duration of the postlag period ( p < 0.0001) and the meal remaining in the stomach at 15 ( p < 0.05), 30 ( p < 0.001), and 60 ( p < 0.01) min postprandially. In addition, erythromycin administration induced a significant plasma fall at 15 ( p < 0.05) and 30 ( p < 0.01) min and a significant increase in pulse rate at 15 and 30 min ( p < 0.01) after consumption of the hypertonic glucose solution, whereas three subjects experienced symptoms suggesting dumping syndrome. Furthermore, erythromycin administration enhanced the gastric emptying of solids by almost abolishing the duration of lag phase ( p < 0.0001) and by reducing the overall t_1/2 of emptying ( p < 0.0001), whereas less food was retained in the stomach at 60 ( p < 0.001) and 120 ( p < 0.0001) min postprandially. Conversely, the postlag t_1/2 of the solid meal emptying was not affected by erythromycin, as compared to placebo. We conclude that erythromycin has gastrokinetic properties, affecting the gastric emptying of both liquids and solids.     

Hyperglycaemia slows gastric emptying in Type 1 (insulin-dependent) diabetes mellitus

Summary In 10 patients with Type 1 (insulin-dependent) diabetes mellitus gastric emptying of a digestible solid and liquid meal was measured during euglycaemia (blood glucose concentration 4–8 mmol/l) and during hyperglycaemia (blood glucose concentration 16–20 mmol/l). Gastric emptying was studied with a scintigraphic technique and blood glucose concentrations were stabilised using a modified glucose clamp. Patients were also evaluated for gastrointestinal symptoms, autonomic nerve function and glycaemic control. When compared to euglycaemia, the duration of the lag phase before any of the solid meal emptied from the stomach (p = 0.032), the percentage of the solid meal remaining in the stomach at 100 min (p = 0.032) and the 50% emptying time for the solid meal (p = 0.032) increased during hyperglycaemia. The 50% emptying time for the liquid meal (p = 0.042) was also prolonged during the period of hyperglycaemia. These results demonstrate that the rate of gastric emptying in Type 1 diabetes is affected by the blood glucose concentration.     

Gastric and oesophageal emptying in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 20 randomly selected Type 2 (non-insulin-dependent) diabetic patients receiving oral hypoglycaemic therapy and 20 control subjects. In the diabetic patients, the relationships between oesophageal emptying, gastric emptying, gastrointestinal symptoms, autonomic nerve function and glycaemic control were examined. The percentage of the solid meal remaining in the stomach at 100 min (p<0.001), the 50% gastric emptying time for the liquid meal (p<0.05) and oesophageal emptying (p<0.05) were slower in the diabetic patients compared to the control subjects. Scores for upper gastrointestinal symptoms and autonomic nerve dysfunction did not correlate significantly (p>0.05) with oesophageal, or gastric emptying. The 50% gastric emptying time for the liquid meal was positively related (r=0.58, p<0.01) to the plasma glucose concentration at the time of the performance of the gastric emptying test and the lag period, before any solid food emptied from the stomach, was longer (p<0.05) in subjects with plasma glucose concentrations during the gastric emptying measurement greater than the median, compared to those with glucose concentrations below the median. These results indicate that delayed gastric and oesophageal emptying occur frequently in Type 2 diabetes mellitus and that delayed gastric emptying relates, at least in part, to plasma glucose concentrations.     

Influence of gender and menopause on gastric emptying and motility

The aims of this study were to determine (a) if there are differences in gastric emptying rates of a mixed liquid and solid meal between men and women, (b) if menopausal status affects gastric emptying, and (c) whether differences in solid emptying rates are associated with alterations in postprandial antral motility parameters. A dual-isotope technique was used to measure gastric emptying in 20 men, 18 premenopausal women, 14 postmenopausal women, and 8 postmenopausal women taking estrogen and progesterone hormone replacement. A multilumen perfusion catheter was used to measure antral motility in 6 men and 6 premenopausal women. Premenopausal women, postmenopausal women, and postmenopausal women taking oral estrogen and progesterone had slower gastric emptying of liquids than did men (p less than 0.025, less than 0.05, and less than 0.025, respectively). Both premenopausal women and postmenopausal women taking sex hormone replacement therapy had slower emptying of solids than did men (p less than 0.025 and less than 0.05) but, in contrast to liquids, postmenopausal women not on hormone replacement emptied solids at a rate similar to that of men. There were no differences in postprandial antral motility parameters between men and premenopausal women. These findings support the hypothesis that sex steroid hormones have variable inhibitory effects on gastric emptying of a mixed meal and this should be considered when studying gastric emptying in disorders that occur predominantly in premenopausal women.     

