Total Gastric Pouches Research Articles

Protection by sucralfate against indomethacin induced gastric ulceration in the guinea pig

In the management of rheumatic diseases, peptic ulceration associated with anti-inflammatory drug therapy is a major problem and seriously limits the usefulness of these agents. In acute experiments with a guinea pig total gastric pouch preparation, gastric damage induced by the prostaglandin synthetase inhibitor indomethacin was shown to be enhanced by preliminary mucosal exposure to bile salts. In the present study, using the same preparation, we report that sucralfate, a basic aluminium salt of sucrose octasulphate, completely prevents the gastric damage observed in pouches exposed to sodium taurocholate and indomethacin. Prevention is shown not to relate solely to bile salt binding or to the weak antacid property of sucralfate.

Rapid induction of gastric ulceration in guinea pigs by sequential exposure to a barrier breaker and indomethacin

In short term experiments under halothane anesthesia, guinea pig total gastric pouches were initially and terminally exposed to 0.1 M HCl for 30 min. During an intervening 50-min test period, the gastric mucosa was exposed at pH 7.3, either to a barrier breaker (lysolecithin or diluted bile or sodium taurocholate) or to phosphate buffered saline (PBS) for half of the period, followed by exposure to indomethacin or further PBS for the second half of the test period. Scoring of mucosal damage was assessed from coded photographs and histological slides and by measurement of the transmucosal potential difference. In comparison with controls exposed only to PBS in the test period, indomethacin did produce minor but significant mucosal damage, whereas over this short time interval, the barrier breaking agents did not. Sequential exposure of pouches to lysolecithin and indomethacin caused a highly significant increase in ulceration, compared to controls or to indomethacin or lysolecithin exposure separately.

Effects of nutrients on acid secretion by innervated total gastric pouch in conscious rats

In conscious rats with innervated total gastric pouches, intravenous infusion or duodenal intubation with fat and glucose decreased gastric acid secretion while amino acids produced the opposite effect. Intravenous infusion of amino acids strongly increased plasma gastrin, but fat and glucose had no effect. Plasma gastrin increased after duodenal intubation with all three nutrients, amino acids being the most effective. Mechanisms of action of gastrin release and acid secretion are discussed concerning the route of nutrients administration which could play a role in the liberation of known or unknown stimulatory or inhibitory factors from intestinal cells.

Secretions of isolated total gastric pouches in fasting and fed rats

In the fasting state, the secretions of isolated total gastric pouches were higher than what was found in classical gastric fistulae. Serum gastrin was lower in operated rats than in normal non-operated rats. The proximal duodenum would contain a substance which inhibited volume and acidity secretion and stimulated pepsin secretion. This role could be developed upon secretin and its family present in high concentration in the upper duodenum. If the vagus was necessary to volume and acid secretion, its action on pepsin secretion was strengthened by the proximal duodenum. After an intestinal meal, all secretions were enhanced, confirming the hypothesis that the intestine would contain an hormone which would act through the vagus, principally for volume and acid secretions and partially for pepsin secretion.

Effect of mast cell degranulation on gastric mucosal damage produced by sodium taurocholate in the rat

The source of the histamine released during damage to the gastric mucosa has been investigated in rats using perfused total gastric pouches. Two groups of rats were treated with either intraperitoneal normal saline or compound 48/80, an agent that produces mast cell degranulation, over a 5-day period. On the 5th day, total gastric pouches were prepared and connected to a perfusion circuit that enabled a 20-ml volume to be circulated through the pouches. The experiments consisted of three 30-min periods during which transmucosal potential difference was monitored and ionic (hydrogen and sodium) flux measured; standard acid solution was used in the first two periods and a taurocholate solution in the third. Sodium taurocholate produced a significant increase in ionic flux and fall in the potential difference, the magnitude of the changes being similar in the 48/80- and saline-treated groups. Histamine was released from the mucosa in significantly greater amounts during the taurocholate period, and the increase was similar in both groups of rats. Histological examination of the stomachs confirmed mast cell degranulation in the 48/80-treated groups. We conclude that the histamine released during mucosal damage is probably derived from the “nonmast cell pool” and that this histamine may play a role in mediating the mucosal damage.

Effect of lysolecithin on gastric mucosal structure and potential difference.

