Dog Stomach Research Articles

Regulation of oxygen uptake in resting and pentagastrin-stimulated canine stomach.

The relation between oxygen uptake and blood flow in the isolated dog stomach was investigated under resting conditions and during intra-arterial infusion of isoproterenol or pentagastrin. Blood flows above and below control values were achieved by pump perfusion and partial arterial occlusion, respectively. In the resting stomach oxygen uptake increased from 0.4 to 1.5 ml.min-1.100 g-1 as blood flow increased from 4 to 40 ml.min-1.100 g-1 and then remained constant for blood flows up to 100 ml.min-1.100 g-1. Isoproterenol did not significantly alter the relation between oxygen uptake and blood flow. In pentagastrin-stimulated stomachs oxygen uptake was maintained at 2.5 ml.min-1.100 g-1 at blood flows between 40 and 100 ml.min-1.100 g-1 and decreased at blood flows below 40 ml.min-1.100 g-1. The results indicate that pentagastrin increases oxidative metabolism in the stomach. Despite this increase in oxygen consumption with pentagastrin, the general shape of the relation between blood flow and oxygen uptake remained the same and was simply displaced vertically above the control data.

Measurement of canine gastric vascular permeability to plasma proteins in the normal and protein-losing states

An isolated segment of the greater curvature of a dog's stomach was perfused at constant flow through a single cannulated artery with donor blood containing 131I-albumin, 125I-fibrinogen, and papaverine. Perfusion pressure was 30–50 mmHg, and venous pressure was set at 15 mmHg. Venous blood was collected in 1-min samples for 60 min. Filtration of fluid and loss of labeled proteins were calculated as the difference between measured arterial inflow and venous outflow. Permeability-surface area products (PS) were calculated for the proteins, and reflection coefficients (σ) were calculated from solute flux and filtration. Intraarterial infusion of histamine (1.6–1.9 μg · ml−1) increased filtration and PS and decreased σ for albumin but not fibrinogen. When protein-losing was established by topical irrigation with 10 mM dithiothreitol in neutral solution, filtration and PS increased, and σ for albumin but not fibrinogen decreased. Irrigation of the mucosa with 10 mM salicylic acid in 100 mN HCl caused bleeding that was quantitated by addition of 51Cr-erythrocytes to perfusing blood. Filtration and PS increased, and σ for albumin but not fibrinogen decreased. Hematocrit of blood lost remained low during extensive mucosal damage. Effects of histamine infusion were attenuated or abolished by cimetidine (4 mg · kg−1 loading, 1.4 mg · kg−1 · h−1 continuous infusion) or by pyrilamine maleate (5 mg · kg−1 bolus injection at beginning of irrigation, repeated at 40–50 min). Pyrilamine attenuated or abolished effects of topical dithiothreitol or salicylic acid. We conclude that during protein loss caused by dithiothreitol or salicylic acid, histamine released within the mucosa causes increased vascular permeability for plasma proteins.

Role of H2-receptors in gastrogenic hyperglycemia and hyperinsulinemia in dogs.

Recent studies have demonstrated that an acidified liver meal stimulates insulin release and raises plasma glucose levels. To examine the mechanism of these changes, a liver extract test meal at either pH 7 or at pH 2 was instilled into the stomach of dogs with a bisected pylorus and a gastric fistula during the infusion of either cimetidine, a specific H2-receptor antagonist, or a saline control. In response to the meal at pH 2 insulin, glucagon and glucose levels rose significantly and were not significantly changed by the infusion of cimetidine. In response to the liver meal at pH 7 a late rise in plasma glucagon levels was observed while plasma insulin and glucose did not change significantly; however, during the infusion of cimetidine a significant rise in plasma insulin and glucose levels occurred. The present data suggest that H2-receptors participate in an inhibitory mechanism with respect to the insulin and glucose response during the gastric phase of a neutral meal, but they do not seem to be involved in the rise in insulin and glucose observed in response to an acidified gastric meal.

In vivo stability of nitrite and nitrosamine formation in the dog stomach: effect of nitrite and amine concentration and of ascorbic acid.

