Duodenal Inhibition Research Articles

COMPARATION OF EFFICACY OF DIFFERENT PERIOPERATIVE MEDICAL PREPARATION SCHEMES FOR TRANSPAPILLAR ENDOSCOPIC INTERVENTIONS

The intensity of peristaltic activity has significant impact on the duration of transpapillar endoscopic interventions and in some cases (juxtapapillary diverticulum, stenotising papillitis or severe oedema of papilla) can impede operations. Therefore, proper inhibition of duodenal peristalsis is one of the important preconditions for successful fulfilment of such procedures. The aim of the study was to carry out comparative analysis of impact of antispasmodic medications used through the perioperative period on the quality of transpapillar endoscopic interventions. Case histories of patients, who were treated at the Surgical Department of Municipal Enterprise “Sklifosovskiy Poltava Regional Clinical Hospital” for 2017-2019, were investigated, and 75 cases were chosen for further analysis. We divided our cohort in two groups depending on medications used for duodenal peristalsis inhibition: I group – hyoscine butyl bromide (1 ml 2% solution intramuscular injection); II – hyoscine butyl bromide (1 ml 2% solution intramuscular injection), and atropine (1ml 0,1% solution intramuscular injection). Time needed for selective cannulation, total procedure length, number and type of adverse events during manipulation and in early postoperative period were compared between the groups. After statistical data processing the following conclusions were made: 1) proper medical preparation significantly facilitates the implementation of transpapillar endoscopic interventions; 2) combined scheme to reduce duodenal peristalsis, which includes hyoscine butyl bromide and atropine, is not superior to hyoscine butyl bromide alone.

Glucagonlike peptide-1 (GLP-1) participation in ileal brake induced by intraluminal peptones in rat.

The aim of this study was to determine the mechanisms implicated in the gastrointestinal inhibition induced by ovoalbumin hydrolysate infused intraluminally. We studied the site of action, the possible implication of GLP-1, and the nervous mechanisms involved. We prepared anesthetized Sprague-Dawley rats with strain gauges in the antrum, duodenum, and proximal jejunum and a catheter in the duodenum or ileum for peptone infusion. Both intraduodenal (N = 6) and intraileal (N = 5) infusion of ovoalbumin hydrolysate induced inhibition of spontaneous motor activity in the antrum, duodenum, and proximal jejunum. Duodenal inhibition induced by intraduodenal (N = 6) or intraileal (N = 6) infusion of ovoalbumin hydrolysate was reversed by intraarterial infusion of GLP-1 receptor antagonist, exendin (9-39) (3 x 10(-8) mol/kg/40 min). Finally, a combination of the adrenergic blockers phentolamine and propranolol (1 mg/kg, each; N = 7) completely blocked inhibitory gastrointestinal motor actions caused by intraduodenal infusion of ovoalbumin hydrolysate. This study demonstrates that peptone, intraluminally infused, participates in the regulation of gastrointestinal motility through stimulation of adrenergic pathways in anaesthetized rats. Moreover, these effects are partly mediated by GLP-1 secretion. The ileum seems to be the site of action, indicating a role of GLP-1 on the ileal break mechanism.

Duodenal acid-induced inhibition of gastric motility and emptying in rats

The mechanism by which acid in the duodenum inhibits proximal gastric motor function and delays emptying was investigated in urethan-anesthetized and awake rats. Gastric motility inhibited by duodenal acid (0.2 N HCl) in urethan-anesthetized rats was attenuated by 68 and 54%, respectively, by functional ablation of the vagal or spinal sensory innervation with capsaicin. 5-Hydroxytryptamine3 receptor blockade with zacopride (0.2 mg/kg ip) or cholecystokinin (CCK)-A-type receptor blockade with MK-329 (1 mg/kg ip) had no effect on the motility response to acid. In awake rats with chronically implanted gastric and duodenal cannulas, perfusion of the duodenum with acid (0.1 and 0.2 N HCl) inhibited gastric emptying of a nonnutrient liquid (38 and 59%, respectively). Blockade of CCK-A-type receptors reduced by 30% inhibition of gastric emptying induced by 0.1 N HCl. However, functional ablation of the vagal or spinal sensory innervation, 5-hydroxytryptamine3 receptor blockade, or immunoneutralization of secretin by systemic administration of a polyclonal antibody (no. 7842, 1 ml ip) had no effect on acid-induced (0.1 N HCl) inhibition of gastric emptying. Perfusion of the duodenum with 0.2 N HCl but not 0.1 N HCl inhibited proximal gastric motility in awake rats. These results suggest that 1) a duodenal acid load inhibits gastric emptying in part by a mechanism involving CCK and 2) decreased proximal gastric motility plays a minor role in inhibition of gastric emptying in response to acid.

