The Origin of Nocturnal Intragastric pH Rises in Healthy Subjects

Background: Duodenogastric reflux (DGR) can produce transient increases in gastric luminal pH. It has been proposed that intragastric pH-metry is a reliable method for the detection of DGR. Our aim was to test the hypothesis that nocturnal increases in antral pH are due solely to DGR. Methods: Gastric pH was monitored overnight using two glass pH electrodes, one in the antrum adjacent to the tip of a nasogastric tube and one in the corpus. Scheduled antral aspirations were performed hourly to determine base-line concentrations of total bile acids (TBA; a marker of DGR) and thiocyanate (SCN; a marker of swallowed saliva). Additional, triggered aspirations were performed if antral pH exceeded 3.0 for 1 min or more (PHAP; period of high antral pH). TBA and SCN were considered to be increased if they exceeded the 90th percentile of values determined in scheduled aspirates (TBA, 0.88 mM; SCN, 0.67 mM). Results: In 28 of the 62 samples whose aspiration was triggered by a PHAP the pH was less than 3.0, and the sample was not considered to be representative. In the remaining 34 samples the antral luminal pH and the sample pH were concordant; TBA alone was increased in 6 samples, SCN alone was increased in 6 samples, and TBA and SCN were both increased in another 3 samples. Thus, DGR and swallowed saliva alone or in combination accounted for only 15 (45%) of the PHAP in which adequate gastric samples were obtained. Conclusion: Samples of gastric antral contents often do not reflect accurately the acidity of gastric fluid in contact with a luminal antral pH electrode. Nocturnal increases in antral pH, detected by a luminal electrode, are frequently due to mechanisms other than duodenogastric reflux or swallowed saliva. Thus, antral pH-metry is not suitable for monitoring the occurrence of duodenogastric reflux.     

Studies of luminal and mucosal pH in reflux esophagitis and antral gastritis.

Luminal and mucosal pH were measured endoscopically in patients with reflux esophagitis and antral gastritis and in control subjects. In all subjects, significant lumen-to-mucosa gradients were observed in the esophagus, stomach and acidified proximal duodenum. In the reflux patients luminal pH was lower in the fundus (mean +/- SEM, control vs. reflux esophagitis: 2.01 +/- 0.17 vs. 1.32 +/- 0.18; p less than 0.02) and antrum (3.51 +/- 0.35 vs. 2.13 +/- 0.24; p less than 0.01) and, in the gastritis patients, in the fundus (2.01 +/- 0.17 vs. 1.3 +/- 0.17; p less than 0.02). In both patient groups, mucosal pH was lower in the fundus (control vs. reflux vs. gastritis: 4.84 +/- 0.37 vs. 3.37 +/- 0.61 vs. 3.12 +/- 0.6; p less than 0.05) and acidified duodenal cap (6.74 +/- 0.13 vs. 6.09 +/- 0.24 vs. 5.73 +/- 0.46; p less than 0.03). Mucosal pH profiles at the various sites showed less resistance of the gradient to a highly acidic environment in both the lower esophagus and antrum than in fundus and duodenum, and this was the case in the patient and control groups. Though associated with a more acid environment, neither esophagitis nor antral gastritis exhibits a specific deficit in the 'mucus-bicarbonate barrier', suggesting that the pathogenesis of these disorders may depend more on abnormal 'attack' rather than impaired defense.     