The effect of lysolecithin (100 mg%) on the guinea-pig gastric mucosa was studied by instilling a solution for 30 minutes, preceded and followed by 100 MN HCl into 10 total gastric pouches. Ten control animals had HCl throughout. Lysolecithin produced a significant change in transmucosal potential difference, macroscopic erosions, and mucosal damage on histology and electron scanning microscopy. None of these changes was seen in the control animals. This is further evidence that the reflux of lysolecithin from the duodenum is an important factor in causing active gastritis and gastric erosions.

The effect of duodenal regurgitation into the canine stomach on gastric secretion

Submitted for publication December 8, 1972. THE POSSIBLE EFFECT OF DUODENAL REGURGITATION on gastric secretion has long attracted considerable interest. At the turn of the century Sokolov [19] observed increased secretion from Pavlov pouches after instillation of bile into the dog stomach. 1924 Meyer et a,Z. [13] recorded a moderate increase in the Pavlov pouch secretion after similar circumstances, especially if the pouch was already secreting. In 1936 Kim and Ivy [lo] used a total gastric pouch as measuring organ, t,hey found bile to be a mild stimulus for acid secretion, whereas pancreatic juice did not stimulate at all. Kaulbersz et al. [9] reported in 1942 that bile introduced into the stomach of dogs with Pavlov pouches increased the secretory response to histamine. In dogs with Heidenhain pouches bile failed to stimulate secretion. In 1944 Beamer et al. [l] . t d d th 1 in ro uce ra er arge volumes of bile into dogs with gastric and duodenal fistulas. They noted a secretion of gastric juice after a latent period of 30-45 min. Bile introduced into the duodenum stimulated gastric secretion only when it was allowed to regurgitate into the stomach. Again, the increase was not very large. In later years clinical observations on patients with gastric ulcer disease have placed much emphasis on regurgitation of

Effect of local gastric trauma on gastric response to histamine stimulation.

The effect of injury on the gastric mucosal response to histamine stimulation has been investigated in dogs by 2 technics. (1) Exposing the intact surface of the stomach to several kinds of trauma, e.g., friction, heat, salt, alcohol, and formalin. It was found that the surface of the traumatized area, in each instance, was coated with an alkaline surface of pH 7–9. This alkalinization of the surface after trauma was not affected by submucosal infiltration of local anesthetic. (2) Total gastric pouches in stimulated and unstimulated dogs were filled with ethanol (50% and 70%). In stimulated animals, the gastric secretory output of volume and acid were considerably reduced. In nonstimulated animals, there was a transient rise in the volume of gastric juice after ethanol instillation followed by a reduced output. However, the concentration of acid was low after ethanol administration.

Histamine Secretory Tests in Cats: An Evaluation of Results Based Upon Hollander's Two-Component Theory

Summary A method is described of performing acute total gastric pouch secretory studies in anesthetized cats. The maximal secretory capacity of the gastric epithelium in these preparations was influenced by the duration of histamine administration as well as the dose. It is possible to obtain a larger output of gastric juice for a short period by doubling the dose of histamine each 2 hours than by giving a larger dose over a prolonged test. The correlations between the ionic concentrations in the stimulated and in the unstimulated cats are on the whole consistent with Hollander's two-component theory of gastric secretion. The composition of the two components differs in the two states, the chief difference being an increase in the K concentration in the nonparietal cell secretion on stimulation, with a corresponding decrease in the K in the parietal cell secretion. Histamine increases the rates of both secretions with a greater increase in the parietal cell secretion. The reason for the K content of parietal secretion, which is at variance with the Hollander theory, is not clear but may be due to species difference, to retained innervation of the stomach or to the anesthetic.