Formation of N-nitrosodimethylamine (NDMA) from the precursors nitrate and dimethylamine has been studied in the chronically fistulated dog stomach. Measurements have also been made as a function of time for nitrite stability and gastric pH, and a nonabsorbable marker has been used to correct for gastric emptying and dilution. In the fasting animal NDMA forms within minutes after addition of the reactants if the pH is below 5. The presence of food in the stomach slows the reaction, and the additional presence of ascorbic acid greatly depresses the amount of NDMA formed. The concentration of nitrite in gastric juice declines rapidly after its introduction, but the concentration of NDMA declines even more rapidly than nitrite. This suggests that NDMA is probably rapidly absorbed directly from the dog stomach, in contrast to earlier results in rodent experiments.

Permeability of gastric capillaries to small and large molecules.

The permeability of capillaries in the stomach to small and large solutes was studied with the double-indicator diffusion technique in the dog stomach and by analysis of steady-state lymph and plasma samples in the cat stomach. The effective pore radius in gastric capillaries determined by indicator diffusion was 53 A, whereas steady-state lymph samples predicted a small-pore radius of 47 A. At the highest plasma flow rates studied (achieved by intra-arterial infusion of isoproterenol), indicator diffusion estimates of the permeability-surface area product for raffinose, inulin, and beta-lactoglobulin A were 140, 70, and 8 ml . min-1 . 100 g-1, respectively. The lymph studies indicate that gastric capillaries are more permeable than capillaries in the intestine and colon to albumin and larger molecules. The calculated effective large-pore radius of gastric capillaries was 250 A. The osmotic reflection coefficients (sigma d) ranged from 0.73 +/- 0.03 for albumin to 0.91 +/- 0.02 for beta-lipoprotein (120-A radius). The sigma d for total plasma protein was 0.78 +/- 0.03, indicating a substantial transcapillary oncotic pressure gradient, despite the greater permeability of these capillaries for macromolecules.

Catecholamines and the cephalic phase of gastric secretion

Methoxamine, an α-adrenergic agent, and isoproterenol, a β-adrenergic agent, significantly augmented indirect vagally stimulated (intravenous 2-deoxy-D-glucose) acid and pepsin secretion from the main stomachs of conscious dogs. Heidenhain pouch secretion in the same dogs was unaffected.

Effect of pentagastrin on periodic activity of the stomach and duodenum in dogs with intact and disturbed gastric innervation

Effect of pentagastrin on periodic activity of the stomach and duodenum in dogs with intact and disturbed gastric innervation

Inhibition by somatostatin of carbamylcholine-induced gastrin and glucagon release from the isolated perfused canine stomach.

At an arterial plasma concentration of 61 nmol/l (100 ng/ml) synthetic cyclic somatostatin completely abolished basal glucagon and gastrin release as well as carbamylcholine-induced glucagon and gastrin release from the isolated perfused dog stomach. These observations are compatible with the view that endogenous somatostatin previously reported to be released during vagal stimulation might be involved to explain the lack of gastric-glucagon response in this situation. They do not, however, rule out the alternative proposal that the dog fundic A-cell may simply be a non-innervated cell.

Comparative study of G- and D-cell population in the dog stomach.

Since somatostatin is a local hormone controlling gastric acid secretion and gastrin release, quantitative histopological distribution of the G-cells and D-cells in the canine whole stomach was investigated by the specific immunoperoxidase staining technique. The G-cells were identified only in the pyloric antrum and the estimated total number of G-cells was 15.5 X 10(6) cells. Most of the D-cells were also found in the pyloric antrum but a few were found scattered diffusely throughout body and fundus of the stomach. The estimated total number of D-cells was 11 X 10(6) cells in the pyloric antrum and 4 X 10(6) cells in the corpus and fundus. The G-/D-cell ratio in the antrum was 1.4:1. The number of G-cells as well as D-cells per unit mucosal surface area was significantly higher on the greater curvature and the proximal part of the antrum than on other areas of the antrum. Thus, the pattern of distribution in G-cells was similar to that of D-cells and there was a highly significant correlation between G- and D-cells per unit mucosal surface area. It would appear that under normal conditions, the number of G- and D-cells in the antrum are in good balance and may play an important role in the control mechanisms related to gastric secretion.

