Gastric acid and pancreatic polypeptide responses to modified sham feeding: indication of an increased basal vagal tone in a subgroup of duodenal ulcer patients.

The effect of sham feeding upon gastric acid secretion and pancreatic polypeptide release was investigated in 28 patients with duodenal ulcer in order to evaluate whether high basal vagal activity is the cause of basal acid hypersecretion in patients with duodenal ulcer and basal secretion higher than 30% of their peak acid output. The patients were divided into two groups based on the ratio of basal/pentagastrin stimulated peak acid output (BAO/PAO) was higher or lower than 0.30: group A n = 19 (BAO/PAO less than or equal to 0.30) and group B n = 9 (BAO/PAO greater than 0.30). Gastric acid response to sham feeding (SAO) was significantly higher than basal level in group A (SAO: 11.4 mEq/h (2.5-20.1) vs BAO: 5.2 mEq/h (0.8-22.9), p less than 0.01, median (range)) while in group B the acid secretion did not increase with sham feeding (SAO: 9.6 mEq/h (4.5-13.6) vs BAO: 8.8 mEq/h (6.3-13.8) ns, median (range)). A negative correlation (r= -0.6118226, p less than 0.01) was found between acid increase expressed as basal subtracted sham feeding response (SAO-BAO) and BAO/PAO ratio of the entire group of duodenal ulcer patients (n = 28) suggesting that the greater is basal acid secretory capacity the smaller is acid increase in response to residual vagal activation. Pancreatic polypeptide response to sham feeding was higher in group A than in group B but no correlation (r = 0.20, n = 28) nor individual covariation was found between acid and pancreatic polypeptide secretions during vagal stimulation. sham feeding did not change serum gastrin. It is concluded that an increased vagal stimulation seems to be the cause of basal hypersecretion in a subgroup of patients with duodenal ulcer. The lact of correlation between the pancreatic polypeptide and acid responses to vagal stimulation interferes with the reliability of pancreatic polypeptide as indicator of vagal tone on gastric parietal cells.     

Effect of proximal gastric vagotomy and anticholinergics on the acid and gastrin responses to sham feeding in duodenal ulcer patients.

Plasma gastrin concentrations and gastric acid output after modified sham feeding were determined in 20 duodenal ulcer patients. Sham feeding produced an acid response corresponding to 40-68% of the maximal acid output after pentagastrin stimulation, with no significant increase of plasma gastrin concentrations. In eight patients proximal gastric vagotomy almost abolished the acid responses to both insulin hypoglycaemia and sham feeding. Sham feeding in the vagotomised patients did not change the gastrin concentrations in plasma. After pretreatment with benzilonium, an anticholinergic with minimal central nervous effects, plasma gastrin concentrations increased after sham feeding. The study confirms that sham feeding is a poor stimulus for gastrin release in duodenal ulcer patients and supports a cholinergic inhibition of gastrin release. Intravenous injection of benzilonium bromide in a dose close to 70 micrograms/kg, and atropine in the low dose of 30 micrograms/kg inhibited the acid response to sham feeding by about 65%. Atropine in a dose of 50 micrograms/kg virtually abolished the acid sham feeding response, possibly owing to ganglionic or central nervous blockade. Vagal activation of the acid secretory glands does not seem to involve a purely cholinergic neurotransmission.     

Modified sham feeding test after parietal cell vagotomy for juxtapyloric ulcer disease in patients with and without recurrent ulcers

The mean of individual coefficients of variation of acid output after modified sham feeding was 39% in 22 patients operated on with parietal cell vagotomy. The reproducibility of the interpretation of the sham feeding test as 'positive' or 'negative' was good. An intragastric infusion of a marker to correct for pyloric loss did not increase the accuracy of the test. The prognostic value of the qualitative estimation of the sham feeding test 2 months after operation to predict recurrent ulcer after parietal cell vagotomy was poor in 39 patients studied prospectively over 3 years. With the criterion sham feeding minus basal acid output over 1.0 mmol/30 min as a positive test, 63% of patients with a positive and 24% with a negative test later had recurrent ulcers. The consistency of the interpretation as either positive or negative was low in annual tests during the 3 years of follow-up study. After parietal cell vagotomy the sham-feeding-stimulated acid output was higher in patients with duodenal than in those with prepyloric recurrent ulcers and also in those without recurrences. This indicates that the amount of vagal innervation left after parietal cell vagotomy is of special importance in the occurrence of duodenal ulcer relapse.     