Profound increase ofHelicobacter pylori urease activity in gastric antral mucosa at low pH

The effect of pH onH. pylori urease activity in its ecological niche was studied in gastric antral biopsy specimens. Specimens were incubated in 10 mmol/liter urea solutions at pH range 3.3–8.2. Activity of urease was studied by measuring production of ammonia and change in pH of the solutions. Urease activity was reduced at pH 8.2 (1424 ± 218 µmol/liter) but decreasing initial pH to neutral and acidic values resulted in significant maximal 6.5-fold increase in ammonia production (9491 ± 1073 µmol/liter,P<0.0005), which considerably raised the pH of the test solutions. Peak urease activity was between pH 5.0 and 7.0. In contrast to specimens incubated initially at pH 8.0, reincubation of washed specimens from solutions with initial pH 7.0 showed eightfold decreased urease activity. It is concluded that urease activity is markedly pH dependent with pH optima below the physiological mucosal surface pH. Furthermore, availability of urease is limited. Thus, an impaired gastric mucosal integrity allowing back diffusion of hydrogen ions may release urease activity, which might further weaken the mucus barrier and damage the gastric epithelium.This study was supported by the Deutsche Forschungsgemeinschaft (Mi 190/3).     

Determinants of oesophageal 'alkaline' pH environment in controls and patients with gastro-oesophageal reflux disease.

The determinants of the oesophageal alkaline pH environment are poorly understood. Saliva (pH 6.4-7.8) may be a major contributor, although some argue the importance of refluxed alkaline duodenal contents. Acid and alkaline reflux parameters were studied over 2 days in 30 subjects (control, oesophagitis and Barrett's patients; 10 each) using glass pH electrodes. In phase 1, one pH electrode was placed 1 cm below the upper oesophageal sphincter to assess the influence of saliva and the other 5 cm above the lower oesophageal sphincter. Phase 2 was identical except that one pH probe was 5 cm below the lower oesophageal sphincter to record duodenogastric reflux. Patient groups spent, on average, 50 fold more time during the upright and supine periods at acidic pH than controls. Saliva was responsible for the percentage of time the pH > 7 and contributed significantly to the percentage of time the pH > 6 in both the proximal and distal oesophagus of control subjects, as shown by an absence of pH > 7 and a significant (p < 0.001) fourfold decrease in pH > 6 during sleep. A similar pattern was seen in the proximal oesophagus of both reflux groups. The reflux and Barrett's patients, however did not show a significant decrease in the percentage of time the pH > 6 at night in the distal oesophagus suggesting a relative increase in 'alkaline' exposure from another source. This was not because of duodenogastric reflux as the corresponding pH rises in the fundus of the stomach were non-existent. Although this was not studied specifically, it is believed to be a protective meachanism, the result of alkaline secretion produced by submucosal oesophageal glands.     

Indications for 24-hour gastric pH monitoring with single and multiple probes in clinical research and practice

The methodology of prolonged gastric pH monitoring has not yet been standardized with regard to the number and position of pH probes. Twenty-seven healthy volunteers and 11 patients affected by nonulcer dyspepsia have been submitted to 24-hr ambulatory simultaneous pH monitoring of the distal esophagus, fundus, and antrum. Fundic and antral pH profiles have been compared and causes of pH variations (pH>4) identified. Both in healthy volunteers and dyspeptic patients, percentile curves of fundic and antral pH were statistically different in more than one of the daily periods considered (24-hr, postprandial, interdigestive, nocturnal). Percent time of duodenogastric reflux is significantly higher in the antrum than in the fundus in both groups. Modalities of gastric alkalinization secondary to food or duodenogastric reflux were different for the fundus and for the antrum both in healthy and dyspeptic subjects and between the two groups. These differences suggest that single and multiple pH monitoring of the stomach have different indications, and the position of the probes should vary according to the purpose of the test.     

Long-term ambulatory gastric pH monitoring: validation of a new method and effect of H2-antagonists