Autoregulation of gastric blood flow and oxygen uptake.

The purpose of this study was to determine whether the ability of the stomach to autoregulate blood flow and oxygen uptake is altered by sympathetic denervation. Blood flow, oxygen extraction, local arterial pressure, and venous pressure were continuously monitored in sympathetically innervated and denervated autoperfused dog stomach preparations. As perfusion pressure was reduced in increments from 120 to 20 mmHg in innervated preparations, blood flow and oxygen uptake decreased while oxygen extraction and vascular resistance increased. Reductions in perfusion pressure in denervated preparations resulted in a decrease in blood flow, oxygen uptake, and vascular resistance, whereas oxygen extraction increased. The ability of the stomach to regulate blood flow and oxygen uptake was significantly improved after denervation, i.e., vascular resistance decreased and oxygen uptake remained relatively constant when arterial pressure was reduced. Oxygen uptake in denervated stomachs was generally higher than that in innervated stomachs. Autoregulation of gastric blood flow therefore appears to be improved by denervation. The better autoregulation observed after denervation may result either from a reduction in sympathetic tone and/or the increase in gastric oxygen demand.

Glyceroglucolipids of the mucous barrier of dog stomach

Distribution of glyceroglucolipids in the mucous barrier of dog stomach fundus, body and antrum was investigated. Surface mucus lining and preformed intracellular mucus were obtained by instillation of the ligated stomach compartments with 2 M NaCl. Lipids were extracted from the dialyzed and lyophilized samples, and the glycolipids were separated into neutral and acidic fractions. The glyceroglucolipids contained in each fraction were purified into individual components by thin-layer chromatography and were quantified. The content of glyceroglucolipids (μmol glucose/g protein) in the antral portion of the stomach was 2.1 times greater than that of the fundus and 3.4 times greater than that of the body. All three areas of the stomach contained neutral and sulfated glyceroglucolipids. However, the level of sulfated glycerolglucolipids (μmol glucose/g protein) was three times higher in the antrum as compared to the fundus and four times higher as compared to the body. The neutral and sulfated glyceroglucolipids were present in a molar ratio of 1.0 : 0.7 in the fundus 1.0 : 1.1 in the body, and 1.0 : 1.5 in the antrum.

Size of liver particles emptied from the human stomach

The canine stomach empties meat as particles smaller than 0.5 mm. The present work was undertaken to determine whether fed liver enters the human intestine predominantly as small particles. In both human and canine subjects, a triple lumen (OD = 4 mm) tube was positioned with the ports beyond the ligament of Treitz, two attached to a Crosby bubble trap with 1.2-mm holes. The bubble trap effectively sampled only particles smaller than 0.8 mm. Polyethylene glycol and 0.1–0.5-mm particles of 51Cr-chicken liver were perfused at a constant rate through the 3rd port, 25 cm proximal to the bubble trap. It was assumed that small particles of liver entering the perfused segment from above would be sampled in the same proportions as the perfused 51Cr-liver particles, so the amount passing the bubble trap could be calculated from recovery of 51Cr. Both dogs and humans were fed 60 g of steak + 30 g of 99mTc-chicken liver in 10 mm cubes, + 100 ml H2O. In validation experiments in dogs and humans, there were good correlations between calculated recovery from the bubble trap and actual recovery. In humans, the rate at which aspiratable (<1.0 mm) particles of fed 99mTc-chicken liver passed the bubble trap was compared with the rate at which 99mTc-chicken liver particles of all sizes entered the bowel, as determined by measuring gastric emptying of 99mTc with a gamma camera.When 5 human subjects were fed 10-mm cubes of 99mTc-chicken liver, 76 ± 7% of the liver left the stomach in 3 h, while 72 ± 5% passed the jejunal sampling site as aspirable particles. When the same subjects ate the liver as aspiratable, 0.4-mm particles on another day, 66 ± 8% left the stomach in 3 h, while 58 ± 4% passed through the jejunum as aspiratable particles. By contrast, when 1.2–1.7-mm particles of 99mTc chicken liver were instilled into the proximal duodenum, little liver could be aspirated from the jejunum. The findings indicate the human stomach, like the dog stomach, allows only small particles of meat to pass into the gut.