Gastric emptying of liquids and solids in the portal hypertensive rat

The effects of portal hypertension on gastric motor function were investigated using the rat staged portal vein ligation model. Gastric emptying of liquids and solids was studied separately following meals labeled with 51Cr or 99Tc by whole stomach scintillation counting. Portal hypertension was consistently established in experimental rats (splenic pulp pressure: mean +/- SEM, portal hypertension versus control, 16.8 +/- 0.7 vs 11.8 +/- 0.7 mm Hg, P less than 0.0001). Although liquids were emptied in an exponential manner and solids in a linear fashion, gastric emptying of both meals was more rapid in the experimental rats. Ten minutes after the liquid meal, more than 50% of the meal had emptied from the stomachs of portal hypertensive rats while only one third of the meal had cleared in the control group (P less than 0.02). Gastric emptying of the solid meal was significantly accelerated in experimental rats at 60 and 120 min (percent meal remaining: portal hypertension versus control, 41.9 +/- 4.0 vs 55.4 +/- 3.5 and 21.5 +/- 4.9 vs 32.6 +/- 4.3, P less than 0.05). Stomachs of portal hypertensive animals were heavier (P less than 0.009) and histologic examination revealed submucosal edema. Thus, a possible mechanism of the disrupted gastric motor function in portal hypertension is decreased gastric wall compliance secondary to edema.     

Effect of cisapride on gastric and esophageal emptying in insulin-dependent diabetes mellitus

The effects of cisapride on gastric emptying, esophageal emptying, gastrointestinal symptoms, and glycemic control were evaluated in 20 insulin-dependent diabetics who had delayed gastric emptying of the solid or liquid component of a meal, or both. A double-isotope technique was used to measure gastric emptying, and esophageal emptying was measured as the time for a bolus of the solid meal to enter the stomach. On 2 days each patient received cisapride (20 mg) or placebo orally, 60 min before an esophageal and gastric emptying test. A third gastric and esophageal emptying test was performed after each patient had orally taken 10 mg of cisapride or placebo q.i.d. for 4 wk. Single-dose cisapride increased esophageal emptying (p less than 0.01) and both solid and liquid gastric emptying (p less than 0.001). The response to cisapride was most marked in patients with the greatest delay in esophageal and gastric emptying (p less than 0.05). After administration of cisapride for 4 wk, gastric emptying of solid and liquid were faster (p less than 0.001), but esophageal emptying was not significantly different from the placebo test. Upper gastrointestinal symptoms were less after cisapride (p less than 0.05), whereas there was no change on placebo (p greater than 0.2). Plasma glucose and glycosylated hemoglobin concentrations were not different after cisapride compared with placebo. These results indicate that single-dose cisapride increases esophageal emptying in insulin-dependent diabetics and that chronic administration of cisapride is effective in the treatment of diabetic gastroparesis.     

Influence of acid-pepsin secretion on gastric emptying of solids in humans: studies with cimetidine.

The commonly accepted model for gastric emptying suggests that the 'antral mill' is responsible for the triturition and subsequent emptying of solid food from the stomach. Little is known about the contribution to solid emptying made by other digestive mechanisms such as acid-pepsin secretion. We have investigated the effect of inhibiting gastic secretion on the rate at which a solid test meal emptied from the stomach. Using a radiolabelled beefburger, we performed paired gammacamera studies on consecutive days in 10 fasted, healthy volunteers to compare gastric emptying of the test meal with and without oral cimetidine (400 mg 1 hour before the test, 800 mg at the start of the meal). Inhibition of acid-pepsin secretion by cimetidine was associated with an appreciable delay in the rate of emptying of the burger from the stomach (T50 cimetidine 187 (16) min (mean (SEM); T50 no cimetidine 146 (15) min; p less than 0.01, paired t test). This delay was related to a change in the slope of the emptying profile and was not associated with a prolonged lag phase. These results may be explained by the relative achlorhydria and reduced pepsin activity induced by cimetidine impairing the breakdown of solid food into particles small enough to leave the stomach.     

Comparative effects of duodenal and ileal intubation on gastric emptying and postprandial antral, pyloric, and duodenal motility

The influence of gastric and small-intestinal intubation on fed patterns of antropyloroduodenal motility and gastric emptying of a solid meal has been investigated in normal volunteers. In 10 subjects a manometric assembly was passed as far as the fourth part of the duodenum; in 8 other subjects the terminal ileum was intubated; and a further 8 subjects were not intubated. The manometric assemblies were similar, apart from their length, and both incorporated a sleeve/side hole assembly located across the pylorus. All subjects ingested a meal of 100 g 99mTc-labelled liver/ground beef. There was no significant difference in either the lag phase or the linear emptying phase of gastric emptying between the control and duodenal intubation groups. The emptying phase of the test meal, but not the lag phase, was slower (p less than 0.01) in the ileal intubation group than in the non-intubated and duodenal intubation groups. There were fewer (p less than 0.01) antral pressure waves in the ileal than in the duodenal intubation group. We conclude that ileal but not duodenal intubation has an important inhibitory influence on gastric emptying and antral motility.     

