Canine Duodenum Research Articles

Motilin regulation of canine interdigestive intestinal motility.

The objective was to determine whether motilin regulates cyclical interdigestive motility in the jejunum as well as in the duodenum. In four conscious dogs with an intact innervated duodenum, an autotransplanted (extrinsically denervated) 75-cm loop of proximal jejunum, and an autotransplanted, in situ distal jejunum, interdigestive myoelectrical complexes cycled independently in all three regions of small bowel. Plasma concentration of motilin was greater during phase III of the duodenal cycles (304 +/- 37 pg/ml) than during phase I (235 +/- 37 pg/ml) or phase II (235 +/- 39 pg/ml; P less than 0.05), but the concentration did not vary consistently with the phases of the cycles in the autotransplanted jejunal segments. Intravenous infusions of motilin (0.6 microgram/kg/min for 5 hr), begun 15-30 min after passage of phase III through the duodenum, shortened the interval between phase IIIs in the duodenum from 147 +/- 14 min before infusions to 44 +/- 3 min during the infusions (P less than 0.05), but did not alter consistently the interval between phase IIIs in the autotransplanted jejunal segments. Feeding decreased plasma motilin concentration. The data were consistent with motilin regulation of interdigestive motility in intact, innervated canine duodenum but not in extrinsically denervated jejunum.

Gastrin in duodenal and jejunal tissue and in plasma following antrectomy with gastrojejunostomy.

The number of gastrin‐immunoreactive cells in the duodenum was assessed by immunohis‐tochemistry in 10 dogs that had been subjected to antrectomy with gastroduodenostomy (Billroth I), in 4 dogs in which an antrectomy with gastrojejunostomy (Billroth II) had been performed and in 4 unoperated controls. Gastrin‐immunoreactive cells were found only in dogs that had been subjected to antrectomy ad modum Billroth I and then only within the first 30 mm of the duodenum, i. e. in the duodenal bulb. The gastrin cells occurred scattered on the villi, in the crypts and within the glands of Brunner. In 3 of the dogs patches of antral‐type mucosa occurred within the first 10 mm of the duodenum. All dogs in which gastrin‐immunoreactive cells were found have in a previous study been shown to have a markedly increased tissue concentration of gastrin in the proximal third of the duodenum compared to unoperated controls. In the dogs subjected to antrectomy ad modum Billroth II in which no cells were observed the level of gastrin in duodenal tissue has been found to be moderately elevated compared to that of control dogs. The results indicate that the increased gastrin concentration in the proximal third of the duodenum following antrectomy ad modum Billroth I corresponds to an increase in the number of gastrin‐immunoreactive cells in the duodenal bulb.

The effect of antrectomy on the number of gastrin-immunoreactive cells in the canine duodenum.

The number of gastrin-immunoreactive cells in the duodenum was assessed by immunohistochemistry in 10 dogs that had been subjected to antrectomy with gastroduodenostomy (Billroth I), in 4 dogs in which an antrectomy with gastrojejunostomy (Billroth II) had been performed and in 4 unoperated controls. Gastrin-immunoreactive cells were found only in dogs that had been subjected to antrectomy ad modum Billroth I and then only within the first 30 mm of the duodenum, i.e. in the duodenal bulb. The gastrin cells occurred scattered on the villi, in the crypts and within the glands of Brunner. In 3 of the dogs patches of antral-type mucosa occurred within the first 10 mm of the duodenum. All dogs in which gastrin-immunoreactive cells were found have in a previous study been shown to have a markedly increased tissue concentration of gastrin in the proximal third of the duodenum compared to unoperated controls. In the dogs subjected to antrectomy ad modum Billroth II in which no cells were observed the level of gastrin in duodenal tissue has been found to be moderately elevated compared to that of control dogs. The results indicate that the increased gastrin concentration in the proximal third of the duodenum following antrectomy ad modum Billroth I corresponds to an increase in the number of gastrin-immunoreactive cells in the duodenal bulb.

Motilin-independent ectopic fronts of the interdigestive myoelectric complex in dogs.

We have studied in four conscious dogs the relationship between circulating concentrations of motilin and the activity front (phase III) of the interdigestive myoelectric complex. During fasting, cyclic peaks of motilin secretion were concomitant in every instance with the initiation of activity fronts that began in the stomach or duodenum. When somatostatin was administered at doses of 5, 2.5, or 0.625 microgram x kg-1 x h-1 for 3 h, motilin concentrations were stabilized at lowered levels and no activity fronts occurred in the duodenum. Somatostatin also inhibited the stimulatory effects of exogenous motilin on the entire small intestine. During somatostatin infusion, however, ectopic fronts began in the jejunum and were propagated to the cecum despite low motilin concentration. After a 100-g meat meal, the cyclic increase of motilin was interrupted and no activity fronts were observed in the duodenum, but ectopic fronts started lower in the small intestine. Our study supports the hypothesis that motilin induces activity fronts in the canine duodenum, but it shows that ectopic fronts are not controlled by motilin.