NdYAG laser photocoagulation in the dog stomach.

Considerable discussion still centres around the relative merits of the Argon and Neodymium Yttrium Aluminum Garnet (NdYAG) lasers for the endoscopic treatment of gastrointestinal haemorrhage, although both are undoubtedly effect. We have carried out experiments to elucidate which factors determine the safety and efficacy of NdYAG laser photocoagulation. Histological studies on normal gastric mucosa showed that the depth of tissue damage depended mainly on the total incident laser energy, whereas the effectiveness of photocoagulation of induced gastric ulcers in heparinised animals depended on the laser power and the exposure time used. Optimum haemostasis with minimum tissue damage was obtained using pulses of 300 to 500 ms duration with energies of 25 to 40 J. We consider these parameters safe and effective for use in pilot clinical studies.

Release of vasoactive intestinal peptide by distention of the proximal stomach in dogs.

The effect of transient proximal gastric distention was studied in six conscious dogs previously submitted to antrectomy and Billroth I anastomosis (and in which the intragastric pH was not altered), and in five anaesthetised dogs prepared with an innervated acute fundic pouch in which the pouch lumen was acidified with 0.15 M hydrochloric acid. Levels of vasoactive intestinal peptide (VIP) in portal and peripheral plasma were measured by radioimmunoassay. In conscious antrectomised dogs, distention of the proximal stomach to volumes of 250 and 500 ml evoked a significant rise of portal VIP concentration, with a maximal variation of 32.7 +/- 4.4 to 67.7 +/- 14.8 pg ml-1, which was hardly reflected in systemic blood. In the anaesthetised dogs, transient distention of the acute fundic pouch with 0.15 M hydrochloric acid under a pressure of 40 cm of water elicited a significant rise of portal VIP from 36.2 +/- 8.9 to 59.8 +/- 12.4 pg ml-1 (P < 0.05) without any significant variation of the peptide concentration in peripheral plasma. These results indicate that vasoactive intestinal peptide is released under transient proximal gastric distention in dogs, and that this response is not solely dependent upon the acid secretory effect of distention in this species.

Neurotransmitters and glucagon release from the isolated, perfused canine stomach.

The isolated, perfused, canine stomach was used to investigate the effect of three neurotransmitters--norepinephrine, acetylcholine (or its analogue carbamylcholine), and VIP (vasoactive intestinal peptide)--on gastric glucagon release. Norepinephrine at the two concentrations tested (3.10-8 and 7.10-7 M) did not influence gastric glucagon release. In contrast, acetylcholine or carbamylcholine (5.10-6 M) as well as VIP (46-60 ng/ml) unequivocally stimulated gastric glucagon release, an effect apparently independent of the changes in blood flow. These results are in sharp contrast with the previously reported lack of effect of an electric stimulation of the vagus nerves on the release of glucagon from the dog stomach. An absence of innervation of the canine gastric A-cell would probably best explain this situation.

Topical effects of 16,16-dimethyl prostaglandin E2 on gastric blood flow in dogs.

The effects of luminal instillation of 16,16-dimethyl prostaglandin E2 (dmPGE2) on total gastric blood flow and its fractional distribution between the layers of gastric tissue were determined in exteriorized segments of the greater curvature of dog stomach. Total gastric blood flow was measured simultaneously by venous outflow and alpha-labeled microspheres; both methods correlated well with each other (r = 0.88, P less than 0.01). In the nonstimulated stomach, dmPGE2 caused an increase in total gastric blood flow from 4.2 +/- 0.8 to 7.4 +/- 1.2 ml/min (P less than 0.05). In contrast, dmPGE2 significantly reduced gastric blood flow in histamine-stimulated stomach (from 14.6 +/- 1.2 to 9.2 +/- 1.0 ml/min; P less than 0.01). The changes in mucosal blood flow ere proportional to the alterations in total blood flow because the fractional distribution of blood flow to the mucosa remained relatively unchanged during dmPGE2 administration. These observations suggest that dmPGE2, a known vasodilator, induces an increase in gastric blood flow in the resting stomach, whereas it reduces gastric blood flow in the actively secreting stomach as a result of secretory inhibition.