Effects of cholecystokinin and gastrin on gastroduodenal motility and coordination in chickens

Cholecystokinin (CCK) has not been isolated from chicken gut yet and there has been no study on the effects of chicken gastrin (CG), the only gastrin/CCK peptide isolated from avian gut, on gastrointestinal motility. The main objective was to study the effects of CCK and CG on gastroduodenal motility and coordination in chickens. Electrodes for electromyography were implanted in the stomach and proximal and distal duodenum of 4 wk old chickens. Sulphated CCK-octapeptide (CCK8) (10 −10 to 10 −8 moles/kg), CCK-tetrapeptide (CCK4) (2×10 −10 to 2×10 −8 moles/kg) and CG (3×10 −10 to 10 −8 mole/kg) were given in a 10 min i.v infusion. All these peptides induced a dose-dependent inhibition of gastric motility. CCK8 induced a duodenal hyperactivity whereas CCK4 and CG induced a duodenal inhibition. Neither the CCK-A receptor antagonist L364,718 nor the CCK-B receptor antagonist L365,260 (10 −9 − 10 −7 moles/kg) antogonized CCK8 actions. From these results we suggest that the receptors mediating CCK effects are different from those of mammals. The site of action for these peptides is the same in the stomach whereas in the duodenum there are two different ones, one mediating excitation and the other inhibition. These results suggest a physiological role for CCK regulating gastroduodenal motility in birds.

The effect of intracisternal injection of thyrotropin-releasing hormone on gastric and duodenal motility in the urethane-anaesthetized rat

Intracisternal injection of thyrotropin-releasing hormone (TRH; 1-3 micrograms) caused an increase in gastric motility and usually an inhibition of duodenal motility. These effects were abolished by vagotomy and atropine. No inhibition was seen even after tone and motility had been restored to a point at which vagal stimulation could evoke profound inhibition of gastric and duodenal motility. It is concluded that TRH is a specific activator of enteric excitatory pathways and that duodenal inhibition seen in control animals is a consequence of gastro-duodenal inhibitory reflexes.

Alpha 2-adrenergic model of gastroparesis: validation with renzapride, a stimulator of motility

Motility-stimulating drugs can increase gastric antral and intestinal contractions but do not usually enhance emptying unless gastroparesis is present. An alpha 2-adrenergic agonist (SC-39585A) was used to inhibit antroduodenal motility and simulate gastroparesis in dogs. SC-39585A caused dose-related inhibition of emptying of solid and liquid meals as well as the antral and duodenal motility responses to the solid meal. The motility-enhancing agent renzapride (100 micrograms/kg iv) did not enhance emptying of the solid meal under nondelayed conditions. However, at the same dose it partially reversed the delay in solid emptying but only when antroduodenal motility was incompletely (30 micrograms/kg sc) and not totally (100 micrograms/kg sc) inhibited by SC-39585A. This was done in part by antagonizing antral but not duodenal inhibition of motility. Renzapride was also effective orally in reversing the delay in solid emptying. Similarly, renzapride reversed the delay in liquid emptying caused by SC-39585A (30 micrograms/kg sc). An alpha 2-adrenergic agonist can be used to model gastroparesis in dogs by inhibiting antroduodenal motility and can also be used to examine the actions of motor stimulants, such as renzapride, which promote gastric emptying.