Effects of truncal vagotomy and antrectomy on bombesin-stimulated pancreatic secretion,release of gastrin,and pancreatic polypeptide in the anesthetized dog

The short-term effects of truncal vagotomy and antrectomy on bombesin-stimulated pancreatic secretion and release of gastrin and pancreatic polypeptide (PP) were studied in 18 anesthetized dogs. Together with an intravenous infusion of secretin (250 ng/kg/hr) bombesin (500 ng/kg/hr) was given before and after truncal vagotomy, antrectomy, and sham operation (N=6 dogs per group). Peak incremental pancreatic protein output in procedures (tachyphylaxis). Neither truncal vagotomy nor antrectomy significantly altered the pancreatic protein response to bombesin when compared with sham operation. Bombesin produced a mean 1-hr increase over basal of 196 pM for gastrin, which was abolished by antrectomy but not appreciably affected by truncal vagotomy and sham operation. The mean 1-hr increment (207 pM) for PP in response to bombesin was not changed by truncal vagotomy, antrectomy, and sham operation. This study shows in the anesthetized dog that exogenous bombesin stimulates release of PP as well as gastrin; that the release of gastrin by bombesin is not vagally dependent; that neither truncal vagotomy nor antrectomy alter the release of PP by bombesin; and that the action of bombesin on pancreatic protein secretion does not depend on release of gastrin or on intact vagal nerves.Parts of this paper have been presented at the 12th European Pancreatic Club Meeting, Copenhagen, Denmark, October 11–13, 1979, and at the 3rd International Symposium on Gastrointestinal Hormones, Cambridge, England, September 15–18, 1980.     

Gastric acid and pepsin secretion in response to modified sham feeding in active and inactive duodenal ulcer disease

Gastric secretion of acid and pepsin were studied under basal conditions, in response to modified sham feeding (MSF), and in response to pentagastrin in 15 male controls and in 11 and 10 male patients with active and inactive duodenal ulcer disease, respectively. In general, patients with ulcer disease produced more acid and pepsin than controls. No differences between the two ulcer groups were found for basal and pentagastrin-stimulated secretions. The response patterns to MSF, however, were different in the two groups. After an early peak, acid and pepsin responses rapidly decreased, approaching basal level in patients with active duodenal ulcer and in controls. In patients with inactive disease, however, the decrease was less marked, and in some patients the secretion continued to increase for 60 min. When expressed as fractions of the responses to pentagastrin, the acid and pepsin responses during the fourth 15-min period were significantly greater in patients with inactive duodenal ulcer disease than in patients with active disease and in controls. The findings indicate that the gastric response to vagal stimulation is different in patients with active and inactive duodenal ulcer disease.     

Effects of proximal gastric vagotomy on gastric secretory and plasma hormonal responses to sham feeding in patients with duodenal ulcers

The effects of proximal gastric vagotomy on the gastric secretion of acid and pepsin, and on the release of gastrin and pancreatic polypeptide in response to sham feeding were assessed comparatively within 1-4 months after surgery in 32 male duodenal ulcer patients. Each test comprised three successive periods: basal, modified sham feeding (MSF) and pentagastrin stimulation. In each test period the acid output was strongly correlated with the corresponding pepsin output, both parameters being reduced to similar extents after vagotomy. The percentage of postoperative reduction of MSF-induced acid and pepsin outputs was positively correlated with the preoperative values. MSF resulted in a limited but significant release of gastrin, the response being significantly greater after surgery. The MSF-induced release of pancreatic polypeptide was significantly reduced by proximal gastric vagotomy, the reduction percentage being negatively correlated with the time elapsed since surgery. Neither pre- nor post-operatively did the gastrin and pancreatic polypeptide responses bear any relationship to the other parameters tested. We conclude that the study of sham feeding responses of pepsin, gastrin and pancreatic polypeptide provides no further information than does the measurement of acid secretion for the segregation of duodenal ulcer patients, especially with respect to follow-ups for ulcer recurrence.     

Effects of partial truncal vagotomy on intragastric pressure responses to vagal stimulation and gastric distension in ferrets.

