Gastric acid response to antrum distension in man.

Gastric acid secretion under basal conditions and in response to graded balloon distension (50 ml, 100 ml, 150 ml) of the antrum was determined in healthy subjects and in peptic ulcer patients. In patients with a quiescent duodenal ulcer or a gastric ulcer antrum distension produced slight acid responses. The acid response to antrum distension was of quantitative importance only in patients with an active duodenal ulcer, amounting to 35 percent of the maximal acid response to pentagastrin. The healthy subjects did not respond with acid secretion to antrum distension. The pH of the gastric contents in the present series was 1.8-3.0, being lowest in patients with an active duodenal ulcer. Thus, the acid secretory effect of mechanical stimulation of the antrum seems qualitatively different in healthy subjects and ulcer patients, with a marked acid response in patients with an active duodenal ulcer.

The effect of long-term postoperative pentagastrin infusion on the maximal acid responses to pentagastrin in patients subjected to antrectomy.

Six duodenal ulcer patients subjected to antrectomy were given a continuous i.v. infusion of pentagastrin in a dose just below ED50 during 1 week in the immediate postoperative course. The peak acid output following stimulation with pentagastrin (PAOG) was determined preoperatively and 1 and 5 weeks postoperatively. PAOG was determined preoperatively and 1 week after antrectomy in a control group of 25 duodenal ulcer patients, and preoperatively and 5 weeks after antrectomy in another control group of 19 duodenal ulcer patients. One week post-antrectomy the PAOG was significantly less reduced (23%) in the pentagastrin infusion group than in the control group (46%). The reductions of PAOG 5 weeks post-antrectomy were not significantly different in the pentagastrin infusion group and the control group. The results show that the dysfunction of the parietal cells, reflected in a decreased capacity to secrete acid following antrectomy, can be partly reversed by continuous administration of pentagastrin in the immediate postoperative course. The results are interpreted as suggesting that antral gastrin in man, besides its property to stimulate acid secretion, also has a trophic effect on the parietal cells in analogy with the postulated trophic effect of antral gastrin in rats.

Effects of fundic distention on pentagastrin-stimulated gastric acid secretion in man.

The acid secretory effect of combined stimulation with balloon distention of the fundus and body of the stomach and intravenous infusion of pentagastrin has been studied in patients with duodenal ulcer (DU) and in healthy subjects. In 8 nonoperated DU subjects and in 5 DU patients subjected to proximal gastric vagotomy, low grade fundic distention moderately enhanced the acid output evoked by a threshold dose of pentagastrin. Fundic distention with a baloon volume eliciting a maximal acid response to distention either left unchanged or suppressed the maximal acid secretory rate produced by pentagastrin in 7 nonoperated and 6 vagotomized DU patients and in 5 healthy subjects. The heterogeneous secretory effects of maximal stimulus combination suggest that fundic distention has a complex action on acid secretion eliciting a hitherto unknown inhibitory effect as well as a cholinergic activation of the parietal cell area. This complex action may explain the failure of fundic distention to augment markedly the action of pentagastrin in the present study.

Effect of atropine and proximal gastric vagotomy on the acid response to fundic distension in man.

In four healthy subjects and in 12 patients with duodenal ulcer (DU), graded balloon distension of the gastric fundus and body caused increments in acid output related to the distension volumes. The mean peak distension response amounted to about 50% of the mean peak acid output (PAOpg) evoked by intravenous infusion of pentagastrin in a dose of 300 microng/h, eliciting maximum observed secretory response. During distension with the largest balloon volume, 1-0 mg atropine injected intravenously significantly depressed the acid secretory rate, the median inhibition amounting to about 80%. In two patients with DU, 2-5 mg atropine completely abolished acid secretion during fundic distension. In nine subjects with DU, complete proximal gastric vagotomy profoundly depressed the secretory responses to graded fundic distension, eliminating the acid response to the smallest balloon volume used. A slight, but significant, response to the largest distension volume persisted after complete vagotomy. Incomplete proxomal gastric vagotomy was found to reduce only moderately the distension responses in five patients, and the peak acid response to fundic distension as related to PAOpg remained unchanged. In conclusion, distension of the gastric fundus and body in man stimulates acid secretion by means of an atropine-sensitive, presumably cholinergic, reflex mechanism and the findings after vagotomy are in agreement with the concept that this reflex mechanism is conveyed by both short intramural and long vagovagal pathways.

The effect of antral distension on acid secretion and plasma gastrin in duodenal ulcer patients.