Gastric motility and emptying in normal and post-vagotomy subjects.

The effects of proximal gastric vagotomy (PGV) and vagotomy with pyloroplasty (V and P) on gastric motility were studied using a solid meal labelled with a radiopharmaceutical agent. In having on-line computer facilities it was possible not only to record the rate of emptying but also to analyse the relative roles of the fundus and the antrum within the overall framework of gastric emptying. In normal subjects the fundus filled and then emptied in an almost linear pattern. The antrum, however, did not completely fill until well after the meal was eaten and thereafter appeared to maintain a constant volume during the study. The redistribution of contents between fundus and antrum was reflected in the total stomach emptying curve as a delay, or lag phase before gastric emptying commenced. After both types of vagotomy fundic filling was delayed, representing a slower eating time, which was presumably due to early satiety. Antral filling and volume was disturbed only after V and P, which was also reflected by a loss of the lag phase seen on the total stomach curve. PGV retained antral function but there was significant delay in the redistribution of contents between fundus and antrum, though this did not have clinical significance. The rate of emptying was unaffected by either operation. It was concluded PGV did maintain antral function and a more normal pattern of emptying compared with V and P. After V and P the changes in antral function were considerable and these changes are probably associated with some of the complications resulting from this operation.     

Gastric pacemakers.

Gastric electrical control activity (ECA) controls the sequence of occurrence of contractions in the gastric wall. Normally, the direction of phase lag among control waves is aborad, and hence a ring of contraction originates in the corpus and moves distally. This study was undertaken to determine if a reversal in the direction of phase lag among control waves by an electronic pacemaker surgically implanted near the pylorus in dogs would reverse the sequence of contractions and hence delay gastric emptying. Electrical stimulation was applied at 5.8 to 6.0 pulses per min, 50 to 80-msec pulse width, and 10 to 14-v pulse amplitude. Liquid gastric emptying was measured by introducing 400 to 600 ml of phenol red or phenol red plus barium sulfate by a nasogastric tube through an esophagostomy into the stomach and withdrawing the remainder after 5- and 15-min periods. Solid emptying was measured by means of radiological image intensifier observation of the gastric emptying of small barium-filled balls. The study shows that an electronic pacemaker implanted in the antrum reverses the normal aborad direction of movement of contractions and delays the gastric emptying of both liquid and solid meals.     

Relationship between postprandial motor activity in the human small intestine and the gastrointestinal transit of food

Profiles for gastric emptying and colonic filling were determined in 20 normal volunteers by means of a gamma camera and dedicated minicomputer after ingestion of a radiolabeled solid meal. These were compared with intraluminal pressure activity, recorded simultaneously from three sites (each separated by 50 cm) in the small intestine by infusion manometry. Recordings were continued for at least 8 h or until all the radioactivity appeared in the colon. Colonic filling was approximately linear, occurring at an average rate of 16% of the meal residues per hour. There were significant inverse correlations (p less than 0.01) between the pressure activity in the proximal jejunum during the first 3 h after ingestion and the times taken for 50% and 80% of the meal residues to enter the colon, and direct correlations between total small intestinal pressure activity and the half-time for gastric emptying. Phase III of the interdigestive migrating motor complex appeared between 3 and 9 h after ingestion (when between 15% and 80% of the meal remained in the small intestine), but did not necessarily migrate to the next recording site until much later. The time of appearance of phase III in the proximal jejunum was directly correlated with the half-time for gastric emptying (p less than 0.05) and with the intraluminal pressure activity recorded at that site during the first 3 h after food ingestion (p less than 0.01). The time at which 80% of the meal residues had entered the colon was significantly shorter in 6 subjects, in whom a postprandial activity front appeared to migrate throughout the small bowel, compared with 13 subjects, in whom this did not occur (5.0 +/- 0.5 h vs. 7.0 +/- 0.4 h, p less than 0.01). These studies have shown that gastrointestinal transit of a solid meal is related to both fed and fasted intraluminal pressure activity in the small intestine.     

