Pavlov Pouch Research Articles

Plasma Gastrin and Gastric Acid Responses to Sham Feeding and Feeding in Dogs

Gastric acid secretion and plasma gastrin concentrations were determined during fasting and following sham feeding or feeding in dogs with Pavlov pouches or gastric fistulae. Sham feeding caused immediate elevations of plasma gastrin concentrations that rapidly returned to basal levels following the onset of acid secretion although acid was continuously secreted for several hours. Sham feeding with the gastric fistula open produced higher gastrin concentrations and acid output than with the fistula closed. Feeding raised the plasma gastrin concentrations considerably higher than sham feeding in the same dogs although the peak acid output equaled that following sham feeding with gastric fistula open. The delay in onset of acid secretion was more pronounced during feeding than during sham feeding. Atropinization did not significantly influence basal plasma gastrin concentration but virtually abolished the gastrin response to sham feeding. Plasma gastrin responses were observed following feeding despite atropinization.

Potentiation of the gastric secretory response to sham feeding in dogs by infusions of gastrin and pentagastrin.

AbstractThe gastric acid secretory response to sham feeding in dogs provided with esophagostomies and Pavlov pouches was related to the length of the sham feeding period. In antrectomized dogs the response even to prolonged sham feeding (30 min) was small. When a small supra‐threshold dose (0.30 μg/kg/h) of synthetic human gastrin I or pentagastrin was infused, these dogs responded markedly to a short period of sham feeding (1 min), When the sham feeding period was prolonged to 10 min subthreshold amounts of gastrin and pentagastrin (0.06 μg/kg/h or less) sufficed to enhance the sham feeding response. The enhancement fulfilled the criterion proposed by Gaddum for true potentiation. The pepsin output was also increased when the sham feeding period was prolonged. In the antrectomized dogs pepsin output after sham feeding was not significantly changed when the dose of gastrin infused was increased from 0.06 to 0.30 μg/kg/h or when the dose of pentagastrin was increased from 0.30 to 1.20 μg/kg/h.

Influence of secretin and cholecystokinin on canine gastric secretion elicited by food and by exogenous gastrin.

AbstractThe present study showed that in Pavlov pouch dogs gastrin stimulated acid secretion was more markedly inhibited by secretin and cholecystokinin than the secretion elicited by food. The acid secretory response to a test‐meal was only moderately reduced by 3.0 U of secretin/kg/h; the reduction was not statistically significant. In 2 of 3 tested dogs inhibition of the secretion after a test‐meal was more marked when 3.0 U of cholecystokinin (a 10 % pure preparation)/kg/h was administered. However, this dose of cholecystokinin caused some side effects, such as decreased appetite, in the dogs. These doses of cholecystokinin and secretin probably produce unphysiologically high blood levels of the hormones. In spite of the high doses the acid secretory response to a test‐meal was never abolished. This makes it doubtful if these hormones should be regarded as physiologically important inhibitors of gastric acid secretion. Pepsin output after a meal was clearly enhanced by a concomitant infusion of 3.0 U of secretin/kg/h. On the other hand, the same number of units of cholecystokinin markedly inhibited the pepsin output after a meal.

Relation between stimulatory effect on gastric acid secretion and antral absorption of chemical compounds.

Five Heidenhain and two Pavlov pouch dogs were used to study the influence of acidity variations within the isolated antrum on absorption and on gastrin release by one ionizable (choline) and two unionizable compounds (ethanol, n-propanol). Absorption of ethanol and n-propanol was determined by measuring the concentration of the alcohols in the portal blood, in peripheral venous blood, and in the antrum. The constants of absorption were identical for the two alcohols at pH 7. Even though gastrin release by both alcohols was inhibited at low pH levels (pH < 2), the constants remained the same at pH 3 and pH 1 for ethanol and were only slightly lowered for n-propanol (instillation of 10% v/v solutions). Antral perfusion at various pH levels with graded concentrations (2, 4, and 8% solutions) of choline showed a significant increase of free plasma choline at pH 7 and a slight increase at pH 5 with 8% solutions, but no increase with 1–4% choline solutions of pH 7, 5, 3, or 1. Acid output during choline applic...

Effect of satiety center damage on food intake, blood glucose and gastric secretion in dogs.

Goldthioglucose is capable of damaging the ventromedial hypothalamus (satiety center) and inducing obesity in dogs, similar to the effects reported in mice and rats. Body weight was increased at a rate of 10% or more in 51% of the goldthioglucose-treated dogs during an 8-week period. Daily food intake was also increased, significantly, as high as 20% or more, in 68% of the goldthioglucose-treated dogs. Fasting blood-glucose levels did not show any change in obese animals, but blood glucose utilization increased significantly as compared with control animals. The sensitivity of glucose regulating mechanisms to insulin was enhanced by goldthioglucose treatment. Fasting gastric secretion in Pavlov pouch dogs, increased in volume and acidity, above preinjection levels of goldthioglucose, but this effect was not seen in Heidenhain pouch dogs.

