Pentagastrin-stimulated Acid Output Research Articles

Suppression of gastric acid with intravenous esomeprazole and omeprazole: results of 3 studies in healthy subjects

To identify the optimal pharmacodynamic dosing regimen for esomeprazole administered intravenously (i.v.) and to compare acid suppression with various esomeprazole i.v. and omeprazole i.v. dosing regimens. A total of 90 healthy Helicobacter pylori-negative subjects participated in three randomized, crossover studies of esomeprazole i.v. Comparative acid output study: an open-label study that compared single 40 mg i.v. doses (administered over 30 min) of esomeprazole and omeprazole. Dose-ranging study: an open-label study that compared acid control with five different doses of esomeprazole i.v., administered over 24 h. Comparative pH study: a double-blind study that compared esomeprazole i.v. and omeprazole at doses of 80 mg (over 30 min) + 8 mg/h (for 23.5 h). In the comparative acid output study, estimated mean pentagastrin-stimulated acid output was reduced from 33.9 mmol/h at baseline to 5.4 mmol/h at 4 - 5.5 h with esomeprazole vs. 9.5 mmol/h with omeprazole (p < 0.001). In the dose-ranging study, the 80 + 8 mg/h regimen provided a greater mean time with pH > 6 (12.6 h) than the lower doses (11.0 and 10.7 h for 40 + 8 mg/h and 80 + 4 mg/h, respectively) and significantly more time with pH > 4 (21.5 vs. 19.7 and 19.2 h, respectively; p < 0.05). In the comparative pH study, the mean number of h with pH > 4 was similar between esomeprazole (21.4 h) and omeprazole (21.1 h). Esomeprazole was superior to omeprazole in reducing stimulated acid secretion. Control of intragastric pH was similar for esomeprazole and omeprazole at a dose of 80 + 8 mg/h. An esomeprazole i.v. dosage regimen of 80 + 8 mg/h appeared to be optimal for acid suppression in healthy subjects under study.

Comparison of Pentagastrin-Stimulated Maximum Acid Output in Patients with a History of Erosive Esophagitis Treated with 40 mg of Oral Pantoprazole Granules or Tablets

Comparison of Pentagastrin-Stimulated Maximum Acid Output in Patients with a History of Erosive Esophagitis Treated with 40 mg of Oral Pantoprazole Granules or Tablets

The value of corpus–antrum border determinations in highly selective vagotomy

Abstract In order to know whether the exact determination of the corpus–antrum border is of importance in highly selective vagotomy (HSV) the operation was performed on two matched groups of patients with duodenal ulcers. In group 1 (35 patients) HSV was performed using anatomical landmarks to define the distal extent of dissection. In group 2 (35 patients) HSV was performed using the same technique and then a gastrotomy was made and any remaining acid-secreting mucosa was identified using pH-metry under pentagastrin stimulation. In 22 cases secretion of acid was observed distal to the anatomically defined corpus-antrum border. In these patients afurther distal division of vagal branches was done until no acid secretion was observed. Two months and 1 year after the operation, basal acid output (BAO), pentagastrin-stimulated acid output (PAOpg), insulin-stimulated acid output (PAO1) and basal serum gastrin determinations were done and compared with the corresponding preoperative data. Our results show that despite the more extensive division of the antral vagal branches in group 2, BAO and PAOpg were similar in both groups postoperatively. Postoperative PAOI was also similar. Differences were observed, however, in postoperative serum gastrin levels–group 1 42.5 ± 6.0 pmol/l and group 281.7 ± 7.4 pmol/l 1 year after the operation. In no cases did the more extensive dissection of antral vagal branches lead to clinical or radiological gastric stasis. Thus, if the branches of the nerves of Latarjet are used as landmarks in performing HSV, in many cases vagally innervated, acid-secreting mucosa will be left in the stomach, but apparently this is quantitatively of minor importance. On the other hand, a more extensive distal vagal dissection leads to disturbingly high postoperative serum gastrin values.