A new ambulatory monitoring system was evaluated for long-term measurements of gastric acidity. A close correlation was observed between values indicated by the pH electrode of the system and the pH of simultaneously aspirated gastric juice, suggesting that the electrode signaled the pH of the gastric fluid content. When the pH electrode was passed via an endoscope, and its bulb was placed against the corpus mucosa, a higher acidity was recorded as compared with gastric juice. To test whether the electrodes measured mucosal pH during ordinary test conditions, the readings of pH probes with mechanically shielded bulbs that did not come into direct contact with the mucosa were compared with those of nonshielded probes in identical positions. Similar results were observed, supporting the hypothesis that nonshielded probes measured the pH of gastric contents rather than that of the mucosa. The importance of a standardized electrode position and a fixed meal schedule was demonstrated in simultaneous recordings of antral and fundic pH. Under fasting conditions, acidity was similar in both regions. After ingestion of a meal, gastric contents were more alkaline in the fundus than in the antrum. A wide range of 24-h acidity (19-83 mmol/L) was detected in 25 healthy subjects. The day-to-day reproducibility of the method as revealed in two consecutive 24-h tests was good. The effect of cimetidine and ranitidine on gastric acidity was evaluated in 9 subjects in a double-blind, double-dummy trial. Mean 24-h H+ activity was 37.4 +/- 4.6 mmol/L under placebo medication. It was lower with cimetidine, two doses of 400 mg (23.8 +/- 4.0); cimetidine, four doses of 400 mg (10.2 +/- 3.0); ranitidine, two doses of 150 mg (10.3 +/- 3.6), and two doses of 300 mg (10.0 +/- 3.5), respectively. In conclusion, ambulatory long-term pH monitoring is a suitable method to assess the physiologic pattern of gastric acidity and the effect of antisecretory drugs.     

The effect of intragastric neutralization on the gastric acid response to antral distension in man.

The gastric acid secretion in response to graded antral distension was determined in healthy subjects and in peptic ulcer patients with water perfusion or alkaline buffer perfusion of the stomach, giving an intragastric pH of 1.8-3.0 and 6.2-8.3 respectively. Intragastric neutralization increased the basal acid secretion in healthy subjects and gastric ulcer patients but did not change the basal acid secretion in duodenal ulcer patients. Distension of the antrum produced the same secretory effect with and without intragastric neutralization: no increased acid response in healthy subjects, a slight acid response in patients with a quiescent duodenal ulcer or a gastric ulcer, and a more pronounced acid response in patients with an active ulcer, amounting to about 30% of the peak acid response to pentagastrin. The results show that: a) the peptic ulcer patients - and particularly patients with an active duodenal ulcer - are more sensitive to the acid secretory effect of antral distension than healthy subjects; b) increasing the intragastric pH above 20 does not enhance the acid response to antral distension; c) the acid secretory effect of antral distension is markedly less in man than the effect observed in the dog.     

In vitro protection of amphibian gastric mucosa by nutrient HCO3- against aspirin injury

The effects of luminal aspirin [acetylsalicylic acid (ASA)] at luminal pH 4.5 and pH 3.0 on Ussing chambered amphibian gastric fundic and antral mucosae were investigated using different concentrations of HCO3- ([HCO3-]) in the nutrient solution in histamine-stimulated or metiamide-treated tissues. The severe surface cell and oxyntic gland injury seen in histamine-stimulated tissues after a 3-h exposure to 20 mM ASA at luminal pH 4.5 in HCO3- -free nutrient solution (HEPES) was prevented by including 18 mM or 48 mM HCO3- in the nutrient solution. At luminal pH 3.0, 48 mM HCO3- in the nutrient solution delayed the histologic damage to the surface epithelium and oxyntic glands caused by a 30-min exposure to 20 mM luminal ASA, but it afforded no protection to a 60-min exposure. This protection of the gastric epithelium by a high nutrient [HCO3-] did not occur in metiamide-treated tissues at luminal pH 3.0. Although the injury to antral epithelial cells exposed to 20 mM luminal ASA at luminal pH 3.0 or 4.5 was less severe than that in fundic mucosae, 48 mM HCO3- in the nutrient solution also afforded clear protection in this tissue. A high nutrient [HCO3-] prevented the sharp fall in the potential difference observed in fundus exposed to ASA at luminal pH 4.5 and delayed the fall in potential difference observed in fundic and antral mucosae exposed to ASA at luminal pH 3.0. The high nutrient [HCO3-] did not prevent the increase in resistance observed in tissues during ASA exposure at luminal pH 4.5 and 3.0. The electrical data reflect not only the damaged surface and oxyntic cells caused by ASA, but also the complex effects of ASA on active and passive ion transport. We conclude the following: (a) The mucosal injury to the fundus and antrum caused by luminal ASA is prevented by 48 mM HCO3- in the nutrient solution when luminal pH is 3.0 and by 18 mM HCO3- when luminal pH is 4.5. Absence of nutrient HCO3- accentuates the injury caused by luminal ASA. (b) The luminal pH, concentration, and time of exposure influence the depth and severity of ASA injury to the fundic and antral mucosa. (c) The electrophysiologic and morphologic changes after ASA exposure are not interrelated, due to the complex effects of ASA on the ion transport and morphology of the gastric epithelium.     