Species Difference in GI Motor Response to Somatostatin

Acute experiments were performed on overnight fasted chloralose‐urethan anesthetized dogs, cats, rabbits, and rats. Under these conditions, somatostatin practically abolished gastric contractions and decreased GI tonus in all species examined. The canine duodenum, jejunum, and ileum exhibited only a contractile response to somatostatin, whereas motor activities of the small intestines of the cat, rabbit, and rat were inhibited. In all instances and at all dosages, both the inhibitory and excitatory effects showed suggestions of tachyphylaxis. The data also indicate that excitatory or inhibitory effects were not dependent on the presence of long arc pathways. It is concluded that somatostatin exerts a direct stimulatory effect on the canine small intestine that is mediated by the muscularis mucosa.

Radioimmunoassay of motilin. Validation and studies on the relationship between plasma motilin and interdigestive myoelectric activity of the duodenum of dog.

A radioimmunoassay method of motilin was developed in our laboratory and was validated in dogs with a platinum monopolar electrode in the duodenum. We confirmed that a bolus infusion of 0.3 M tris-buffer solution or 0.1 N HCl solution in the duodenum produces a significant rise in plasma immunoreactive motilin (IRM) concentrations. This coincided with a marked increase in the percentage of spike potentials on slow waves of the duodenum, similar to phase III of interdigestive myoelectric-activity (MA). A possible relationship between plasma IRM and interdigestive MA of canine duodenum was studied. It was found that cyclic changes occurred in the fasting plasma IRM concentrations in dogs. While the peak motilin concentration was always observed in phase III, the lowest concentration of motilin was found in phase I of interdigestive MA in the duodenum. In dogs with the electrodes in the duodenum and jejunum, the peak IRM concentration did not correlate with phase III of interdigestive MA in the jejunum. A dose of synthetic porcine motilin, 0.06 μg/kg/hr, which produced the plasma IRM concentration comparable to the peak fasting motilin concentration, could induce an identical phase III in the duodenum. These observations indicate that there is a relationship between cyclic changes in plasma IRM concentrations and interdigestive MA of the duodenum. It is suggested further that motilin is a hormone which may play an important role in inducing phase III of interdigestive MA in the duodenum.

Effect of electrocoagulation on canine esophagus, stomach and duodenum

Effect of electrocoagulation on canine esophagus, stomach and duodenum

Acid Absorption in the Canine Duodenum

Alterations in composition of isosmotic acid solutions were studied in exteriorized segments of the proximal (Brunner's gland area) and distal canine duodenum, mounted in lucite chambers. Varying concentrations of HCl (40, 80, 120, 160 mEq/l) made isotonic by the addition of NaCl were instilled into the chamber, removed in 15 minutes and analyzed for volume, electrolytes, protein content and osmolality. Both proximal and distal duodenal mucosa modified the instilled solution with a loss of H+ and a gain in Na+ and K+, which occurred at similar rates independent of the acid concentration of the instilled solution. The rate of ionic movement was twice that for the antrum, and 30-100 times that of the fundus. Calculated H+ loss across the entire duodenal mucosa at these rates could account for 17.5% of the peak acid output from the canine stomach. The loss of H+ could not be accounted for on the basis of neutralization and probably represented transmucosal insorption. In addition to the neutralization of gastric acid by pancreatic juice and bile, duodenal mucosa thus plays an important role in the maintenance of intraluminal pH. Duodenal mucosal permeability to H+ may be related to the vulnerability of the duodenal mucosa to acid-peptic ulceration.

Depression of pancreatic bicarbonate response during endotoxic shock in dogs

Upper gastrointestinal erosions have been a significant clinical finding subsequent to septic or endotoxic shock. Gastric acid as an integral factor in the stress ulcer syndrome is crucial to the formation of acute gastric erosions both in man [8] and in the dog [4]. Recent experiments have demonstrated that endotoxin-induced shock severely reduces the ability of the canine proximal duodenum to clear or neutralize hydrochloric acid (HCl) [21. The two main mechanisms by which HCl is cleared from the duodenum are neutralization by pancreatic bicarbonate (HCO,), and transmural absorption of the hydrogen ion [9]. Greenberg and Himal [2] noted a significant decrease in both the amount of hydrogen ion lost transmurally and in the amount neutralized and diluted by mixed bile and pancreatic juice secretions in canine duodenal pouches during endotoxic shock. This decreased clearance was associated with the formation of acute duodenal erosions. The following experiments were done with the intent of quantitating the role of the pancreas in the neutralization of HCl during endotoxic shock in dogs.