Highly selective vagotomy without a drainage procedure in the treatment of duodenal ulcer.

Abstract A consecutive series of 25 patients with chronic duodenal ulcer has been treated by highly selective vagotomy without a drainage procedure. The vagal fibres passing to the distal 5–7 cm. of the stomach—the nerves of Latarjet—were left intact, as were the hepatic and coeliac branches of the vagus. The object was to denervate only the parietal cell mass, while preserving normal gastric emptying and normal inhibition of gastric secretion from the antrum and duodenum. This operation should cure the ulcer as effectively as vagotomy with drainage does, and at lower cost in terms of side-effects such as dumping and diarrhoea. The insulin test was negative in each case, suggesting that vagal denervation of the parietal cell mass was complete. Evidence provided by mucosal biopsies taken at operation does not fully support this view, however. Pentagastrin-stimulated acid output was reduced by 70 per cent, and pepsin output by 51 per cent, 3 months after operation. The volume of resting juice was halved and spontaneous acid output was reduced by 97 per cent at this time. Thus, highly selective vagotomy is as effective as truncal or bilateral selective vagotomy with drainage in reducing gastric acid output in the early months after operation. There have been no deaths. With 2 exceptions, the patients appear to be doing well clinically and few complain of side-effects, but the period of follow-up is only from 3 to 11 months. These results are encouraging. They suggest that a highly selective vagotomy, denervating the parietal cell mass but leaving the antrum innervated, may be all that is required to cure most patients who have a chronic duodenal ulcer.

The effect of antral denervation on gastric secretion in the dog.

Abstract The effect on gastric secretion of cutting the antral nerves was studied in dogs with a previous complete proximal gastric vagotomy, with an incomplete proximal gastric vagotomy and with otherwise intact vagi. There was no change in insulin- and pentagastrin-stimulated acid output in dogs with a previous vagotomy. The dog with otherwise intact vagi showed no change in insulin-stimulated acid output but there was a diminished acid response to low doses of pentagastrin. These results, if confirmed in man, would suggest that the antral vagal nerves have no clinically significant effect on gastric acid secretion.

Sham feeding for testing gastric secretory capacities before and after parietal cell vagotomy

The usefulness of acid secretory data collected during a modified sham-feeding (MSF) test was examined in 50 patients suffering from duodenal ulcer before and after parietal cell vagotomy. In these patients basal acid output pentagastrin-stimulated acid output and MSF-stimulated acid output were measured. Preoperative MSF-stimulated acid output was found to be correlated with preoperative basal acid output, and postoperative MSF-stimulated acid output was correlated with both preoperative basal acid output and postoperative basal and pentagastrin-stimulated acid outputs. The addition of preoperative MSF-stimulated acid output to preoperative pentagastrin-stimulated acid output did not noticeably increase the close relationship between the latter and postoperative pentagastrin-stimulated acid output. It is concluded that basal and MSF-stimulated secretory rates overlap. Therefore, it is suggested that in both preoperative and postoperative conditions the addition of the sham-feeding test to the more simple basal and pentagastrin-stimulated studies could be discarded.

Optimization of the in Vitro and in Vivo Properties of a Novel Series of 2,4,5-Trisubstituted Imidazoles as Potent Cholecystokinin-2 (CCK2) Antagonists

The systematic optimization of the structure of a novel 2,4,5-trisubstituted imidazole-based cholecystokinin-2 (CCK(2)) receptor antagonist afforded analogues with nanomolar receptor affinity. These compounds were now comparable in their potency to the bicyclic heteroaromatic-based compounds 5 (JB93182) and 6 (JB95008), from which the initial examples were designed using a field-point based molecular modeling approach. They were also orally active as judged by their inhibition of pentagastrin stimulated acid secretion in conscious dogs, in contrast to the bicyclic heteroaromatic-based compounds, which were ineffective because of biliary elimination. Increasing the hydrophilicity through replacement of a particular methylene group with an ether oxygen, as in 3-{[5-(adamantan-1-yloxymethyl)-2-cyclohexyl-1H-imidazole-4-carbonyl]amino}benzoic acid (53), had little effect on the receptor affinity but significantly increased the oral potency. Comparison of the plasma pharmacokinetics and the inhibition of pentagastrin-stimulated acid output following bolus intraduodenal administration of both 53 and 6 indicated that 53 was well absorbed, had a longer half-life, and was not subject to the elimination pathways of the earlier series.