Neural control of duodenal motor inhibition by antral contractions in dogs

The mechanism of the inhibition of proximal duodenal motor activity by carbachol-induced antral contractions or by field stimulation was studied in anesthetized dogs that had strain gauges sutured 5 and 10 cm from the pylorus on the antrum and duodenum. The duodenum was excited by vagal stimulation or distal duodenal field stimulation. Duodenal inhibition was studied 1) during a control period and after the pylorus was transected followed by administration of phentolamine, 2) during control and after phentolamine followed by pyloric transection, 3) during control and after prazosin followed by yohimbine, and 4) during control and after yohimbine. Duodenal inhibition was greater when the antral stimulation or duodenal contractions were near the pylorus. Pyloric transection did not significantly reduce this inhibition; phentolamine then abolished it. Prazosin did not abolish inhibition but yohimbine did. In conclusion, antroduodenal inhibition under our experimental conditions was mediated primarily by sympathetic nerves modulating the activity of duodenal cholinergic nerves, which possess alpha 2-adrenoceptors, and to a less extent by intrinsic nerves crossing the pylorus.

Involvement of Serotonergic Mechanisms in the Disruption of Ovine Duodenal Migrating Myoelectric Complex Cycles by Duodenal Acidification

Infusions of 1 and 4 mmol of HCl (pH 2.0) into the duodenal bulb of conscious sheep, within 30% of the period of the migrating myoelectric complex (MMC) cycle, induced aborally propagated premature phases of regular spiking activity (RSA) on the proximal duodenum. A transient inhibition of reticular contractions and a shortening of the period of subsequent duodenal MMC cycles were obtained with infusions of 4 mmol of HCl but not with infusions of 1 mmol. When the animals were pretreated with the 5-hydrotryptamine (5-HT) antagonists, ritanserin (0.2 mg/kg) and metergoline (0.5 mg/kg), 15 min before duodenal infusions of 4 mmol of HCl, premature RSAs and inhibition of reticular contractions were still elicited, but shortening of the subsequent duodenal MMC cycles did not occur. It is concluded that the shortening of duodenal MMC cycles induced by duodenal infusions of 4 mmol of HCl involved a serotonergic mechanism incorporating 5-HT2 receptors. The premature duodenal RSA and inhibition of reticular motility also elicited by these infusions appeared to be independent of this serotonergic system.

Experimental and clinical results with proximal end-to-end duodenojejunostomy for pathologic duodenogastric reflux.

Existing Roux-en-Y bile diversion procedures for duodenogastric reflux coupled with distal gastric resection or antrectomy and vagotomy have varied success due to interruption of the physiologic relationships between stomach and duodenum, the reduction of the gastric reservoir, the side effects of vagotomy, and the effect of the Roux limb on gastric emptying. A new bile diversion procedure, suprapapillary Roux-en-Y duodenojejunostomy, was studied, which eliminates the need for gastric resection to prevent jejunal ulcers by preserving duodenal inhibition of gastric acid secretion and the protective effects of duodenal secretion on the surrounding mucosa. Experimentally, the incidence of jejunal ulceration was significantly decreased by the preservation of the proximal duodenum. Clinically, bile diversion by suprapapillary Roux-en-Y duodenojejunostomy alleviates symptoms of duodenogastric reflux disease without being ulcerogenic (in the presence of normal gastric secretion) or prolonging gastric emptying.

Effect of peptic digestion on emptying of cooked liver in dogs

By speeding the fragmentation of meat, peptic digestion might accelerate gastric emptying. To examine this possibility, mongrel dogs prepared with chronic duodenal fistulas were fed steak and 99mTc-labeled chicken liver. Measuring 99mTc in all chyme exiting from the stomach out the duodenal fistula allowed quantitation of the gastric emptying of 99MTc-liver. Emptying was studied during relatively uninhibited gastric propulsion (chyme diverted from the duodenum) or during inhibited gastric propulsion when the proximal bowel was perfused with chyme or fat. When chyme was diverted, the speed of emptying varied with peptic activity in the stomach—that is, it was increased by orogastric perfusion with acid-pepsin (vs. a control perfusion of pH 7 buffer) or, alternatively, was decreased from the unperfused stomach by i.v. cimetidine (vs. i.v. saline). By contrast, no effect of altering peptic conditions was observed when chyme was allowed access to the proximal bowel (the more normal situation), or when the duodenum was perfused with fat. We conclude that duodenal inhibition may override the effects of peptic digestion on the emptying of liver. We postulate that inhibition of gastric contractions limits the grinding of liver into particles susceptible to peptic digestion.

