Intraduodenal Acid Infusion Research Articles

Impact of intraduodenal acetic acid infusion on pancreatic duct cannulation during endoscopic retrograde cholangiopancreatography: A double-blind, randomized controlled trial.

Endoscopic retrograde cholangiopancreatography (ERCP) is associated with risk of complications. Methods to facilitate ductal cannulation may reduce complications. Intraduodenal acid infusion is a physiological approach to stimulate secretin release in human body and may facilitate cannulation. The objective of this study was to investigate the effect of intraduodenal acid infusion on pancreatic duct cannulation during ERCP. It was a single center, double-blind, randomized controlled trial. Consecutive patients undergoing first ERCP for pancreatic diseases were randomized toreceive 50mL acetic acid intraduodenal infusion at ERCP (acetic acid group) or 50mL saline (control group). The primary outcome, difficult cannulation rate (cannulation time >5min), in the two groups was compared. Two hundred ten patients were included in the final analysis (105 in each group). The difficult cannulation rate were 39.1% in the control group and 20.9% in the acetic acid group, and the difference was statistically significant (P=0.004). The overall successful deep cannulation rate was 89.5% and 85.7%, respectively (P=0.402). The cannulation time was remarkably shortened (182 vs 286s, P=0.018), and the cannulation attempts were significantly decreased (3.4 vs 4.4, P=0.008). The fluoroscopy time was also significantly reduced (60 vs 86s, P=0.028). The incidence of post-ERCP pancreatitis and hyperamylasemia was comparable (7.6% vs 10.5% and 10.5% vs 19.1%, P>0.05). Intraduodenal acetic acid infusion can significantly decrease difficult pancreatic cannulation rate, facilitate pancreatic duct cannulation, and reduce radiation exposure (ClinicalTrials.gov number, NCT02800772).

The effects of prostacyclin on canine hepatic bile flow.

The effect of prostacyclin on canine hepatic bile flow was evaluated. Utilizing chronic, unanesthetized bile fistula dogs, prostacyclin was found to significantly increase bile flow rates and bile bicarbonate and cyclic AMP concentration and output when compared to control values. The choleretic response was not due to the effect of the principal metabolic endproduct of prostacyclin, 6-keto-PGF1 alpha, as this substance increased bile flow but did not increase bicarbonate or cyclic AMP concentrations in bile. Prostacyclin did not increase [14C]erythritol clearance in bile suggesting that it stimulates bile duct secretion rather than the bile salt-independent fraction of canalicular bile. To ascertain if a relationship exists between the bicarbonate-rich choleresis produced by prostacyclin and that produced by secretin, the effects of prostacyclin and indomethacin on the choleresis produced by endogenous secretin stimulation were evaluated. During intraduodenal acid infusion, prostacyclin significantly increased bile flow. The increase was not secondary to increased secretin release as plasma secretin levels were not significantly changed from control levels. Prostaglandin synthetase inhibition by indomethacin administration did not alter the choleresis produced by intraduodenal acid. The prostacyclin-induced changes in bile flow were further evaluated in acute experiments in anesthetized dogs during which the effects of prostacyclin on systemic blood pressure, hepatic blood flow and cyclic AMP metabolism could be simultaneously determined. The choleresis produced by prostacyclin occurred in the presence of decreased systemic arterial blood pressure and hepatic blood flow. The increased bile cyclic AMP secretion produced by prostacyclin was not associated with increases in systemic or hepatogenous cyclic AMP. Prostacyclin increases canine bile flow and bicarbonate secretion, a process which may be mediated by cyclic AMP. The choleresis is not secondary to changes in hepatic blood flow or secretin release.

Effect of Somatostatin and Bombesin on Secretin-Stimulated Ductular Bile Flow in Dogs

The effects of somatostatin and bombesin on the choleresis produced by intraduodenal acid infusion were evaluated in dogs. Because of the documented effect of these agents on hormone release, serum gastrin and plasma secretin levels were monitored. Intraduodenal acid (12 mmol/h) increased bile flow and bile bicarbonate secretion and nearly doubled systemic plasma secretin levels. Bombesin significantly increased the bicarbonate-rich choleresis produced by intraduodenal acid and increased secretin release. Somatostatin inhibited completely the choleresis produced by 12 mmol/h of intraduodenal acid but did not significantly change systemic plasma secretin levels. Subsequent studies evaluated the effects of somatostatin (10 micrograms/kg . h) on bile flow and on systemic and portal plasma secretin concentrations stimulated by exogenous secretin administration and intraduodenal acid infusion. These studies demonstrated that somatostatin did not significantly change the choleretic response or the increases in plasma secretin produced by exogenous secretin. During duodenal acid infusion, somatostatin inhibited the choleresis and significantly decreased portal plasma secretin release. Evaluation of the relationship of the increase in bile flow to the increase in portal vein secretin concentrations, as well as comparison of the degree of inhibition of bile flow with the inhibition of secretin release produced by somatostatin, indicates that secretin produces approximately 80% of the choleresis produced by acid in the duodenum. Bombesin augments bile flow stimulated by infusion of acid into the duodenum by increasing secretin release, while somatostatin decreases bile flow produced by acid in the duodenum by directly inhibiting the release of secretin from the duodenal mucosa.