Rebound acid hypersecretion after long‐term inhibition of gastric acid secretion

Rebound acid hypersecretion develops after the use of acid inhibitors. To estimate the duration of hypersecretion and to elucidate the role of the enterochromaffin-like (ECL) cell in rebound acid hypersecretion. Patients waiting for anti-reflux surgery who had used a proton pump inhibitor daily > 1 year were included. All patients discontinued taking acid inhibiting drugs after the operation. Basal and pentagastrin stimulated acid output was measured at 4, 8, 16 and 26 weeks postoperatively. Oxyntic mucosal biopsies were collected before and 26 weeks after the operation for counting of histidine decarboxylase (HDC) immunoreactive cells. Serum chromogranin A (CgA) and gastrin were measured before and at 4, 8, 16 and 26 weeks after the operation. Pentagastrin stimulated acid secretion was higher at 4 and 8 weeks than at 26 weeks after the operation. Gastrin and CgA were significantly reduced at 4 and 8 weeks, respectively. The number of HDC immunoreactive cells was reduced by 60% at 26 weeks postoperative. Rebound acid hypersecretion lasts more than 8 weeks, but less than 26 weeks after long-term proton pump inhibition. The findings indicate that not only the parietal cell mass, but also ECL cell mass and activity are involved in the mechanism of acid hypersecretion.

ESOMEPRAZOLE 40 MG ADMINISTERED INTRAVENOUSLY (I.V.) PROVIDES BETTER CONTROL OF BASAL AND STIMULATED GASTRIC ACID SECRETION THAN OMEPRAZOLE 40 MG ADMINISTERED I.V.

Purpose: This study compared the effect on basal and pentagastrin stimulated acid output (BAO and PAO) of single-dose i.v. administration of esomeprazole 40 mg and omeprazole 40 mg. Methods: This was an open, randomized, two-way cross-over study in 23 Helicobacter pylori-negative healthy male and female subjects (18 males; mean age: 26 years; mean body mass index: 22.8 kg/m). Both drugs were administered as single 30-minute i.v. infusions with a washout period of at least 6 days. BAO (1 h) and PAO (1.5 hrs) were determined at baseline, between 3–5.5 h and finally between 23–25.5 h after drug administration on each study day. Blood samples, taken during the first 12 hours, were used to determine the area under the plasma concentration-time curve (AUC) and maximum observed plasma concentration (Cmax) for both drugs. The PAO and BAO values were analyzed using a mixed model ANOVA. The mean for each treatment and the mean treatment difference were estimated with 95% confidence intervals (CI). As an interim analysis was performed when 12 subjects had been included in the study, a 97.5% CI was calculated for the mean difference in PAO measured 3-5.5 hours after dose. Results: At baseline the mean BAO and PAO were 4.4 mmol/h (95% CI: 3.0 to 5.8) and 34.0 mmol/h (95% CI: 30.2 to 37.2), respectively. Intravenous administration of esomeprazole 40 mg resulted in a more pronounced reduction in BAO and PAO both measured 3–5.5 h and 23–25.5 h after dose compared with omeprazole 40 mg i.v. (Table). The geometric mean AUC and Cmax values were 36% and 18% higher, respectively, for esomeprazole 40 mg i.v. compared with omeprazole 40 mg i.v. There were no serious adverse events and both drugs were well tolerated.Table: Basal and pentagastrin stimulated acid output (BAO, PAO).Conclusions: Esomeprazole 40 mg i.v. provides faster and more complete control of basal and stimulated gastric acid secretion throughout the 24-hour period than omeprazole 40 mg i.v.

