SUMMARY The effect of intraduodenal acid on pentagastrin-stimulated gastric secretion has been investigated in 12 normal subjects and 23 patients with chronic duodenal ulceration. Plasma secretin levels were monitored during each test using a highly sensitive radioimmunoassay.Significant inhibition of gastric secretion occurred in the normal subjects and duodenal ulcer patients. A significant rise in plasma secretin was observed in both groups after intraduodenal acid though there was a complete lack of correlation between the magnitude of the secretin response and the degree of gastric inhibition. Ten subjects received intraduodenal acid and a subsequent intravenous infusion of exogenous secretin (0.125-0.25 units/kg over six minutes). Gastric inhibition occurred after the acid instillation but not after secretin infusion despite plasma secretin levels greatly in excess of those produced by intraduodenal acid.These results suggest that release of secretin by itself cannot explain the gastric inhibitory response to intraduodenal acid in man.The presence of acid in the duodenum is known to inhibit gastric secretion both in animals (Pincus, Friedman, Thomas, and Rehfuss, 1944;Sircus, 1958) and in man (Shay, Gershon-Cohen, and Fels, 1942;Johnston and Duthie, 1964). The mechanism of this response is, however, uncertain. The main possibilities (which may of course interact) appear to be either a vagal reflex or a humoral response particularly involving secretin. The evidence for each of these views is fully discussed elsewhere (Ward, 1974). The role of the vagus has been examined in detail and it appears likely that gastric inhibition is dependent on a vagal reflex in man (Ward, 1974). Strong claims, however, have been made that in dogs secretin is the mediator of gastric inhibition by intraduodenal acid (Johnson and Grossman, 1968) and the present study was therefore undertaken to examine the response with particular emphasis on the role of secretin. Materials and MethodsThe response to intraduodenal acid was investigated in 35 patients, 10 of whom also received an intravenous secretin infusion. There were 12 normal subjects (Orm, 2f) and 23 patients (21m, 2f) with chronic duodenal ulceration. The average age of Received for publication 10 July 1974. the normal subjects was 38 years (range 21-63) and their average weight 71 kg (range 55-83 kg). These subjects were awaiting minor inpatient surgery and all were free of gastrointestinal symptoms. The duodenal ulcer patients were awaiting gastric surgery and in all cases the pathology was confirmed subsequently at laparotomy. Their average age was 42 years (range 27-67) and their average weight 68 kg (range 52-82 kg).A duodenal inhibitory test (Ward, 1973) was carried out on each of the normal subjects and duodenal ulcer patients. The gastric stimulus was an intravenous infusion of pentagastrin at a dose rate of 6 ,g/kg/hr. Gastric samples were collected at 10-minute intervals throughout the test.Once a secretory plateau had been reached 40 ml of 0O1N hydrochloric acid ...

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SUMMARY Gastric secretion in man is inhibited by the presence in the duodenum of hyperosmolar and hypoosmolar solutions. Both acid and pepsin outputs are affected. There is no change in hydrogen, sodium, or potassium ion concentration in the gastric juice. Pepsin concentration, however, is reduced by all inhibitory stimuli. Inhibition is thought to act directly upon parietal and chief cells, and a possible basis for this mechanism is discussed. The response is similar in control subjects and duodenal ulcer patients; there is in particular no evidence of impaired inhibition in the ulcer group. An anomalous feature is the relatively small inhibition of acid output after hypertonic saline in control subjects compared with the duodenal ulcer patients.

Acid in the duodenum is known to inhibit gastric secretion in man but whether this response is a humoral or a vagal phenomenon is unknown. If a vagal reflex is involved then selective and highly selective vagotomy, by preserving the duodenal nerve supply, could ofler advantages over truncal division. This study was designed to investigate this claim. The efect of intraduodenal hydrochloric acid on pentagnstrin-stimulated gastric secretion was srudied in 17 control subjects, 32 preoperative duodenal ulcer patients and 28 vagotomized patients (16 truncal vagotomy and pyloroplasty; 6 selective vagotomy and pyloroplasty; 6 highly selective vagotomy). Inhibition of acid output occurred in 15 control subjects, and the mean inhibition for the group was 268+ 0.39 mEqllO minures ( P < 0.001). Inhibition occurred in 22 duodenal ulcer patients, and the mean reduction in acid output for the entire group was 2,26 ? 0.46 mEqll0 minutes ( P < 0.001). Intraduodenal acid failed to produce a response in the vagotomized patients irrespective of the presence or absence of a duodenal nerve supply.These results suggest that gastric secretory inhibition by intraduodenal acid is a vagal phenomenon in man; selective and highly selective vagotomy do not appear to carry any particular advantage over truncal section in terms of preserving this response.

SUMMARY The release of secretin by intraduodenal acid has been measured by means of a highly sensitive radioimmunoassay in 12 normal subjects, 23 duodenal ulcer patients, and 14 vagotomized patients (6 TV + P; 4 SV + P; 4 HSV). A highly significant response occurred in all three groups. There was no significant difference between the groups either in the magnitude or timing of this response, though the absolute values for pre-stimulation and peak secretin were significantly smaller in preoperative duodenal ulcer patients than in either the normal subjects or the vagotomized patients. The secretin response was similar after truncal, selective, and highly selective vagotomy. These results suggest that secretin release is not dependent on intact vagal innervation of the small intestine in man.Vagal influences are known to be important in the release of gastrin (Grossman, 1967), but whether the vagus is involved in secretin release has not been established. The secretin response to duodenal acid has recently been measured in man using a radioimmunoassay (Ward and Bloom, 1974) and in the present study this work has been extended to include an assessment of the post vagotomy response. Methods SUBJECTSTwelve normal subjects (10 males; two females), 23 duodenal ulcer patients (21 males; two females), and 14 vagotomized patients (12 males; two females) were investigated. The mean ages in the three groups were 38 years (21-63 years), 42 years (27-67 years), and 45 years (30-66 years). The mean weights were 71 kg (55-83 kg), 68 kg (52-82 kg), and 68 kg (48-79 kg) respectively. In the vagotomized group, tests were undertaken six months or more after truncal vagotomy and pyloroplasty (six), selective vagotomy and pyloroplasty (four), and highly selective vagotomy (four). All the patients were insulin negative at the time of testing according to Hollander's original criteria (Hollander, 1948), as well as the criteria of subsequent authors (Waddell, 1957;Bachrach, 1962;Ross and Kay, 1964;Bank et al., 1967).Intraduodenal acid may inhibit gastric secretion in addition to provoking secretin release (Johnston and Duthie, 1964) and the present results were Received for publication 10 October 1975. obtained during tests in which both phenomena were studied. Details regarding the changes in acid output are described more fully elsewhere (Ward, 1974).Gastric secretion was stimulated by a continuous intravenous infusion of pentagastrin (6 ,tg/kg/hour in normal subjects and preoperative ulcer patients, 9 ,ug/kg/hour in vagotomized patients) and 10 minute gastric collections were made throughout each test. Once a secretory plateau had been reached, which was usually by an hour, 40 ml 0.1 N hydrochloric acid, at 37°C, were infused into the distal duodenum over a five minute period. Gastric collection was then continued for a further hour. Secretin levels were monitored at intervals throughout each test. Blood was withdrawn from an antecubital vein into heparin-trasylol, then rapidly centrifuged and deep frozen. Samples were taken at 10...