Gastrin and acid studies in the pouch dog. II. Effect of truncal vagotomy on response to food and insulin hypoglycaemia.

Serum gastrin and acid secretion were studied in one Heidenhain and two Pavlov pouch dogs before and after truncal vagotomy. The Heidenhain pouch dog showed an increase in basal serum gastrin and basal acid output following vagotomy, and the secretion of both gastrin and acid was also increased by a meat meal, with prolongation of the duration of response. The Pavlov pouch dogs, although showing a similar rise in both basal and meat-stimulated gastrin after vagotomy, showed a fall in both basal acid output and the peak acid output after meat compared to the levels attained before vagotomy. Insulin hypoglycaemia failed to stimulate either gastrin or acid release post-vagotomy.

Effect of nicotinic acid on gastric secretion of acid in human subjects and in dogs.

The effect of nicotinic acid on gastric secretion was studied in 19 fasting patients who had coronary heart disease and hyperlipoproteinemia. Among 10 patients with basal secretion of acid, 9 had increased acid output following oral administration of 0.5 g of nicotinic acid — the increase ranged from 13 to 232 per cent. Also in Pavlov pouch dogs, i.v. infusion of nicotinic acid gave rise to a significant increase in gastric acid output. The mechanism behind gastric stimulatory action of nicotinic acid is unknown.

The gastric secretory response to insulin: an 'all-or-none' phenomenon?

Dogs were prepared with Pavlov pouches which could be perfused with saline so as to detect rapidly changes occurring in acid secretion.Dose-response studies were performed by the intravenous injection of insulin (0.06, 0.12, 0.25, 0.5, or 1.0 unit/kg). Both the magnitude of peak response and the duration of response were dose-related and both were related to the magnitude of fall in plasma glucose. These results are not consistent with an ;all-or-none' hypothesis for insulin-stimulated gastric acid secretion, but favour the alternative hypothesis that insulin provides a graded glycopenic stimulus producing a graded secretory response.

Inhibition of gastric secretion by atropine in conscious rats.

1. The effect of atropine on acid and pepsin secretion, stimulated by feeding, vagus excitation or infusions of gastrin, histamine and methacholine, was studied in conscious rats provided with a Pavlov or a Heidenhain pouch.2. The acid and pepsin secretion in response to food was substantially suppressed by atropine in the Pavlov pouch.3. The strong stimulatory effect of 2-deoxy-D-glucose on acid and pepsin secretion in the Pavlov pouch was almost abolished by atropine.4. A plateau secretion of acid obtained by infusion of submaximal doses of hog gastrin II, was significantly inhibited by atropine in the Pavlov and the Heidenhain pouch.5. Methacholine-induced acid and pepsin secretion in the denervated Heidenhain pouch was nearly completely inhibited by atropine.6. A plateau secretion of acid evoked by infusing histamine in a near maximal dosage was inhibited by atropine to the same extent as the gastrin-induced secretion in the Pavlov pouch.7. The mode of action of atropine as a gastric secretory inhibitor is discussed.

Effect of Antrectomy on Acid Secretion from Pavlov Pouches in Cat

In cats with Pavlov pouches antrectomy increased maximal acid secretion in response to histamine (40% increase) and to pentagastrin (30% increase). The mechanism of this effect is not known.

Failure of high PCO2 in the duodenal bulb to inhibit gastric acid secretion.

AbstractGastric acid secretion was stimulated by intravenous infusion of pentagastrin (ICI 50 123) in dogs with Pavlov pouches and isolated pouches of the duodenal bulb. Elevation of the Pco2 to 150 or 700 mm Hg in the bulbar pouches did not reduce the gastric acid output. It is suggested that the high CO2 tension which normally exists in the canine duodenum during periods of stimulated gastric acid secretion is not involved in the activation of the bulbar mechanism inhibiting the gastric acid secretion.