Electrical spike potentials of the small bowel: A comparative study of recordings obtained from muscular implanted and intraluminal suction electrodes

Electrical spike potentials from the canine duodenum have been recorded from intramuscular implanted and intraluminal suction electrodes. There was a significantly greater amplitude of the spike potentials recorded from implanted electrodes, otherwise the potentials were identical in number, duration and time of onset. Thus spike potentials recorded from suction electrodes, as used in clinical motility studies, accurately represent the event within the muscular layer.

Effect of Gastric Hypersecretion on the Canine Duodenum

The neutralization of acid introduced into the duodenum has been found to be less intensive in patients with duodenal ulcer than in controls. The present work studied the possibility that chronic gastric hypersecretion injures the duodenal mucosa and thereby influences the neutralization system. Gastric hypersecretion was provoked for 3 weeks in 3 dogs by a daily injection of a gastrin preparation with prolonged effect. After a subcutaneous injection of this preparation given together with a test meal the acidity of both gastric and duodenal contents was found to increase significantly. After the 3 weeks of gastric hypersecretion the pancreatic bicarbonate response to exogenous secretin was unchanged, while the bicarbonate response to duodenal acidification was decreased from 2.03 mEq/30 min to 1.27 mEq/30 min (p less than 0.05), compatible with an impaired secretin release. Also the concentration of lactase, maltase, sucrase, and alkaline phosphatase in mucosal biopsies from the second part of the duodenum was significantly reduced (p less than 0.001). These results indicate that gastric hypersecretion causes mucosal damage in the duodenum and thereby reduces the release of secretin.

Gastric inhibitory polypeptide (GIP)

Radioimmunoassayable gastric inhibitory polypeptide was measured in extracts of canine antrum, duodenum, jejunum, and ileum. The highest GIP concentrations were found in the duodenum (347 +/- 53 ng/g) and jejunum (300 +/- 68 ng/g). An immunochemical similarity was demonstrable between porcine GIP and canine GIP. Dogs prepared with Mann Bollman fistulae were given an amino acid (AA) mixture or medium-chain triglycerides (MTC) by intraduodenal perfusion. With AA, a peak mean serum concentration of 672 +/- 106 pg/ml was reached 15 min after starting the perfusion. MCT resulted in a peak mean serum GIP concentration of 504 +/- 55 pg/ml 30 min after beginning the perfusion. When compared to results previously reported from this laboratory, AA and MCT are not as potent as corn oil (long-chain triglyceride) or glucose in stimulating GIP release. We conclude: (1) Immunoassayable GIP concentrations are highest in the canine proximal small intestine. (2) AA and MCT are weak stimulants of GIP release in the dog.

Mechanisms of acid disposal in canine duodenum

Distal duodenal pouches chronically excluded from the intestinal stream were perfused in seven awake dogs by a constant-circulation technique using isomolar solutions containing 60-120 mM HCl. The rate of disappearance of hydrogen ions (H+) and net ion movements was measured. In all experiments there was a loss of H+ from the perfusate accompanied by a gain of sodium (Na+), potassium (K+) and chloride (Cl-), together with an increase in volume and a decrease in osmolality. The magnitude of this H+ loss was a function of instillate [H+]. The H+ lost by neutralization was separated from that lost by diffusion by calculations based on the assumption that the observed changes in somolality were the result of neutralization by bicarbonate (HCO3-). The bulk of the acid (67%) was lost by neutralization, the remainder back-diffusing in a one-to-one exchange for diffusable Na+. This ability to dispose of acid decreased with increasing age of the pouches due to a diminished volume of HCO3- secretion, the magnitude lost by backdiffusion remaining unchanged.

Hydrolysis of amino acid amides of dopamine by extracts of animal tissues

An investigation was made of the in vitro hydrolysis of numerous amides of dopamine (DA) and its α- or O-methylated derivatives with α-amino acids. These amides were hydrolyzed by aminoacylarylamidase, and they exhibited a wide spectrum of hydrolysis rates when incubated at pH 6.9 with the particulate fraction of renal homogenates. l-Alanyl-DA ( l-ADA) was the most rapidly hydrolyzed of all the amides tested with canine kidney, and the l-alanyl amide of each derivative of DA was also preferentially hydrolyzed. Relative rates ranged from a value of 1.000 for l-ADA to 0.002 for l-prolyl-DA; very few amides were not hydrolyzed at all. Amidase activity against l-ADA was very high in the small intestine and kidney; plasma contained less activity and that of other tissues was negligible. When tested against a small series of DA-amides, amidase preparations of canine duodenum, kidney, and plasma showed identical specificities. Species differences do exist, however, because crystalline renal arylamidase of the pig and unpurified renal amidases of the rat, dog, monkey and human showed minor differences in substrate specificity.

Effect of Escherichia coli on fluid transport across canine small bowel. Mechanism and time-course with enterotoxin and whole bacterial cells.