INTRAVENOUS LANSOPRAZOLE IS EQUIVALENT TO ORAL CAPSULE IN SUPPRESSING PENTAGASTRIN-STIMULATED ACID OUTPUT

Purpose: Patients with erosive esophagitis (EE) may require short-term intravenous therapy due to their inability to receive medication orally. The purpose of this multicenter, open-label study was to compare the pharma-codynamics of 30 mg intravenous lansoprazole (IV LAN) to 30 mg oral lansoprazole (PO LAN) capsules in patients with EE. Methods:H. pylori–negative patients with >= Grade 2 EE confirmed by endoscopy received 30 mg PO LAN for 7 consecutive days followed by 30 mg IV LAN infused over 30 min for 7 consecutive days without a washout. In both periods, LAN was administered 1 hr prior to the morning meal. Pentagastrin-stimulated acid output (MAO) and basal acid output (BAO) were assessed 22 hrs and 21 hrs, respectively following the last dose of PO LAN (Day 8), first dose of IV LAN (Day 9) and last dose of IV LAN (Post-Treatment Day 1). The primary endpoint was MAO after the last dose of IV LAN as compared to that afterthe last dose of PO LAN. Secondary endpoints included BAO after the last dose of IV LAN as compared to that after the last dose of PO LAN. Therapeutic equivalence of the two formulations was established if the population average for IV LAN minus 120% of PO LAN was negative. To test the null hypothesis of IV-1.2 PO> = 0, one-sided Wilcoxon signed-rank tests were performed at a significance level of 0.05. Equivalence would be established by rejection of the null hypothesis. Safety was monitored by adverse events, vital signs, physical examinations, routine ophthalmic examinations, laboratory evaluations, electrocardiograms and IV infusion site assessments. Results: 68 subjects 19 to 72 yrs of age enrolled, including 51 males and 17 females; among them 57 received 7 doses of IV LAN as well as at least 7 doses of PO LAN. The median MAO (mEq/hr) was 7.72 on Day 8 and 7.25 on Post-Treatment Day 1. The median BAO (mEq/hr) was 0.73 on Day 8 and 0.45 on Post-Treatment Day 1. Equivalence of the two formulations was established for both MAO (p = 0.001, N = 56) and BAO (p = 0.011, N = 57). All adverse events were mild or moderate in severity. Both formulations were safe and well tolerated. Conclusions: This study confirms previous findings that IV lansoprazole is as effective at suppressing pentagastrin-stimulated acid output and as safe as the oral formulation in treating patients with EE. The IV formulation is an alternative for the short-term treatment in patients who are unable to take oral medication.

Intravenous lansoprazole: in erosive oesophagitis.

An intravenous formulation of lansoprazole, a proton pump inhibitor, is approved for use in patients with erosive oesophagitis who are temporarily unable to take oral lansoprazole. In healthy volunteers, oral and intravenous lansoprazole 30 mg/day were equivalent in suppressing basal and pentagastrin-stimulated maximum gastric acid output. Moreover, the mean 24-hour intragastric pH did not differ significantly following oral or intravenous administration of lansoprazole and was significantly higher with both formulations than with intravenous polyethylene glycol vehicle. After treatment for 7 days in patients with erosive oesophagitis, intravenous lansoprazole (30 mg/day) recipients had significantly lower median stimulated and basal gastric acid output measurements than placebo recipients. Median pentagastrin-stimulated gastric acid output levels were equivalent after 7 days treatment with intravenous or oral lansoprazole. Intravenous lansoprazole is generally well tolerated. All adverse events experienced by patients with erosive oesophagitis who received intravenous lansoprazole were mild or moderate in severity.