Effect of pectin on gastric emptying and gastroduodenal motility in normal subjects

The effects of pectin ingestion on gastric emptying, gastroduodenal motility, and plasma levels of glucose, insulin, and glucagon were studied. Initial studies demonstrated that 15 g of pectin was the optimal dose. Subsequently 6 healthy male volunteers were studied on 4 separate days at random. On day 1, gastric emptying of a liquid and a solid meal was assessed by radioisotope technique using 99mTc-dithiopropylthiomine. On day 2, the gastric emptying study was repeated with the addition of pectin to each meal. Plasma levels of glucose, insulin, and glucagon also were determined during these 2 days. On day 3, the effects of liquid and solid meals on gastroduodenal motility were assessed by means of a perfused catheter system. On day 4, the motility study was repeated with the addition of pectin to each meal. Pectin supplementation caused a significant prolongation of gastric emptying half-time of both liquid and solid meals (p less than 0.05). The addition of pectin, however, did not have any significant effect on gastroduodenal motility other than increasing the duodenal motility index 10 min after the liquid meal. The addition of pectin to the liquid meal lowered plasma levels of insulin at 15, 30, and 45 min, and glucagon levels 15 min after the meal. No effect was noted on blood sugar levels. On the other hand, the addition of pectin to the solid meal had no effect on plasma levels of glucose, insulin, and glucagon. We conclude that pectin supplementation delays gastric emptying of both liquid and solid meals in normal human subjects without causing notable changes in gastroduodenal motility or significant variations in pancreatic hormone plasma levels. The pectin effect on gastric emptying may be caused solely by increasing the viscosity of the meals.     

Opposite effects of kappa-opioid agonists on gastric emptying of liquids and solids in dogs

The influence of oral (p.o.) administration of kappa-(U-50488, tifluadom) and mu- (morphine, DAGO) opioid substances on gastric emptying of liquids and solids in a standard canned dog food meal was evaluated using a double-radiolabeled technique in dogs fitted with gastric cannulas. One hour after feeding, 28.6% +/- 3.6% (mean +/- SD) of the solid phase and 27.1% +/- 8.6% of the liquid phase of the meal had been emptied. Both U-50488 and tifluadom given orally (0.01-0.1 mg/kg) significantly increased (p less than 0.05) the 1-h emptying of the solid phase of the meal by 23.1%-49.6%. In contrast, both drugs significantly reduced emptying of liquids. These effects were not reproduced when similar doses were given intravenously. Oral administration of morphine or DAGO (0.01-0.1 mg/kg) did not affect gastric emptying, whereas an inhibited emptying of solids was observed for morphine at a higher dose (1 mg/kg p.o.). At a dose of 100 micrograms/kg i.v. both naloxone and MR 2266 (0.1 mg/kg) abolished the effects of orally administered U-50488 on gastric emptying of solids and liquids. It is concluded that kappa- but not mu-agonists act locally to alter gastric emptying of a standard meal in dogs, having opposite effects on solid and liquid phases. A selective local stimulation of kappa mucosal or submucosal receptors of the gastroduodenal area may explain such effects.     

Effect of ICS 205-930 (a specific 5-HT3 receptor antagonist) on gastric emptying of a solid meal in normal subjects.

The effects on gastric emptying of a solid meal of the specific 5-HT3-receptor antagonist ICS 205-930, 10 mg and 20 mg intravenously were assessed with a scintigraphic technique in 12 normals. The 50% emptying time was less, the lag phase was shorter and the post lag emptying rate was faster after 20 mg ICS 205-930 (p less than 0.02). After 10 mg ICS 205-930 the lag phase was significantly shorter compared with placebo (p less than 0.04). These results suggest that 5-HT3 receptors may be involved in the regulation of gastric emptying in man.     

A simple double radiolabeled technique to evaluate gastric emptying of canned food meal in dogs. Application to pharmacological tests

Simultaneous measurement of solid and liquid phases of gastric emptying for a standard canned food meal was performed using a double radiolabeled technique in six dogs equipped with gastric cannula. The liquid phase (100 ml of tap water containing [14C] polyethylene glycol 4000) was added to the solid phase (400 g of canned food containing 10 g of liver tagged with [57Co] cyanocobalamine) and was presented for spontaneous eating to the dog. Determinations of individual emptying curves for solid and liquid phases were performed by total collection of gastric contents at one hour intervals 1 to 4 h after feeding. Regression constants and correlation coefficients indicated that liquids evacuated as a logarithmic function of time while solids emptied linearly between 1 and 4 h after the meal. Using this method we showed that orally (PO) administered metoclopramide (1 mg/kg) and domperidone (5 mg/kg) increased emptying of liquid phase measured one hour after eating by 106.3 p. 100 and 59.4 p. 100, respectively, but did not modify that of solid phase; in contrast, cisapride (5 mg/kg PO) increased emptying of the solid and liquid phases at one hour by 41.5 p. 100 and 73.0 p. 100, respectively.