Effect of Secretin on Gastric Acid Secretion in Response to Cholinergic Stimuli

Four dogs were prepared with antrectomies, gastric fistulas, and Pavlov pouches. Insulin or 2-deoxyglucose given by rapid intravenous injection evoked little secretion from the Pavlov pouches. Therefore, a threshold dose of histamine was given by continuous intravenous infusion and insulin, 0.5 or 0.25 U per kg, or 2-deoxyglucose, 0.15 g per kg, was injected after acid secretion had reached a plateau. This resulted in secretory responses similar to those stimulated by insulin or 2-deoxyglucose in animals with intact antrums. In some experiments secretin, 2 U per kg-hr was added to the intravenous infusion at the time of insulin or 2-deoxyglucose injection. Secretin did not alter acid output in response to insulin or 2-deoxyglucose. Pepsin secretion after 2-deoxyglucose was enhanced by secretin but secretin did not change an already high pepsin response to insulin. Acid and pepsin secretion stimulated by a continuous intravenous infusion of bethanechol was compared with secretory rates when secretin was added to the infusion. Secretin depressed acid and increased pepsin output due to bethanechol. These results were contrasted with those from experiments performed in dogs with gastric fistulas, Pavlov pouches, and intact antrums. In these animals, secretin markedly inhibited acid secretion in response to insulin or 2-deoxyglucose. These data suggest that direct cholinergic stimulation of parietal cells is not vulnerable to inhibition by secretin. The inhibition observed in animals with intact antrums is probably due to an antagonism by secretin of vagally released gastrin. Since bethanechol-stimulated acid secretion was inhibited by secretin in antrectomized animals the response to bethanechol may be due to the release of an endogenous humoral gastric stimulant other than antral gastrin as well as a direct effect of bethanechol on parietal cells.

The secretory pattern of three stomach preparations in the rat.

1. In conscious rats provided with a gastric fistula, or a Pavlov pouch, or a Heidenhain pouch, the secretion of acid and pepsin was studied in the interdigestive state and in response to hog gastrin II. In Pavlov pouches and in Heidenhain pouches the responses to 2-deoxy-D-glucose and to food were established, as were also the responses to gastrin pentapeptide and methacholine in Heidenhain pouches.2. Interdigestive secretion of acid and pepsin is substantial in the gastric fistula and the Pavlov pouch preparation, whereas in the Heidenhain pouch acid secretion is low or scanty, and the ratio pepsin/acid output is higher than in the innervated preparations.3. Feeding evoked secretion of acid and pepsin in the Heidenhain and Pavlov pouches; the increase in pepsin secretion lasted much longer in the Heidenhain than in the Pavlov pouch.4. Methacholine, infused in a threshold dose, augmented the acid output in response to food in the Heidenhain pouch, but did not affect the pepsin output.5. Gastrin II (hog) evoked graded acid responses in the three stomach preparations, and the innervated preparations were more sensitive to gastrin II than the denervated one, whereas stimulation of pepsin secretion was apparent only in the Heidenhain pouch.6. Methacholine, on infusion, in the Heidenhain pouch, gave a maximal acid secretory response, greater than twice that obtained by gastrin, and produced strong stimulation of pepsin.7. Methacholine, infused in a threshold dose, accentuated the acid secretory response to graded doses of gastrin.8. 2-deoxy-D-glucose stimulated acid and pepsin secretion consistently in the Pavlov pouch, whereas in the Heidenhain pouch the response was scanty or absent.9. A large dose of gastrin pentapeptide injected intravenously while a background secretion was maintained by gastrin II, produced in the Heidenhain pouch triphasic changes in the sequence: stimulation, inhibition, stimulation.

Gastric Mucosal Blood Flow Following Damage by Ethanol, Acetic Acid, or Aspirin

The gastric mucosal blood flow in vagally denervated oxyntic gland area (Heidenhain) pouches was estimated by aminopyrine clearance in four 30-min periods after irrigations with acid solutions of ethanol, acetic acid, and aspirin. Mucosal blood flow increased initially when either ethanol or acetic acid was used and subsequently declined with appearance of evidence of gastric mucosal barrier damage. In spite of similar evidence for gastric mucosal barrier damage the mucosal blood flow with the aspirin solutions was, by the fourth period, significantly greater than the mucosal blood flow with the acetic acid solutions. Studies with acetic acid and aspirin solutions were repeated in vagally innervated oxyntic gland area (Pavlov) pouches. The pattern of mucosal blood flow was similar and in those experiments with homogeneous base lines the mucosal blood flow of the aspirin studies in the fourth period was again significantly greater than that of the acetic acid study. Although a greater mucosal blood flow might be considered a beneficial and protective influence, invariable bleeding characterized the fourth period of the aspirin experiments while only inconstant and minimal bleeding was noted in the fourth period of the acetic acid experiments.

Maximal acid response of Pavlov pouches to food and histamine.

Secretion of gastric acid in response to histamine, insulin, and a meal of liver, with and without 5% bone dust, was studied in three dogs with Pavlov pouches and gastric fistulas. The ratios of insulin-induced to histamine-induced secretion were the same in pouch and main stomach indicating that their innervation was equivalent. Meals of a liver and bone dust mixture in amounts of 11 to 44 g/kg resulted in Pavlov pouch acid outputs that were 34 to 56% higher than the maximal response to histamine (p < 0.05 to < 0.001). Liver without bone dust also produced higher acid outputs than histamine. These results indicate that combinations of endogenously generated stimuli can produce a potentiated gastric response which exceeds that produced by histamine alone.