Gender-related differences in pentagastrin-stimulated gastric acid output in proton pump inhibitor-treated subjects

Gender-related differences in pentagastrin-stimulated gastric acid output in proton pump inhibitor-treated subjects

Gender-Related Differences in Pentagastrin-Stimulated Gastric Acid Output in Proton Pump Inhibitor-Treated Subjects

Gender-Related Differences in Pentagastrin-Stimulated Gastric Acid Output in Proton Pump Inhibitor-Treated Subjects

Presence of gastric autoantibodies impairs gastric secretory function in patients with Helicobacter pylori-positive duodenal ulcer.

Although the association between Helicobacter pylori infection and gastric autoimmunity is now well established, to date little is known about the significance of anticanalicular autoantibodies in patients with duodenal ulcer (DU). We therefore investigated the prevalence of serum antiparietal cell autoreactivity in DU patients as well as the relationship between these autoantibodies, gastric histopathology and gastric secretory function in this setting. Forty-one consecutive patients with H. pylori-positive DU were initially recruited. In all patients, basal (BAO) and pentagastrin stimulated acid output (PAO), fasting and meal-induced serum gastrin levels, as well as serum pepsinogen I concentrations, were measured. Antral and body gastritis was evaluated according to the Sydney system. Serum anticanalicular autoreactivity was determined by the indirect immunoperoxidase technique. Serum anticanalicular autoantibodies were found in 7 out of 34 patients (20%). The presence of these antibodies was associated with a significantly higher grade of body gastritis (activity: 1.9 versus 0.9) as well as with significantly higher fasting and meal stimulated gastrin levels (mean fasting gastrin, 76.4 (15.2) microg/ml versus 59.3 (20.5) microg/ml). In addition, PAO values were significantly lower in patients with gastric autoantibodies than in those without this autoreactivity (mean 0.35 (0.16) mmol kg(-1)h(-1) versus 0.49 (0.16)mmol kg(-1)h(-1)). In contrast, no significant differences were found between patients with and without anticanalicular autoantibodies as regards fasting serum pepsinogen I concentrations. Serum anticanalicular autoantibodies can be detected in 20% of patients with DU and are associated with a more severe pattern of body gastritis, higher gastrin levels and decreased peak acid secretion values. Their presence could account for the normal or reduced acid output which can be seen in a subset of DU patients.

Helicobacter pylori infection in the cat: evaluation of gastric colonization, inflammation and function.

Further elucidation of the consequences of Helicobacter pylori infection on gastric mucosal inflammation and gastric secretory function would be facilitated by an animal model that is susceptible to infection with H. pylori, is broadly similar in gastric physiology and pathology to people, and is amenable to repeated non-invasive evaluation. The goal of this study was to examine the interrelationship of bacterial colonization, mucosal inflammation and gastric secretory function in cats with naturally acquired H. pylori infection. Twenty clinically healthy cats with naturally acquired H. pylori infection (cagA-, picB) and 19 Helicobacter-free cats were evaluated. Gastric colonization was determined by tissue urease activity, light microscopy, culture and PCR. The mucosal inflammatory response was evaluated by light microscopy, and by RT-PCR of the pro-inflammatory cytokines IL-1alpha, IL-1beta, IL-8 and TNF-alpha in gastric mucosa. Gastric secretory function was assessed by measuring pentagastrin-stimulated acid secretion, fasting plasma gastrin, and antral mucosal gastrin and somatostatin immunoreactivity. H. pylori colonized the pylorus, fundus and cardia in similar density. Bacteria were observed free in the lumen of gastric glands and were also tightly adherent to epithelial cells where they were associated with microvillus effacement. Mononuclear inflammation, lymphoid follicle hyperplasia, atrophy and fibrosis were observed primarily in H. pylori-infected cats, with the pylorus most severely affected. Neutrophilic and eosinophilic infiltrates, epithelial dysplasia, and up-regulation of mucosal IL-1beta and IL-8 were observed solely in infected cats. Fasting plasma gastrin concentrations and pentagastrin-stimulated acid output were similar in both infected and uninfected cats. There was no relationship of bacterial colonization density or gastric inflammation to plasma gastrin concentrations or gastric acid output. The pattern of colonization and the mucosal inflammatory response in cats with naturally acquired H. pylori are broadly similar to those in infected people, particularly children, and non-human primates. The upregulation of IL-8 in infected cats was independent of cagA and picB. Our findings argue against a direct acid-suppressing effect of H. pylori on the gastric secretory-axis in chronically infected cats.