Ontogeny of gastrin, somatostatin, and the H+/K(+)-ATPase in the ovine fetus.

In the term human and ovine fetus, plasma gastrin is elevated, but gastric acid secretion is below adult levels, suggesting a developmentally related immaturity in gastrin and gastric acid regulation. This study investigated a number of elements of the gastric acid regulatory system: gastrin and its glycine-extended precursor, somatostatin, and the H+/K(+)-ATPase. Measurements were made in blood, antrum, and fundus of the ovine fetus during the last half of gestation, of 15-day-old lambs, and of adult sheep at the level of mRNA synthesis, tissue storage, and secretion. Plasma amidated gastrin (gastrin-amide) was elevated at or above adult values from 125 days (term is 145 days) and steadily increased with development, peaking in the lamb. Similar changes occurred with plasma glycine-extended gastrin (gastrin-gly). The peak concentration of antral gastrin-amide was present in the lamb, while the maximum antral gastrin-gly level occurred 1 week before birth. Gastrin mRNA paralleled the changes in antral gastrin-gly. The proportion of higher mol wt species of gastrin decreased during gestation in both plasma and antrum. Low amounts of mRNA for the H+/K(+)-ATPase was present from at least 120 days of gestation and antedated gastric acid secretion. However, there was a 3-fold increase in H+/K(+)-ATPase mRNA from the 140-day-old fetus to the lamb, the period when the greatest reduction in gastric pH occurred (pH 5 to 2). Antral and fundic somatostatin increased rapidly in the fetus at 120 days gestation and were above adult values at term and in the lamb. Somatostatin mRNA changed in parallel to somatostatin peptide. Somatostatin-14 was the major species in antrum and fundus throughout development. The increase in circulating and antral gastrin-amide after birth may be the result of increased amidation of gastrin-gly as well as increased expression of gastrin mRNA. Amidation of gastrin may be a regulatory step in the production of biologically active gastrin during development. The major increase in gastrin and the H+/K(+)-ATPase that occurs in the week before and after gestation correlated with the onset of increased gastric acidity.     

Gastroduodenal mucosal surface and luminal pH in gastric ulcer

Gastroduodenal mucosal surface pH was measuredin situ by electrode in endoscopically normal and gastric ulcer patients. With the exception of the antrum, mucosal surface pH in the ulcer group (GU) resembled that of the endoscopically normal group. In contrast, the antral mucosal surface pH of the GU group of 7.06±0.11 (22) was significantly (P<0.001) higher than that of 5.46±0.36 (34) for the endoscopically normal group. This difference was also evident when comparison was restricted to subjects in both groups having a fundal luminal fluid pH of less than 3. When the fundal luminal pH was below pH 3, antral mucosal surface pH was 4.79±0.41 (24) in endoscopically normal subjects and significantly less (P<0.001) than the value of 6.98±0.18 (12) for gastric ulcer patients. Mucosal surface alkalinity of the GU antrum may be a response to damage but seems inappropriate in view of the likelihood of acid dependent inhibition of gastric acid secretion.     