Effect of acid in the duodenal bulb on gastric secretory responses to sham feeding.

AbstractGastric secretion was stimulated by sham feeding in Pavlov pouch dogs with esophageal fistulae and isolated pouches of the duodenal bulb. Reduction of the intrabulbar pH to pH 3–4 inhibited the acid response to sham feeding. Bulbar acidification was more effective in inhibiting acid responses to 1 and 10 min of sham feeding than responses to 30 min of sham feeding. Short periods of bulbar acidification were sufficient to activate the bulbar inhibitory mechanism.

Gastric and Pancreatic Secretion in Response to Gastric Distention in Dogs

In dogs with chronic gastric and pancreatic fistulas, distention of the stomach with a water-filled balloon stimulated water, acid, and pepsin secretion by the stomach and water, bicarbonate, and protein secretion by the pancreas. The gastric response increased with increasing distending volumes up to a maximum with 900 ml. The maximal acid response was about 40% of the maximal response to histamine or gastrin, and the maximal pepsin response was about 60% of the maximal response to insulin and about 10 times the maximal pepsin output to exogenous gastrin. The high pepsin response supports the view that the gastric response to distention is mediated mainly by a vagal reflex. Administration of exogenous gastrin during gastric distention depressed pepsin secretion. Similar inhibition of pepsin secretion by exogenous gastrin had previously been reported to occur in Pavlov pouches stimulated by sham feeding. The high pepsin secretion seen with gastric distention, insulin hypoglycemia, and sham feeding indicate that in all of these circumstances vagal release of gastrin is limited to the small amount required to augment acid secretion in response to direct vagal impulses to the oxyntic glands and is less than the moderate amounts of gastrin that inhibit pepsin secretion. The pancreatic response to gastric distention was small and could best be demonstrated during infusion of a small background dose of secretin. The increase in volume (1 ml per 15 min) was about 6% of the maximal response to endogenous secretin. The increase in protein output (44 mg per 15 min) was about 20% of the response to a large dose of exogenous pancreozymin. The relative contributions of gastrin and of direct vagal impulses to these small pancreatic responses to gastric distention cannot be assessed from the present studies.

Physiology of the Gastrointestinal Tract

Of easily readable size and presenting its material in an attractive format, this work is oriented toward the medical student. It covers the subject under major headings of splanchnic circulation, motor mechanisms, secretion, digestion, and absorption. The bibliography is brief, and controversial points generally are passed over. Although opinions differ over what the medical student should be taught and how material should be presented, coverage certainly offers an adequate background in most areas of gastrointestinal physiology. Hepatic physiology, however, is incompletely examined, and the authors seem not to have decided how to approach this complicated subject. Perhaps hepatic physiology, now so extensive, can be covered adequately only in a separate volume. Some of the material is presented and discussed in a confusing or inadequate manner, especially for a book designed as an introductory text for students. For example, the authors mention results obtained by using a Pavlov pouch, but they

Effect of acid in the duodenal bulb on gastric secretory responses to insulin hypoglycemia.

AbstractGastric acid secretion was stimulated by insulin hypoglycemia in Pavlov pouch dogs with isolated pouches of the duodenal bulb. Perfusion of the duodenal bulb with 0.1 N HCI abolished the secretory response to a low dose of insulin (0.2 I.U. per kg b.w.), whereas the responses to higher doses (0.4 and 0.8 I.U. per kg b.w.) were only partially inhibited. It is suggested that the bulbar mechanism inhibits secretory responses to insulin hypoglycemia by interference with the stimulatory action of gastrin.

Inhibition of Pepsin Secretion by Acid in the Intestine

Following meal, pepsin output from a Heidenhain pouch (HP) is depressed below basal levels, while pepsin output from a Pavlov pouch (PP) increases markedly.^1-3A possible explanation of this difference may be that vagal denervation renders the peptic cells (chief cells) more vulnerable to intestinal inhibitory mechanisms activated by feeding. Fat in the intestine^4,5is known to inhibit pepsin secretion stimulated by a meat meal, histamine, or pilocarpine, but the effect is greater in PP than in HP.⁵Acid in the intestine inhibits pepsin secretion from PP, but in the one HP studied, there was no certain effect. To examine the problem further, we diverted endogenous acid from the upper small bowel segments. The effect of the diversion of acid on pepsin secretion was evaluated in HP stimulated by varying doses of histamine. <h3>Materials and Methods</h3> In three healthy, male, mongrel dogs weighing 19 to 21.5 kg,