Secretin release in coeliac disease. Plasma secretin concentration and bicarbonate output to the duodenum after intraduodenal acid infusion in coeliac patients before and after treatment.

Infusion of 40 ml 0.1 mol/l HCl into the duodenum in eight untreated coeliac patients was followed by an increase of the plasma immunoreactive secretin (IRS) concentration from 1.6 +/- 0.2 pmol/l to a peak level of 2.4 +/- 0.3 pmol/l (p less than 0.05). After treatment with a gluten-free diet, the same patients showed an increase from 1.4 +/- 0.3 pmol/l to a peak level of 5.5 +/- 0.9 pmol/l after intraduodenal acid infusion, which was significantly higher than before treatment (p less than 0.01). In control subjects, intraduodenal acid infusion was followed by an increase from 1.4 +/- 0.2 pmol/l to 6.7 +/- 1.1 pmol/l, which was significantly higher than in untreated coeliac disease (p less than 0.01) but did not differ from what was found in treated coeliac patients. Significant differences in pH, volume, or bicarbonate content of the duodenal aspirates or the basal IRS levels were not found.

Physiological doses of secretin do not stimulate acute insulin release.

To study the effect of physiological increments in plasma secretin concentrations on basal and glucose-stimulated insulin release, bolus iv glucose injections (5 g) were given to normal weight volunteers (less than 108% ideal BW) before, during, and 30 min after a secretin infusion at a rate of 0.125 U/kg.h, raising mean plasma immunoreactive secretin to 35.5 +/- 8.3 pg/ml. Acute insulin responses to glucose were unaffected during or after the secretin infusion. Furthermore, when plasma glucose was elevated to postprandial levels (128--165 mg/dl), a similar secretin infusion also failed to alter acute insulin responses. In addition, no changes in basal glucose or insulin levels were found when endogenous secretin concentrations were increased by intraduodenal acid infusion. Thus, increases in plasma secretin to concentrations seen in the postprandial state fail to alter acute insulin secretion. It is unlikely that secretin plays any role in the intestinal stimulation of insulin secretion.

Effect of duodenal acidification on the lower esophageal sphincter pressure in the dog with special reference to related gastrointestinal hormones.

The role of the duodenum in the regulation of the lower esophageal sphincter pressure was studied in 3 anesthetized dogs with a duodenal fistula by relating the lower esophageal sphincter pressure with plasma gastrin and secretin level during intraduodenal acid infusion test. Instillation of hydrochloric acid into the duodenum produced an initial fall followed by a significant and sustained increase of the lower esophageal sphincter pressure. The initial fall of the lower esophageal sphincter pressure was found to correspond to a prompt but transient rise of plasma secretin concentration, while plasma gastrin did not change significantly throughout the experimental period. It is concluded that duodenum may be an important regulator of the lower esophageal sphincter pressure in the dog through secretin and other unknown factors.

Secretin secretion in patients with duodenal ulcer, chronic pancreatitis and diabetes mellitus.

Secretin releasing response to intraduodenal acid infusion was investigated in 15 cases of diseased control, 7 cases of duodenal ulcer, 5 cases of chronic pancreatitis, and 6 cases of diabetes mellitus. Plasma secretin levels in response to duodenal acidification were less in duodenal ulcer and the appearance of the maximal peak was delayed compared with that found in control. It is suggested that the secretin release was impaired in duodenal ulcer in spite of hypersecretion of gastric acids. In chronic pancreatitis, secretin releasing response to acidification was markedly impaired, in addition, inhibition of secretin release by bicarbonate was diminished due to a lack of bicarbonate flow from the pancreas. On the other hand, although the response of secretin release in diabetes mellitus was also lower compared with that in control group, the capacity of secretin response showed values in-between control subjects and chronic pancreatitis. This research was supported in part by grant from the Ministry of Education, Science and Culture in Japan.

Exogenous and endogenous secretin stimulation in the conscious rat.

The actions of intravenous secretin injection and of intraduodenal acid infusion were studied in conscious rats who had recovered from the operative procedure and were maintained at a normal body temperature. The basal secretion calculated per unit weight of pancreas was higher in the rat than in the dog, even when the basal endogenous secretin stimulation induced by gastric acid was suppressed by ligation of the pylorus. Intravenous injection of GIH secretin induced a dose-related increase in volume and bicarbonate outputs. A brief washing out of proteins occurred initially. The maximal secretory response to endogenous stimulation was less than after intravenous secretin injection. The rate of secretin release was the limiting factor of the endogenously stimulated secretion. Calculated per unit weight of gland, the maximal secretory response of the pancreas to secretin is smaller in the rat than in the dog.