Presence of Gastric Autoantibodies Impairs Gastric Secretory Function in Patients with Helicobacter pylori-positive Duodenal Ulcer

Background: Although the association between Helicobacter pylori infection and gastric autoimmunity is now well established, to date little is known about the significance of anticanalicular autoantibodies in patients with duodenal ulcer (DU). We therefore investigated the prevalence of serum antiparietal cell autoreactivity in DU patients as well as the relationship between these autoantibodies, gastric histopathology and gastric secretory function in this setting. Methods: Forty-one consecutive patients with H. pylori-positive DU were initially recruited. In all patients, basal (BAO) and pentagastrin stimulated acid output (PAO), fasting and meal-induced serum gastrin levels, as well as serum pepsinogen I concentrations, were measured. Antral and body gastritis was evaluated according to the Sydney system. Serum anticanalicular autoreactivity was determined by the indirect immunoperoxidase technique. Results: Serum anticanalicular autoantibodies were found in 7 out of 34 patients (20%). The presence of these antibodies was associated with a significantly higher grade of body gastritis (activity: 1.9 versus 0.9) as well as with significantly higher fasting and meal stimulated gastrin levels (mean fasting gastrin, 76.4 (15.2) pg/ml versus 59.3 (20.5) pg/ml). In addition, PAO values were significantly lower in patients with gastric autoantibodies than in those without this autoreactivity (mean 0.35 (0.16) mmol kg-1 h-1 versus 0.49 (0.16) mmol kg-1 h-1). In contrast, no significant differences were found between patients with and without anticanalicular autoantibodies as regards fasting serum pepsinogen I concentrations. Conclusions: Serum anticanalicular autoantibodies can be detected in 20% of patients with DU and are associated with a more severe pattern of body gastritis, higher gastrin levels and decreased peak acid secretion values. Their presence could account for the normal or reduced acid output which can be seen in a subset of DU patients.

Hypersecretory duodenal ulcer and Helicobacter pylori infection: for-year follow-up study

Background. About 10% of duodenal ulcer patients are characterized by gastric acid hypersecretion with normal gastrin values. Relapsing duodenal ulcer after Helicobacter pylori cure has been related to high acid output and maintenance antisecretory therapy has been suggested in hypersecretory duodenal ulcer patients. The role of Helicobacter pylori infection and the effects of Helicobacter pylori cure in hypersecretory duodenal ulcer patients still remain to be fully studied. Aim. To study: a) whether gastric acid hypersecretion “per se” is a risk factor for duodenal ulcer recurrence; b) whether maintenance antisecretory therapy is necessary after eradication in hypersecretory duodenal ulcer patients. Patients. The study population comprised 8 hypersecretory duodenal ulcer patients, selected from a population of 79 Helicobacter pylori-positive duodenal ulcer patients. Methods. Hypersecretory duodenal ulcer patients were followed-up for at least 4 years after eradication. Gastric acid secretion was measured again 12 months after Helicobacter pylori eradication. Gastroscopy with histology was performed 3, 6, 12 and 36 months after treatment, 13C-urea breath test after 42 months; clinical questionnaires were completed every 6 months. Results. After eradication, despite a not significantly reduced high acid output (median value of basal acid output and pentagastrin-stimulated acid output, respectively, 23.1 mEg/h and 64. 1 mEg/h before treatment vs 16 mEg/h and 49.7 mEq/h 12 months after treatment), all patients were free from symptoms, none of them had duodenal ulcer relapse or complications ( 7 8 before treatment), or needed antisecretory maintenance therapy, except for one patient taking non-steroidal anti-inflammatory drugs. Conclusions. These findings, obtained in a selected population of hypersecretory duodenal ulcer patients with long-term follow-up, suggest that after successful Helicobacter pylori eradication gastric acid hypersecretion “per se” is not able to determine the recurrence of duodenal ulcer.