Changes in intragastric pressure after dorsal truncal vagotomy, investigated by stimulation of the surviving vagal branches and by step inflation of the stomach, were divided into an early phase lasting five days, and a late phase continuing for at least three months. During the early phase the amplitude of vagal evoked contraction was diminished but the resting pressure and the response to gastric inflation were increased. After the fifth day vagal evoked contractions doubled in amplitude but the resting pressure and the response to step inflation of the stomach returned to control levels. Ventral vagotomy did not produce any substantial changes. Alterations to gastric and body weight, or to the relation between resting pressure and evoked contraction and relaxation were excluded as causes of the enhanced vagal effectiveness. Sprouting of axons into denervated territory occurred too late to explain the changes, but an increase in synaptic density within the innervated territory has not been ruled out.     

Action of omeprazole (a benzimidazole derivative) on secretory responses to sham feeding and pentagastrin and upon serum gastrin and pancreatic polypeptide in duodenal ulcer patients.

The effects of omeprazole, a benzimidazole derivative, have been determined on the secretory responses to modified sham feeding and pentagastrin, and upon serum gastrin and pancreatic polypeptide concentrations in duodenal ulcer patients. Intragastric administration of omeprazole in doses of 2 and 6 mumol/kg produced, respectively, about 50% and 90% reduction in acid outputs in responses to modified sham feeding and pentagastrin without affecting serum gastrin and pancreatic polypeptide response to modified sham feeding.     

Gastric acid response to modified sham feeding in patients with duodenal ulcer: Is increased vagal tone the cause of basal acid hypersecretion?

In order to test the hypothesis that increased basal vagal tone causes basal acid hypersecretion in duodenal ulcer (DU), the effect of sham feeding on gastric acid secretion was studied in 26 patients with DU and 20 healthy controls. Basal acid output (BAO), sham feeding-stimulated acid output (SAO) and peak histamine-stimulated acid output (PAO) were significantly higher in DU patients compared with healthy controls (P less than 0.01). The BAO/PAO ratio in DU patients (0.28 +/- 0.03) was not significantly different from that of healthy subjects (0.19 +/- 0.03), indicating that the higher BAO in DU patients group, as a whole, was due to a higher parietal cell mass. The basal subtracted response to sham feeding expressed as a fraction of secretory capacity [(SAO-BAO)/PAO], which correlates inversely with the basal vagal tone, was not significantly different in the patients and control subjects (0.27 +/- 0.03 versus 0.3 +/- 0.03; P greater than 0.05). Based on the data from the healthy controls, a ratio of BAO/PAO greater than 0.44 was defined as abnormal (using 95% confidence limits) and it indicated marked basal acid hypersecretion. Four of 26 DU patients had basal acid hypersecretion (that is, BAO/PAO greater than 0.44), but only two of them did not show an increase over their basal rate of secretion in response to sham feeding. All other DU patients, including two with marked basal acid hypersecretion, and all healthy controls showed an appreciable increase in their acid secretion in response to sham feeding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of endogenous pancreatic glucagon on gastric acid secretion in patients with duodenal ulcer before and after parietal cell vagotomy.

The effect of endogenous pancreatic glucagon on submaximal pentagastrin stimulated gastric acid secretion was studied by infusion of 1-arginine in patients with duodenal ulcer before and after parietal cell vagotomy without drainage (PCV). Preoperatively infusion of 1-arginine resulted in a marked inhibition of acid secretion, whereas no effect was found postoperatively. Plasma glucagon concentrations were identical pre- and postoperatively, fasting as well as during arginine infusion. Serum gastrin concentration rose after PCV but not unaffected by arginine infusion both pre- and postoperatively. The study demonstrates that intact vagal innervation of the fundic glands is a condition of inhibition of pentagastrin induced acid secretion by pancreatic glucagon released by infusion of 1-arginine.     

Gastric acid secretion and risk of recurrence of duodenal ulcer within six to eight years after truncal vagotomy and drainage

The value of insulin and augmented histamine tests in predicting recurrence of duodenal ulcer within six to eight years after truncal vagotomy and drainage was assessed in a series of 500 consecutively and electively operated patients. Criteria of recurrence were established by a discriminative analysis of gastric acid secretion parameters. Recurrence was predicted with a probability of about 75% in patients with dyspepsia, the proportion between recurrences and dyspeptic nonrecurrences being 1:1. The discriminatory ability of the insulin test was no better than that of the postoperative histamine test. Men with a preoperative PAO > 46.1 m-equiv/h had a risk of recurrence of 21%, women with a PAO > 41.5 m-equiv/h, 28%. Below these levels the risk was 5 and 1% respectively, demonstrating that recurrence after vagotomy is related to the number of parietal cells before vagotomy. A rationale is provided for antrectomy and vagotomy in duodenal ulcer patients with a high number of parietal cells.     

