Fasted, anesthetized female rats were used to test the effects of sucralfate (Sc) on the response of the gastric mucosa to ethanol (EtOH) in NaCl or taurocholic acid (TcA) in HCl. The trachea was cannulated and the esophagus and pylorus were ligated. Tubes placed into the stomach permitted instillation of test solutions and determinations of transmucosal potential difference (PD). All periods were 15 min. Each test began with a baseline 150 mM HCl period followed by two treatment periods; in the first, 5600 mg Sc in NaCl or NaCl alone was placed in the stomach; in the second, neutral EtOH or acidified TcA solution was added. In the final two posttreatment test periods, the pH of the gastric contents of the animals treated with Sc was higher, the disappearance of H+ was less, and the index of mucosal damage was reduced. The results demonstrate that Sc has a protective effect on the gastric mucosa of rats. Pretreatment with Sc also reduced the net Cl-loss from the contents and produced an unexplained significant reduction in PD. Sc formed a white coating over the glandular mucosa. This coating may a play a role in its protective action.

Because four successive weekly exposures of the gastric mucosa of intact dogs to bile did not alter the appearance or the barrier function of the mucosa during subsequent challenges with bile, the effects of chronic continuous exposure to bile were tested. This was accomplished by diversion of the flow of bile from the duodenum into the stomach by cholecystogastrostomy and diversion of the common bile duct. After four weeks, on endoscopic examination the mucosa was dark red but covered in some areas by a creamy coloured, strongly adherent pseudomembrane. Histologically the mucosa was normal. Ion fluxes, when an acid test solution was used, were close to normal. Differences between control dogs and those with chronic bile diversion became very evident, however, when the mucosa was exposed to increasing concentrations of bile. The control dogs displayed increases in net fluxes of H+, Na+, Cl- and K+ as the concentration of the bile was increased but the dogs with chronic bile diversion did not. Also the changes in PD and fluxes in K+ were less in the dogs with bile diversion. In the intact control dogs bile placed in the stomach always produced bleeding and hemorrhagic erosion; in the dogs with chronic bile diversion added bile in the stomach never caused bleeding and the mucosa appeared normal on endoscopic and histological examination. We conclude that the resistance of the gastric mucosa to the barrier breaking action of bile was increased in the dogs with chronic gastric bile diversion.

Experiment 1 demonstrated that gastric mucosal damage in rats induced by lateral hypothalamic (LH) lesions could be significantly reduced by antisecretory doses of propantheline, cimetidine, and by vagotomy, however, only propantheline also prevented hypersalivation and chromodacryorrhea. These results indicate that a primary effect of LH lesions is to produce an abrupt increase in parasym-pathetic activity. Experiment 2 showed that gastric mucosal barrier functions were altered by LH lesions even before visible defects of the mucosa were present. It is suggested that an increase in permeability of the gastric mucosa may play an important role in the pathogenesis of gastric ulceration induced by hypothalamic damage.

Interest in the prostaglandins as possible gastric-mucosal cytoprotective agents was first aroused by the oberved antagonism between these compounds and ulcerogenic anti-inflammatory drugs. It has now been shown that several PGs can depress gastric acid secretion and reduce HCl-induced lesions in experimental animals. The clinical implications appear to be well worth exploration.

In dogs with electrodes chronically implanted on the stomach and duodenum, graded doses of intravenously infused synthetic human unsulfated little gastrin (G17-I) produced, in both the stomach and duodenum, graded increases in a) frequency of pacesetter potential, and b) incidence of pacesetter potentials with action potentials. The threshold doses of gastrin for these effects were about 25 pmol kg-1 h-1 in the stomach and about 50 pmol kg-1 h-1 in the duodenum. These doses of gastrin are similar to the threshold dose for gastric acid secretion.

The effects of two exposures of the gastric mucosa to either 10 mM taurocholic acid (TcA) or 20% ethanol, both in 150 mM HCl, on transmucosal potential difference (PD) and net fluxes of H+, Na+, and K+ ions have been tested in the rat. The interval between exposures was 30 min. The results demonstrated that the first exposure of the gastric mucosa, either to TcA or to ethanol, reduced the net fluxes of H+, Na+, K+ and the change in transmucosal PD induced by the second exposure, indicating an increased resistance of the mucosa to the barrier breaking effects of TcA or ethanol.

1. Szurszewski (1969) described a cyclic recurring, caudally migrating band of intense action potential activity, the activity fromt, in the small bowel of dogs fasted 18–21 hr. The finding has been confirmed by Carlson, Bedi & Code (1972) and by Grivel & Ruckebusch (1972). The objectives of the present study were to extend these observations first by indentifying the full sequence of myo‐electric events in the stomach and small bowel of healthy conscious dogs fasted for 24–48 hr and for longer periods and second by determining the effect of ingestion of mild and of saline solution on the complex and the role of gastric distension in their action. 2. Under surgical anaesthesia, silver‐silver chloride electrodes were implanted on the serosal surface of the stomach and small bowel of seven dogs, and recordings of electric activity were started when the dogs had recovered. One hundred and nine interdigestive complexes were studied in detail in five of the dogs during period ranging from 5 to 14 months. All observations were made while the dogs were healthy, conscious, and fasted. 3. The period of intense action potential activity, the activity frot or band, was found to be one phase of a cyclic‐recurring sequence of changes in action potential activity. The entire sequence, composed of four phases, occured almost simultaneously in the stomach and duodenun and then migrated distally in sequence over the entire small bowel. As one cycle terminated in the distal ileum, another had started in the stomach and duodenum, and this cyclic recurrence continued during fasts of 4 and 5 days. 4. The cycles of the interdigestive complex tended to recur at the same time each day in three of the dogs. The mean periods of the cycles ranged from 90 to 114 min, and the mean time of their propagation from stomach to terminal ileim ranged from 105 to 134 min. The mean velocity of the activity fronts (phase III of the cycles) was 5‐7‐11‐7 cm/min in the orad portion of the small bowel and 0‐9‐2‐5 cm/min in the distal half. The mean calculated length of the activity front diminished from a range of 42–62 cm in the duodenum to 5‐10 cm in the ileum. 5. Intragastric instillation of 400 ml. milk always interrupted the complex present in the bowel at the time of instillation and usually suppressed the next, whereas 400 ml. saline solution interrupted the complex present in the bowel only at the time of instillation. Distension of the stomach with a ballon always suppressed the interdigestive complex in the stomach and duodenum but sometimes failed to interrupt its migration along the bowe.

This study was done to determine the comparative effectiveness of burimamide and metiamide as antagonists of gastric secretion stimulated by histamine and its methyl derivatives, Nalpha-methylhistamine, N-alpha,N-alpha-dimethylhistamine and 4-methylhistamine, in dogs with vagally denervated (Heidenhain pouches) and vagally innervated gastric mucosal septal pouches (Pavlov-type pouches). The secretagogues were always given by continuous i.v. infusion to produce steady states of secretory activity in the fasted conscious dogs; the antagonists were given by either rapid "bolus" i.v. injection or continuous i.v. infusion. With bolus injections, both antagonists promptly inhibited the secretion produced by histamine and its methyl derivatives. When control secretory rates were similar, 40 mumol of burimamide per kg and 4 mumol of metiamide per kg produced the same degree of inhibition. When the antagonists were also given by continuous i.v. infusion, the difference between them was greater, metiamide being 15 to 17 times more potent than burimamide. The effectiveness of the antagonists was not changed by vagal denervation. Symptoms of toxicity to burimamide developed at doses in excess of 30 mumol/kg/hr; none occurred with doses of metiamide ranging from 1.8 to 7.5 mumol/kg/hr.