Effects of Helicobacter pylori gastritis on gastric secretion in healthy human beings.

Helicobacter pylori gastritis is common, but effects on gastric secretion are not well understood. We measured basal and pentagastrin-stimulated gastric acidity, pepsin activity, and fluid output, as well as serum gastrin concentrations and H. pylori antibody levels, before and after treatment of H. pylori gastritis in 28 men and women. Subjects were studied before and 1 and 3 mo after a course of bismuth, metronidazole, and tetracycline. Elimination of H. pylori gastritis, accomplished in 14 subjects, increased basal and pentagastrin-stimulated gastric acidity (by 15 meq/l) and basal acid output significantly (by 2.1 meq/h 1 mo after therapy). Elimination of H. pylori had an opposite effect on pepsin secretion, significantly decreasing pepsin output by 30%. Elimination of H. pylori significantly reduced nonparietal fluid output by 35%, without affecting fluid output from parietal cells. Serum gastrin and H. pylori antibody levels declined significantly after elimination of H. pylori. None of these changes was observed in 14 subjects whose H. pylori gastritis was resistant to antimicrobial therapy. In summary, eradication of H. pylori infection increases gastric acidity by reducing nonparietal gastric secretion from peptic and other cells.

The effect of acute bilateral adrenalectomy on serotonin-induced inhibition of gastric acid secretion and acute gastric mucosal injury in rats.

Serotonin (5-hydroxytryptamine, 5-HT) produces many changes in gastric functional parameters, including the inhibition of gastric acid secretion and changes in mucosal blood flow. Exogenous 5-HT has also been shown to induce gastric erosion. The influence of adrenalectomy on experimental lesions in the rat gastric mucosa remains controversial. The aim of this study was to see the effects of adrenalectomy on pentagastrin stimulated gastric acid secretion in anaesthetized male Wistar rats. Gastric acid was collected via cannulae placed in the stomach. 5-HT (3.5 mumol/kg, i.v.) inhibited pentagastrin stimulated acid output by 54% and produced haemorrhagic gastric lesions with a mean ulcer index of 2 +/- 0.3. Adrenalectomy prevented both 5-HT induced inhibition of gastric acid secretion and mucosal injury. The results suggest that the effects of 5-HT require an intact adrenal gland.

Effects of aging and gastritis on gastric acid and pepsin secretion in humans: A prospective study

BACKGROUND & AIMS: Recent studies suggesting that gastric secretion does not decrease with aging included few elderly individuals and measured only acid secretion. The aims of this study were to measure gastric acid and pepsin output in 206 health Americans (age range, 18- 98 years) and to compare secretion rates with gastric histology. METHODS: Immediately after basal and pentagastrin-stimulated acid and pepsin outputs were measured, oxyntic biopsy samples were obtained. RESULTS: Gastric acid and pepsin output rates were similar in young (age range, 18-34 years) and middle-aged (age range, 35-64 years) groups. Stimulated acid output was reduced approximately 30% in the elderly (age range, 65-98 years). However, after adjustment for histology, Helicobacter pylori infection, and other variables, age had no independent effect on acid output. The decline in acid secretion in the elderly was primarily related to a higher prevalence of chronic atrophic gastritis and a lower prevalence of smoking. Pepsin output was reduced by approximately 40% in the elderly. After adjustment for other variables, age remained a robust predictor of reduced pepsin output. CONCLUSION: Although advancing age has no independent effect on gastric acid secretion, it is associated with reduced pepsin output independent of atrophic gastritis, H. pylori infection, and smoking. (Gastroenterology 1996 Apr;110(4):1043-52)