The effect of parietal cell vagotomy and selective vagotomy with pyloroplasty on gastric acid secretion. A prospective randomized study.

The insulin- and pentagastrin-stimulated gastric acid secretion was studied before and 1 week, 1 month, 6 months and 1 year after parietal cell vagotomy (PCV) and selective vagotomy with pyloroplasty (SV + P) in 50 patients who took part in a consecutive randomized trial. The randomization and the operations were performed in such a way that the extent of the denervation of the proximal stomach was identical in the two groups. Basal acid output and the insulin-stimulated acid secretion were significantly increased from 1 month to 1 year after PCV, while there was no such increase after SV + P. There was no change of the pentagastrin-stimulated acid secretion (PAOP) from 6 to 12 months in either groups. One year postoperatively PAOP was significantly greater after PCV than after SV + P. The results are compatible with vagal reinnervation after PCV and support the assumption of a sprouting from the innervated gastric antrum.     

Modified sham feeding and Congo red test in determining completeness of vagotomy

Gastric acid response to modified sham feeding was evaluated in 14 patients with duodenal ulcer prior to vagotomy and in 18 patients after vagotomy. Nine patients in the latter group had recurrent ulcer, suggesting inadequate vagotomy. Based on values in the 32 tests (14 pre and 18 postoperative), cut-off levels of six secretory indices were selected to provide a specificity of 1.00 for the presence of ulcer. When applied separately to the 18 postoperative patients and to the 13 patients who underwent the endoscopic congo red test, observed volume of 75 ml/h and peak volume of 90 ml/h following sham feeding gave specificity, sensitivity and efficiency of 1.00 each in determining inadequate vagotomy. The endoscopic congo red test done in 13 post-vagotomy cases showed a sensitivity of 1.00, and high specificity (0.89) and efficiency (0.92). Measurement of crude gastric juice response to modified sham feeding is a convenient bedside test to confirm inadequate vagotomy. The endoscopic congo red test is also useful, especially as a screening test, and has the added advantage that it can be used intra-operatively.     

Effects of modified sham feeding on ghrelin levels in healthy human subjects

The mechanisms involved in the preprandial rise and postprandial fall of circulating ghrelin levels are as yet unknown. Many hormonal and metabolic responses to nutrient intake begin during the cephalic or preabsorptive phase and are mostly mediated by the autonomous nervous system. The aim of the present study was to investigate the effects of the cephalic phase on ghrelin response to feeding in human subjects. The modified sham feeding (MSF), a well established technique in which nutrients are smelled, chewed, and tasted, but not swallowed, was used. Sixteen healthy volunteers (seven men and nine women; mean age +/- sd: 31 +/- 8 yr; body mass index, 22 +/- 3 kg/m(2)) were studied after overnight fasting. Seven of them received a standardized mixed meal, and nine underwent MSF. Blood samples for ghrelin, insulin, and glucose were taken at time -30, 0, 15, 30, 45, 60, 120 min during both tests. Pancreatic polypeptide determinations were evaluated at all times as markers of vagal activity only during MSF. Ghrelin levels significantly increased from time -30 to 0 min before the two tests, then significantly decreased: after the real feeding from 933 +/- 479 pg/ml (277 +/- 142 pmol/liter) to 455 +/- 185 pg/ml (135 +/- 55 pmol/liter; P < 0.05), and after the sham feeding from 917 +/- 313 pg/ml (272 +/- 93 pmol/liter) to 519 +/- 261 pg/ml (154 +/- 77 pmol/liter; P < 0.05). There were no significant differences between the patterns of the responses as evaluated by ANOVA (P = 0.863). As expected after MSF, plasma pancreatic polypeptide concentrations promptly increased from 58 +/- 29 pg/ml (14 +/- 7 pmol/liter) to 113 +/- 38 pg/ml (27 +/- 9 pmol/liter) at 15 min (P < 0.01). Both insulin and glucose levels increased during the actual mixed meal, whereas they were not significantly modified by MSF. In conclusion, circulating ghrelin concentrations are decreased by sham feeding as they are by real feeding in humans. These findings underline the importance of the cephalic response to nutrient intake, i.e. the role of vagal activity, in the control of ghrelin secretion.