The Effect of Gastric Distension on Duodenal Aspirates in Man

The general impression for many years has been that the secretin and pancreozymin mechanisms are largely responsible for the control of pancreatic secretion. Recently, Lundh 1 has shown that there were always proteolytic enzymes in the small intestine of the Billroth I patient and about one­ third of Billroth II patients had no such enzymes in their small intestines. Differences in the degree of gastric distension were sug­ gested as an explanation for these observa­ tions. This idea was tested in a series of animals. It was found that distension of the stomach of the dog with a condom to a pressure of 12 to 15 mm. Hg, did indeed increase pancreatic flow and protein pro­ duction in every case. 2 Vagotomy eliminated the response, usually only temporarily, but if splanchnicectomy was done as well, the distension response did not reappear over a 2- to 6-month period. 3 Splanchnicectomy alone did not influence the reflex. 4 Distension of vagally innervated total gastric pouches resulted in an increase in pancreatic flow, whereas there was no response to distension of a vagotomized pouch. In antrectomized dogs with gastrojejunostomy or gastroileos­ tomy, distension of the remaining stomach stimulated pancreatic secretion as before. In dog pancreases maximally stimulated with secretin, the protein content of the juice increased in response to gastric dis­ tension. On the basis of these experiments we have concluded that there is a reflex pancreatic secretory response to gastric distension which is mediated primarily by the vagus and secondarily by the splanch­ mc nerves.

EFFECTS OF AUTONOMIC BLOCKING AGENTS ON GASTRIC SECRETION AND ULCERATION INDUCED BY CINCHOPHEN

Effects of anticholinergic drugs on gastric secretin induced by cinchophen were investigated on dogs with total gastric pouch, and it was found out that Antrenyl, Pro-banthine and Tropin all strongly inhibited such secretion, but that a little larger doses than that of insulin were necessary ; effect of Banthine was rather inferior to the above. These anticholinergic drugs were not considered to exert any inhibitory action on the hypothalamic-pituitary-adrenocortical system, which is related to the gastric secretion by cinchophen, but to inhibit the release of the secretory substance into the stomach by acting on its glandular cells. Regitin and chlorpromazine did not show any inhibitory acticn on gastric secretion by cinchophen.Combined administrarion of cinchophen and Tropin for 3 weeks produced ulcer as in controls.

Studies on the physiology of the gastric antrum; effect of antrum resection on secretion of gastric juice from the isolated stomach.

Recent studies from this laboratory, as well as elsewhere, have demonstrated that the antrum of the stomach is an important endocrine organ, distinct in function from other parts of the gastrointestinal tract. An understanding of the endocrine function of the antrum and of its external secretion should be helpful in the surgical treatment of peptic ulcer and provide a more complete understanding of the physiology of gastric secretion. In the total gastric pouch, the antrum is isolated from contact with food or distending stimuli and is continually bathed in the undiluted acid gastric secretion of the fundus. In a previous study from this laboratory it was concluded that in this situation the antrum is quiescent.1Removal of the antrum from the isolated stomach and its transplantation to the duodenum or to the transverse colon as a diverticulum caused a tremendous augmentation in gastric secretion. This stimulation in gastric secretion

Role of antral exclusion in development of peptic stomal ulcer.

Conclusions1. Exclusion of the antrum from continuity with the residual gastric pouch is the chief ulcerogenic factor in the Sauvage operation in which the antrum is anastomosed to the esophagus (Group II dogs). 2. Stomal peptic ulcer was not observed in vagally innervated total gastric pouches when the antrum remained in contact with the residual gastric pouch (Group I dogs). 3. Augmentation of the secretion of acid from an isolated Heidenhain pouch attends antral migration or exclusion (Group II dogs). Diminution of secretion from such a pouch was observed when the vagally innervated entire stomach, with the antrum in its normal position, was attached to the side of the duodenum as a blind pouch (Group I dogs).

An investigation of the question of histamine tolerance

1. 1. The subcutaneous administration of histamine to dogs with total gastric pouches does not result in tachyphylaxis, as measured by the gastric secretory response. 2. 2. A gradual reduction in gastric secretory response is noted in the total pouch dogs when histamine is administered (1) at three-hour intervals, (2) twice a day for a four-day period, and (3) eight to twelve times a month for a six-month period. 3. 3. Under similar conditions, Heidenhain pouch dogs do not show this decreasing response, nor do they show a decreasing response when histamine is given twice daily, on alternate days, for three weeks. 4. 4. It may be concluded that the decreasing response noted in total pouch dogs is related to the greater loss of gastric juice and to the poorer reserve nutrition of the total pouch dogs. 5. 5. The opinion is expressed that animal experiments have so far failed to provide an experimental analogy for the therapeutic effect claimed for histamine “desensitization” in allergy.