Gastric inhibitory polypeptide (GIP) is not the primary mediator of the enterogastrone action of fat in the dog

We compared the inhibition of food-stimulated gastric acid secretion and changes in serum concentrations of immunoreactive gastric inhibitory polypeptide and gastrin caused by: (a) duodenal perfusion of oleic acid, and (b) intravenous infusion of pure, natural, porcine gastric inhibitory polypeptide in dogs with gastric fistula and pancreatic fistula. A rate of duodenal perfusion of oleic acid (12 ml/hr) which gave near maximal pancreatic protein response was chosen. This dose of oleic acid caused complete suppression of acid response to a meal of liver extract (300 ml of a 15% solution) while elevating serum immunoreactive gastric inhibitory polypeptide modestly. By contrast, intravenous administration of gastric inhibitory polypeptide that raised serum immunoreactive gastric inhibitory polypeptide several fold caused only 40% inhibition of acid response to the same meal. Other effects of duodenal perfusion of oleic acid were exaggeration of pancreatic protein secretion and significant inhibition of gastrin release in response to the meal. Exogenous administration of gastric inhibitory polypeptide, on the other hand, was without significant effect on these responses. These results suggest that, in the innervated dog stomach, the enterogastrone action of fat is not primarily mediated by gastric inhibitory polypeptide.

Effects of regional hypercalcemia on gastric acid secretion

The effect of regional hypercalcemia on histamine-induced gastric acid secretion from chambered fundic segments was studied in five anesthetized mongrel dogs. This preparation allowed direct infusion of calcium into the nutrient artery of the gastric segment whereby venous effluent calcium levels were maintained in excess of 14 mg%, while systemic calcium levels were within a normal range. Blood flow, as measured by a venous effluent technique, did not change. Acid secretion decreased from 43.03 ± 7.13 to 12.20 ± 5.72 μEq/min during calcium infusion and rose to 37.04 ± 3.83 μEq/min when the infusion was terminated. These results provide clear evidence that calcium has a direct and reversible inhibitory effect on histamine-induced parietal cell secretion from exteriorized fundic segments of dog stomach.

Gastro-gastric excitatory motor reflex in the dog.

Lowering of the intra-antral pressure caused enhanced movements of the corporal pouch in the dog stomach. Stimulation of the central end of vagal fibers supplying the antrum also augmented movements of both the antral pouch and corporal pouch. The findings suggest the existence of a gastro-gastric excitatory reflex which plays a role in gastric emptying.

Sympathectomy and prostaglandin deficiency do not prevent gastrogenic hyperglycaemia and hyperinsulinaemia.

To examine the mechanism of the recently reported effect of an acidified intragastric test meal on insulin release and glucose homeostasis, a liver extract test meal at either pH 2 or pH 7 was instilled into the stomach of normal dogs and dogs with a chemical sympathectomy or indomethacin-induced prostaglandin deficiency, all of which had a bisected pylorus and gastric fistula. In the normal dogs the instillation of the liver meal at pH 2 elicited a significant rise in plasma glucose, glucagon and insulin levels, while in response to the meal at pH 7 only glucagon rose significantly. This was not altered in chemically sympathectomized dogs, nor during the infusion of indomethacin. In all experiments gastrin or gastric glucagon release in response to the meal at pH 2 was either lower than or similar to the response to the meal at pH 7. These data suggest that the influence of the stomach upon islet cell function and glucose homeostasis does not depend on either adrenergic innervation or the presence of prostaglandings, but rather is mediated by a yet undetermined mechanism.