An Escherichia coli strain isolated from a patient with severe cholera-like diarrhea elaborates a partly heat-labile enterotoxin shown to cause prompt adenyl cyclase stimulation and isotonic fluid secretion by canine jejunum. Both responses disappear upon removal of the enterotoxin. The duration of action of a submaximal dose of this E. coli enterotoxin was brief, despite sustained exposure to the jejunum, suggesting inactivation of the enterotoxin by its interaction with the mucosa. Inoculation of whole bacterial cultures of this E. coli strain into canine duodenum was followed by bacterial survival and induction of net secretion after 4-7 h. The onset of fluid production was associated with increasing gut mucosal adenyl cyclase activity. Washed bacterial cells could also produce fluid secretion. In vivo multiplication of this enterotoxin-producing E. coli was demonstrated 6-12 h after intraduodenal inoculation of approximately 10(6) organisms. This was associated with fluid secretion. Intestinal fluid production occurred without microscopic pathology in the mucosa.

Immunofluorescent localization of secretin in the canine duodenum

The endocrine polypeptide (APUD) cells responsible for the production and storage of secretin have been demonstrated, in canine duodenum, by the application of an indirect immunofluorescence technique, using anti-pure porcine secretin, to carbodiimide-fixed cryostat sections. The cells are identified, by the use of parallel cytochemical and ultrastructural preparations, as the small granular S cells. These are essentially restricted to the transitional zone of the duodenal mucosa, with whose lumen their apical projections probably always make contact. There is no need to alter the title of the cells since S can now stand for secretin instead of for small.

Failure of high PCO2 in the duodenal bulb to inhibit gastric acid secretion.

AbstractGastric acid secretion was stimulated by intravenous infusion of pentagastrin (ICI 50 123) in dogs with Pavlov pouches and isolated pouches of the duodenal bulb. Elevation of the Pco2 to 150 or 700 mm Hg in the bulbar pouches did not reduce the gastric acid output. It is suggested that the high CO2 tension which normally exists in the canine duodenum during periods of stimulated gastric acid secretion is not involved in the activation of the bulbar mechanism inhibiting the gastric acid secretion.

Fluid dynamics in volumogenic diarrhea.

A study was performed to evaluate motility patterns and the role of intestinal sphincters in a diarrhea model. Fluid was infused into the canine duodenum to produce diarrhea. We discerned 4 patterns of action in the development of volumogenic diarrhea: 1. the anal sphincter was open and the ileocecal sphincter prevented diarrhea, 2. the ileocecal and anal sphincters acted independently both preventing diarrhea to some extent, 3. the ileocecal sphincter was open and the anal sphincter prevented diarrhea, and 4. diarrhea occurred when the ileocecal sphincter was closed because of spontaneous colonic motility. Pattern 3 occurred most frequently. Duplication of these patterns was accomplished with a physical analogue constructed from Penrose tubing and clamps to simulate the intestines and the sphincters.

Response of the canine duodenum to intraluminal challenge with cholera exotoxin.

In response to intraluminal challenge with crude cholera exotoxin, canine Thiry-Vella duodenal loops consistently produced isotonic fluid for a 24-36 hr period. Isotonic fluid production generally began within 15 min after challenge. Mean bicarbonate concentration of fluid produced by duodenal loops was 24+/-6 (SD) mEq/liter. Perfusion of exotoxin-treated duodenal loops with an isotonic electrolyte solution containing glucose 60 mOsm/liter caused a significant decrease in exotoxin-induced isotonic fluid output. The net effects of glucose on isotonic fluid absorption by perfused duodenal loops were not significantly different before and after administration of crude cholera exotoxin. The response of canine duodenal loops to challenge by cholera exotoxin differs from responses of jejunal and ileal loops in a) absence of a detectable "lag period" between administration of exotoxin and initiation of net fluid output; b) a longer period of fluid production following exotoxin administration; and c) a significantly greater net fluid output per unit length of gut. The mean bicarbonate concentration of the fluid produced by duodenum is less than that produced by ileum, but is not significantly different from that produced by jejunum. The duodenal response is similar to that of the more distal small bowel segments in that an effect on isotonic fluid movement is observed shortly after exotoxin administration and the maximum rate of exotoxin-induced isotonic fluid production is not reached until 4-5 hr after exotoxin administration. The basis for the consistent delay of 4-5 hr between intraluminal exotoxin administration and maximum gut fluid production has not yet been determined. Current data are consistent with the hypothesis that the rate of secretion of isotonic fluid induced by cholera exotoxin is not significantly different per unit length, in duodenum and ileum and that the lesser net fluid output in the ileum is due to the greater capacity for isotonic fluid absorption by the more distal small bowel segment.

Extraluminal Contractile Force and Electrical Activity of Reversed Canine Duodenum

Extraluminal Contractile Force and Electrical Activity of Reversed Canine Duodenum