Effect of antral instillation of bile salts on fasting serum gastrin levels

There have been several reports that bile salts instilled into a dog's alkalinized antral pouch cause acid secretion in a denervated fundic pouch. Antral gastrin release was assumed, but serum gastrin levels were not measured. In a randomized crossover study, serum gastrin levels were measured by radioimmunoassay during the infusion of a solution of bile salts (5 mM, pH 5.5, 280 mOsm, 37° C), or an identical saline solution without bile salts, into the pH-controlled (5.5), antrum of 8 volunteers. The mean baseline serum gastrin level (±se) was 18.7±1.0 and 20.5±0.9 pg/ml for the bile salt and control periods, respectively (NS). The serum gastrin rose promptly after bile salt infusion, but not after saline. The mean (±se) integrated gastrin response was 81±17 pg · min/ml during the bile salt infusions, but essentially zero (–3.3±22 pg · min/ml) during control infusions (P<0.02). The 40% rise in serum gastrin in the initial 15-min bile salt period was higher than in the control period (P=0.016). Thus we have shown, for the first time an increase in serum gastrin during the antral instillation of bile salts in man. The potential physiologic and/or patholgic importance of this finding has not been established.Dr. Levine was the recipient of National Health Service Award 5 F32 AM 05543-02.This paper was presented in part at the Annual Meeting of the American Gastroenterological Association in Las Vegas, Nevada, 1978.     

Changes in the intragastric distribution of Helicobacter pylori during treatment with omeprazole.

Omeprazole is a powerful inhibitor of gastric acid and may suppress Helicobacter pylori by effecting the pKa of H pylori urease, by altering the pattern of infection, or by promoting overgrowth of other bacteria. At routine endoscopy H pylori was detected by histology and culture before and after four weeks' treatment with omeprazole, 40 mg each morning. A 13C-urea breath test was also done at t = 0, 2, 4, and 6 weeks. Thirty nine patients with duodenal ulcer (n = 25) or reflux oesophagitis (n = 14) were studied, of whom 29 of 39 had H pylori infection. During omeprazole treatment, 13C-urea breath test values fell significantly--mean (SEM) values before treatment and at four weeks were 23.0 (2.1) and 15.5 (2.7) per mil respectively, p < 0.001. Before treatment H pylori was seen in 28 of 29 antral, 29 of 29 corpus, and 28 of 29 fundic biopsy specimens. After four weeks of omeprazole treatment, the histological density of H pylori in the antrum and corpus was reduced (p < 0.001), while that in the fundus was increased. The migration of H pylori from the antrum to the fundus was associated with a corresponding decrease in the activity of antral gastritis. H pylori was not seen in antral biopsy specimens from 12 of 29 patients whose median excess delta 13CO2 excretion fell from 23.0 to 9.9 per mil. In the body mucosa, 26 of 29 specimens were still positive for H pylori and there was no significant change in the gastritis type. Two weeks after finishing treatment, the mean (SEM) excess delta 13CO2 excretion returned to levels before treatment. Omeprazole decreases antral H pylori colonisation but increases that in the fundus. The changes in the intragastric distribution of the organism are associated with concomitant changes in the activity of gastritis and are matched by a progressive fall in the excretion of delta 13CO2.     

Prostaglandin E1 Inhibition of Acid but Not Gastrin

Prostaglandin E₁, while inhibiting gastric fistula and Heidenhain pouch acid output in the dog. did not inhibit gastrin released by acetylcholine irrigation of an isolated antral pouch independent of pH effect. Some increase in gastrin was noted to PGE₁ against u background of calcium infusion and following a meal. This increase is presumably due to acid inhibition and to an increase in intraluminal pH.     