Gastroduodenostomy without vagotomy: Influence on basal gastric secretion in gastric fistula dogs

The influence of a gastroduodenostomy (GD) on basal gastric secretion was studied in six gastric fistula dogs. The volume, as well as the acidity, was increased in all the dogs and the basal gastric acid output thus rose by 455% ( P < 0.05). The rise in basal gastric secretion after GD may be caused partly by antral stimulation by bile reflux and partly by loss of stimulation of the duodenal inhibition mechanism.

On the Cause of the Increased Heidenhain Pouch Secretion and Serum Gastrin Concentration after Gastrojejunostomy in Dogs: With a statistical appendix

In 10 dogs with Heidenhain pouches (HP) a gastrojejunostomy (GEA) was constructed and later converted into a Roux en-Y anastomosis in order to abolish or reduce transstomal reflux. Next, duodenal inhibition was abolished by duodenal transection, and finally the duodenal bulb was excised. Twenty-four hour HP acid output increased after GEA, some 70% of the increase being attributable to transstomal reflux, the rest to decreased duodenal inhibition. Abolished duodenal inhibition caused a new rise, not significantly different from that caused by the combined effect of reflux and decreased duodenal inhibition after GEA. Twenty-four hour fasting HP acid output and 5 hr food-stimulated HP acid output rose after GEA by the same amount as that caused by abolished duodenal inhibition. A significant correlation was found between integrated gastrin and total HP acid output after food stimulation. Both fasting and food-stimulated gastrin concentration rose after GEA, the latter caused by reflux alone. Elimination of duodenal inhibition caused an unexpected rise in both fasting and food-stimulated gastrin concentration.

The Effect of Intragastric pH-Variations on the Gastric Acid Response to Insulin Hypoglycaemia in Healthy Subjects and Duodenal Ulcer Patients

The gastric acid response to i.v. injection of 0.15 U of soluble insulin/kg b.w. was determined in healthy subjects and duodenal ulcer patients during intragastric perfusion with water, 0.1 M HC1, and alkaline buffer (pH 8.3). Perfusion with hydrochloric acid significantly reduced the peak gastric acid output following insulin in 6 healthy subjects (reduction 45%, p less than 0.05) but had no significant effect on the peak gastric acid response to insulin in 7 DU patients (reduction 16%, p greater than 0.05). The 2.5-hour gastric acid response to insulin was, however, significantly reduced in both groups (56% and 35%, respectively) by exogenous acidification of the stomach. The gastric acid response to insulin hypoglycaemia in 3 DU patients was the same with intragastric water and alkaline buffer perfusion. The reduction of the gastric acid response to insulin hypoglycaemia by intragastric acidification corresponded to a reduced volume secretion and could not be ascribed to increased back diffusion of hydrogen ions or duodenal inhibition. These findings suggest that the gastric acid response to insulin hypoglycaemia is inhibited by a low intragastric pH in man, and that DU patients are less sensitive to the inhibitory mechanism than healthy subjects.

Influence of pancreatic secretion on gastric secretion in dogs.

Canine gastric secretion is significantly decreased after the intraduodenal administration of lyophilized pig pancreas, pancreatic juice and bovine trypsinogen. Conversely, intraduodenal administration of isotonic saline solution, lyophilized pig meat, trypsin and chymotrypsinogen failed to decrease gastric secretion in dogs. It is suggested that the pancreatic juice plays a role in the duodenal inhibition of gastric secretion through the trypsinogen activation peptide.