The effect of antral balloon distension on acid secretion and the plasma gastrin concentration was studied in 8 duodenal ulcer patients. Antral distension significantly increased the acid secretion to about 30% of the peak acid response to pentagastrin without any change in the plasma gastrin concentration. Antral distension and concomitant intragastric neutralization, with the intention of facilitating release of antral gastrin, produced about the same acid response and did not evoke any plasma gastrin increment. The results suggest that the acid response to antral distension in duodenal ulcer patients is evoked without contribution of the gastrin mechanism, and that the acid response is probably mediated via a pyloro-oxyntic reflex. In this respect the duodenal ulcer patient seems to differ from the healthy subject, in whom antral distension produces no acid response, and from the dog, in which release of gastrin as well as pyloro-oxyntic reflex participate in the acid response to antral distension.

Effect of fundic distension on gastric acid secretion in man.

The effect of distension of the fundus and body of the stomach on gastric acid secretion was studied in 26 patients with duodenal ulcer and six healthy subjects. Graded distension produced by inflating a rubber balloon to volumes of 150, 300, and 600 ml resulted in significant sequential increments of acid output. The secretory response outlasted stimulation by at least one hour. In both groups of subjects, the highest acid output obtainable with fundic distension amounted to just above 50% of the maximum secretory response evoked by intravenous infusion of pentagastrin. A significant correlation was found between the peak secretory rates observed during fundic distension and after pentagastrin stimulation. It is concluded that distension of the oxyntic gland area in man is a potent stimulus for gastric secretion of acid and that patients with duodenal ulcer are no more sensitive to this stimulus than healthy subjects.

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.

Evidence for a defective inhibition of pentagastrin-stimulated gastric acid secretion by antral distension in the duodenal ulcer patient.

Graded antrum distension by 50-, 100-, and 150-ml balloon volumes significantly stimulated gastric acid secretion in 6 duodenal ulcer patients, but had no stimulatory effect in 6 healthy subjects. Antrum distension by 150-ml balloon volume had no effect on the acid response to submaximal stimulation by a continuous intravenous infusion of pentagastrin in the duodenal ulcer patients, but significantly inhibited this response in the healthy subjects. The inhibition by antrum distension in the healthy subjects amounted to 20%. The results suggest that antrum distension elicits stimulatory as well as inhibitory mechanisms in man with inhibition of acid secretion predominating in healthy subjects and stimulation of acid secretion predominating in duodenal ulcer patients. The mechanism of inhibition is unknown.

Gastric acid responses to graded i.v. infusion of pentagastrin and histalog in peptic ulcer patients before and after antrum-bulb resection.

Gastric acid responses to graded i.v. infusion of pentagastrin and Histalog were determined in peptic ulcer patients. Single-day multiple-dose tests were performed. The sensitivity to the humoral stimuli as determined by the calculated ED50's was not significantly different for duodenal ulcer patients with moderate (DUmod) or massive (DUmass) observed hypersecretion or for gastric ulcer (GU) patients: median ED50's of pentagastrin were 6.2, 6.6, and 13.1 mug/h in 18 DUmod, 22 DUmass and 7 GU patients respectively, and median ED50's of Histalog were 16.6, 25.3, and 17.1 mg/h in 14 DUmod, 10 DUmass and 6 GU patients respectively. Antrum-bulb resection significantly reduced basal acid secretion and maximal acid responses to the humoral stimuli (about 45% reduction) but did not significantly change the loss of gastric contents to the intestine or the sensitivity to the humoral stimuli (median ED50 of pentagastrin increased from 5.2 to 6.7 mug/h in 14 patients, and median ED50 of Histalog increased from 16.0 to 20.8 mg/h in 12 patients), suggesting that the intact antrum-bulb region of the ulcer patient is controlling the capacity to secrete acid, and indicating that antrum-bulb gastrin is an important trophic factor for the parietal cells in man.

Treatment of acute massive gastroduodenal haemorrhage with cimetidine in elderly patients.

Ninety-two patients over the age of 60 with acute upper GI-haemorrhage were included in a prospective randomized doubleblind three-centre study of the effect of a five day treatment with cimetidine. Twenty patients had to be excluded because of different reasons. The remaining 72 patients bled from either erosive gastritis, gastric ulcer or duodenal ulcer. Thirty-two patients received cimetidine and 39 placebo. There was no difference in the number of transfusions, rebleedings or operative interventions. Mortality was 1/33 (3%) in the cimetidine group compared to 5/39 (13%) in the placebo group (NS). In the gastric ulcer group there was no mortality among 10 cimetidine patients compared to a mortality of 4 of 12 (33%) patients receiving placebo (p less than 0.05). It is concluded with caution that cimetidine might be effective in haemorrhage from gastric ulcer in patients 60 years and older. For convincing conclusions a larger study of patients with bleeding ulcers is desirable.