Helicobacter pylori and luminal gastric pH

The relationships between gastric pH and Helicobacter pylori infection were studied in 37 consecutive subjects affected with nonulcer dyspepsia. Each underwent esophagogastroduodenoscopy with multiple gastric biopsies for both H. pylori and histologic assessment, and 24-hr antral pH monitoring. H. pylori was harbored by 59.5% of the subjects with whole gastric spread of infection in all but one patient. Histologic gastritis was shown in 70.3% of the subjects. H. pylori was strongly associated with gastritis, both antral nonatrophic and multifocal atrophic. The ranges of 24-hr pH values were 1.3-6.9 in the H. pylori-positive and 1.2-6.8 in the H. pylori-negative group. Differences in pH values between the two groups were not significant. Moreover, the mean percent time duration of pH above 2, 4, and 6 did not significantly differ between the two groups. Therefore, this study has shown that chronic H. pylori infection is not related to luminal gastric pH.     

Endogenous hypergastrinemia and cell proliferation in the fundic mucosa in dogs

Endogenous hypergastrinemia (P<0.01) was produced in 4 dogs with a Heidenhain pouch through surgical exclusion of the pyloric antrum. This was followed by acid hypersecretion and increased DNA synthesis and mitotic activity (P<0.01) in the mucosa of the Heidenhain pouch. The acid hypersecretion induced by histamine in beeswax in 4 other dogs did not increase the proliferative parameters in the pouch mucosa of the latter. A positive correlation (r=0.84,P<0.01) was found between the serum gastrin levels and the DNA synthesis index values measured in the 4 animals before antral exclusion, after antral exclusion, and after antrectomy. These data support the hypothesis that the trophic effect of gastrin on the fundic mucosa can be elicited by physiological doses of endogenous hormone.     

Pancreatic secretion stimulated by the action of alcohol on the gastric antrum

Summary Perfusion of an antral pouch with ethanol increased the pancreatic volume and enzyme content after a 10–30 min. latent period. Gastric secretion also increased in each experiment, but after a 30–40 min. latent period.Supported in part by a grant from the Licensed Beverage Industries.The authors wish to acknowledge the technical assistance of J. M. Eisenberg, B.S.     

Mechanical activity of muscular "patch pouches" from cat and rabbit stomachs

With a newly developed preparation (the gastric patch pouch), we compared the mechanical response of the proximal with that of the distal stomach to volume loads, drugs, and stimulation by an electrical field. Squares, 2 X 2 cm, were cut from the anterior and posterior walls of stomachs from cats and rabbits; the corresponding edges of opposing squares were sewn together. A luminal balloon served to change pouch volume and to monitor pouch pressure. Filling increased the width more than the length of most pouches; this difference was particularly marked in pouches from the rabbit fundus. Filling led to an initial pressure peak, after which pressure declined to a new baseline pressure plateau; emptying led to an initial pressure nadir, pressure recovery, and baseline pressure plateau. The difference between initial pressure and plateau pressure was larger in proximal than in distal pouches: hence, baseline pressures rose more sharply on filling and declined more steeply on emptying of antral than of proximal pouches. Pressure waves occurred in all antral pouches of cats and in some antral pouches of rabbits. Carbachol enhanced the pressure waves and isoproterenol inhibited them. In the fundic pouches, these drugs altered primarily the baseline pressure. Electrical field stimulation caused a relaxation in fundic pouches and a suppression of rhythmic contractions in antral pouches. The onset and the duration of nervous inhibition was comparable in fundic and in antral pouches. The baseline pressure of pouches was not affected by the presence or by the absence of the mucosa. This novel preparation is suitable to demonstrate differences in the volume-pressure relationships of the muscle coat of the proximal and the distal stomach.     

Motor responses to serotonin in isolated guinea pig fundus and antrum

The effects of serotonin on gut motility have been both excitatory and inhibitory. The purpose of the present study was to elucidate how serotonin influences motor activity in two functionally different parts of the stomach. Pressure recordings were made from fundic and antral pouches of isolated guinea pig whole stomach preparations. In the fundus serotonin induced relaxation, which developed gradually within 3 min. In the antrum serotonin initiated phasic contractions, which culminated within 3 min and then returned to near or below prestimulatory values. Whereas tetrodotoxin did not significantly reduce the fundic relaxation, the antral excitation was strongly inhibited by both atropine and tetrodotoxin, indicating different effect mechanisms in fundus and antrum.     