Duodenal inhibition of gastric secretion by osmotic agents in normal subjects and patients with duodenal ulcer

Gastric secretion in man is inhibited by the presence in the duodenum of hyperosmolar and hypoosmolar solutions. Both acid and pepsin outputs are affected. There is no change in hydrogen, sodium, or potassium ion concentration in the gastric juice. Pepsin concentration, however, is reduced by all inhibitory stimuli. Inhibition is thought to act directly upon parietal and chief cells, and a possible basis for this mechanism is discussed. The response is similar in control subjects and duodenal ulcer patients; there is in particular no evidence of impaired inhibition in the ulcer group. An anomalous feature is the relatively small inhibition of acid output after hypertonic saline in control subjects compared with the duodenal ulcer patients.

Duodenal inhibition of gastric secretion

The passage of the acid gastric contents into the duodenum causes an inhibition of gastric secretion. This inhibition is mediated in part at least by hormones. Pancreatic secretin and cholecystokinin have both been found to cause inhibition of food-stimulated secretion in Heidenhain pouches. Extirpation of the duodenum in whole or in part causes an increase in gastric secretion. Experimental operations such as the Exalto and Mann-Williamson procedures, which prevent the acid gastric content from entering the duodenum, cause an increase in gastric secretion through removal of the normal brake on gastric secretion exerted by the duodenum. The experimental ulcers produced by these operations are in part due to this hypersecretion. As pointed out by Poth, inadequacy of the duodenal brake on gastric secretion should be considered in relation to the cause of the hypersecretion of gastric juice in patients with ulcers. Clinical procedures such as gastroenterostomy with closure of the pylorus deviate the gastric acid from the duodenum and this is probably responsible for the disastrous results of this operation. The superiority of the Billroth I over the Billroth II operation is probably chiefly due to better preservation of the duodenal inhibition of gastric secretion.

Disparate pouch and main stomach secretions. Possible effect of antral and duodenal inhibition.

In 3 of 4 dogs, reduction by 60% of the parietal cell mass of the main stomach caused a significant increase in gastric juice output from an innervated pouch, while acid output was increased. Others' observations that vagotomy of the main stomach leads to enhanced denervated pouch secretion was confirmed. These findings are all best explained by reduction of antral and duodenal inhibition rather than vagotomy effects alone.

Chronic duodenal inhibition of the intestinal phase of gastric secretion.

Diversion of gastric contents away from the duodenum by means of gastrojejunostomy led to increases in Heidenhain pouch secretion in 8 dogs previously subjected to total antrectomy. It is suggested that acid in the duodenum may exert a chronic depressant effect on Heidenhain pouch secretion in the antrectomized dog.

MECHANISM OF DUODENAL INHIBITION OF GASTRIC SECRETION.

Pure gastric juice, as it is secreted by the fundus of the stomach, is an exceedingly corrosive liquid and has the capacity to digest away the normal mucous membrane of the stomach, duodenum, or small intestines and produce a defect indistinguishable from the chronic progressive peptic ulcers seen in patients.¹The mucous membrane is exposed to such pure gastric juice, either when gastric secretion is stimulated by agencies other than food or when an excessive secretion occurs, so that the buffering capacity of food, gastric mucus, swallowed saliva, and regurgitated secretions is overcome. Under normal conditions the mucosa is protected by these buffering agencies and also by an autoregulatory mechanism in the gastrointestinal tract itself. This mechanism provides for a stimulation of gastric secretion during food taking and a check of further secretion when sufficient gastric juice has been secreted to digest the food and before the gastric content

Inhibitory effects of hydrochloric acid in antrum and duodenum on histamine-stimulated gastric secretion in Pavlov and Heidenhain pouch dogs.

AbstractIn Pavlov and Heidenhain pouch dogs with excluded antrum and duodenum the effects of HCL instillations into those areas upon histamine‐stimulated gastric secretion were studied. It was found that acidification of the duodenum produced slight and irregular inhibition in some dogs, but no inhibition in others. These findings led the author to suggest that histamine‐stimulated gastric secretion is resistant to duodenal inhibition. Acidification of the antrum had no inhibitory influence on the secretion. No difference in susceptibility to antro‐duodenal inhibition was found between secretions from Pavlov and Heidenhain pouches.