Nocturnal Antral pH Rises Are Related to Duodenal Phase III Retroperistalsis

The mechanisms behind nocturnal rises of gastricpH are unknown. We have analyzed the relation betweeninterdigestive duodenal peristalsis and nocturnal pH inthe gastric antrum. Simultaneous recording of antroduodenal pressures and intragastric pHwas performed in 11 healthy subjects (six men, fivewomen) overnight for 8 hr, using a catheter with sevenpressure recording points and an antral glass pH electrode. Three pressure recording sites wereclosely spaced in the descending duodenum. Altogether 46phase III activities were recorded. A retroperistalticsequence in the last part of phase III was observed in 31 phase III activities (67.4%),while 15 phase III activities lacked retroperistalsis.All subjects had retroperistalsis in at least one phaseIII at night with a median of 60% (52-100%) (interquartile range). The duration of thewhole phase III was 5.1 (3.1-7.0) min, whereas theduration of the retroperistaltic period was 2.0(1.5-3.2) min, corresponding to 45% (23-64%) of theduration of phase III. The peak of antral pH occurred7.4 (6.0-13.0) min from the start of the phase III inthe duodenum and and the rise in pH lasted for 8.0(4.8-12.0) min. Measurement of pH for a period of 10 min before and after phase III, demonstrated anincrease in median pH from 1.2 (1.1-1.9) to 3.2(1.6-4.7), respectively (P < 0.001). Phase IIIactivities without duodenal retroperistalsis were notfollowed by a significant antral pH change (median 1.7vs 1.8 before and after phase III, respectively).Increases of pH unrelated to phase III were uncommon,only 1.0 (1.0-2.2) events per night were observed and lasted for a short period of time, 2.1(0.5-3.2) min. The results indicate that the cyclic risein antral pH at night is due to a physiologicalduodenogastric reflux, caused by duodenalretroperistalsis in phase III. This reflux may play a role inprotection of the antral mucosa.     

Effect of the acid secretory state on intramural pH of rabbit gastric mucosa.

Intramural pH of the gastric mucosa was measured using a microelectrode technique in rabbit gastric pouches under different secretory conditions and luminal acidity. Exposure of spontaneously secreting or metiamide-treated fundic pouches to a relatively high concentration of luminal acid. HCl 120 mM, for 60 min, led to a marked net loss of luminal H+ which was associated with a significant decrease in the intramural pH (7.28 +/- 0.09 to 6.88 +/- 0.10 and 7.23 +/- 0.07 to 6.99 +/- 0.09, respectively). A linear relationship was observed between the rates of net disappearance of luminal acid and the intramural pH. All 10 spontaneously secreting and five metiamide-treated pouches had superficial mucosal erosions. In contrast, when fundic pouches were exposed to luminal acid in histamine-treated animals, the net loss of luminal H+ was negligible and the intramural pH remained at its base-line level (7.25 +/- 0.07). Histamine stimulation without acid in the lumen caused a small but insignificant increase in the intramural pH (7.27 +/- 0.03 to 7.39 +/- 0.05). Only three of the eight histamine-treated fundic pouches had lesions. In the antral pouches the intramural pH changes in response to exposure to luminal acid were smaller and histamine treatment did not influence the intramural pH. None of the antral pouches had lesions. The results suggest that acidification of the tissue by the diffusion of luminal acid may be an important factor in the pathogenesis of acute gastric ulceration. The acid secretory state of the gastric mucosa can significantly influence the acid-base balance in the mucosa and thus modify its response to acid diffusing from the lumen. Histamine stimulation protected the gastric mucosa by improving its buffering capacity and/or otherwise decreasing the diffusion of H+ from the lumen into the mucosa.