Canine Stomach Research Articles

Z-338 enhances acetylcholine release from the canine stomach in vivo microdialysis by blocking, muscarinic autoreceptors

Z-338 enhances acetylcholine release from the canine stomach in vivo microdialysis by blocking, muscarinic autoreceptors

Dye-enhanced selective laser ablation for surgical mucosectomy.

The diode laser operates at a wavelength of 805 nm; indocyanine green (ICG) has a maximum energy absorption of a wavelength of approximately 800 nm. The effect of the diode laser as a laser knife can be significantly enhanced with an injection of ICG. In the present study, this dye-enhanced photothermal effect was investigated in the field of surgical endoscopy. A 9-cm2 region of the canine gastric mucosa was removed by the laser after injection of 5 ml of ICG solution at a concentration of 0.5 mg/mL into the submucosal space. The diode laser was used at a power output of 10 watts. The canine stomach was removed 10 days after the operation to investigate the site histologically. Clinical application using transanal endoscopic microsurgery (TEM) was employed using a dye-enhanced laser in five patients with a rectal adenoma. The pathological changes in the canine gastric wall resected 10 days after the operation showed that the low-power laser enhanced by ICG produced less fibrosis in the submucosal space than electrocautery. Mucosal resection using a dye-enhanced laser was easily performed in these five patients. It was concluded that this easy removal of the mucosa by a dye-enhanced laser was due to its ability to produce hemostasis of the vessels and its excellent tissue-cutting effect.

Dye-enhanced Selective Laser Ablation for Surgical Mucosectomy

The diode laser operates at a wavelength of 805 nm; indocyanine green (ICG) has a maximum energy absorption of a wavelength of approximately 800 nm. The effect of the diode laser as a laser knife can be significantly enhanced with an injection of ICG. In the present study, this dye-enhanced photothermal effect was investigated in the field of surgical endoscopy. A 9-cm2 region of the canine gastric mucosa was removed by the laser after injection of 5 ml of ICG solution at a concentration of 0.5 mg/mL into the submucosal space. The diode laser was used at a power output of 10 watts. The canine stomach was removed 10 days after the operation to investigate the site histologically. Clinical application using transanal endoscopic microsurgery (TEM) was employed using a dye-enhanced laser in five patients with a rectal adenoma. The pathological changes in the canine gastric wall resected 10 days after the operation showed that the low-power laser enhanced by ICG produced less fibrosis in the submucosal space than electrocautery. Mucosal resection using a dye-enhanced laser was easily performed in these five patients. It was concluded that this easy removal of the mucosa by a dye-enhanced laser was due to its ability to produce hemostasis of the vessels and its excellent tissue-cutting effect.

Occurrence and characterization of gastric Helicobacter spp. in naturally infected dogs

Helicobacter-like organisms are frequently observed in the stomach of dogs but the relationship between these microorganisms and gastric pathology has not been clearly established. Different species of helicobacters are known to be present in the canine stomach but their specific prevalence in naturally infected dogs is unknown. The aims of this study were to isolate and characterize helicobacters in canine gastric biopsies, to compare the commonly used tests for the identification of Helicobacter spp. and to determine the occurrence of these species in dogs. Twenty-three out of 25 dogs (92%) were positive for Helicobacter-like organisms in cytological screening. Culture was successful from biopsies of 5/25 dogs. The isolates were analyzed by electron microscopy, biochemical and physiological tests, whole protein analysis and 16S rDNA sequencing. Helicobacter felis was identified in four samples and Helicobacter bizzozeronii in one sample. Only the whole protein analysis in combination with electron microscopy was able to clearly discriminate the two species. Compared to the high prevalence of Helicobacter-like organisms, the occurrence of H. felis and H. bizzozeronii, was low (17 and 4%, respectively). No Flexispira rappini-like organisms or H. salomonis were detected. Electron microscopy revealed that H. bizzozeronii-like microorganisms were present in three additional biopsies where we were unable to culture any Helicobacter-like organisms. These observations indicate that in the stomach of dogs not all helicobacters are culturable. The unculturable bacteria appeared to be the prevalent ones and may represent different spiral organisms. The presence of distinct helicobacters with different characteristics can reflect different roles in the pathogenesis of canine gastric disease.

Ultrastructure of the hydrophobic gastric surfactant barrier in the dog

To confirm the hydrophobicity of the luminal surface of the canine stomach and to elucidate the ultrastructure of the lining imparting that property. Gastric and duodenal mucosal samples from eight dogs were collected immediately after euthanasia and subjected to contact angle measurement using a goniometer. Other samples were examined by electron microscopy following a fixation procedure known to preserve phospholipids and oligolamellar structures. Contact angles for the canine gastric mucosal surface (85.1 +/- 5.5) were significantly greater (P < 0.0001) than for the duodenum (24.0 +/- 1.7). Electron microscopy revealed the existence of surfactant as abundant osmiophilic phospholipid material within the gastric and duodenal mucosae. We have confirmed the hydrophobic nature of the canine gastric mucosa whereas the luminal surface of the duodenum is hydrophilic. We propose that the water-repellent nature of the canine gastric lining contributes to the 'gastric mucosal barrier' and is imparted by an oligolamellar layer of surface-active phospholipid ('gastric surfactant') adsorbed to the surface. Both gastric and duodenal mucosae may also utilise phospholipids as an intercellular defense mechanism in the event that tight junctions are breached by acid. It is tempting to speculate that a deficiency of gastric phospholipids may predispose dogs to ulcers. Further, exogenous administration of phospholipids may be useful in preventing gastric ulceration.

Gastric Helicobacter Infection in Dogs

Infection with gastric Helicobacter spp. is prevalent in dogs and is not accompanied by clinical signs in the majority of cases. Five different Helicobacter spp. have been found in the canine stomach. The modes of transmission are unclear, but fecal-oral, oral-oral, and surface water transmission are all possible. A diagnosis can be made using invasive or biopsy-based tests, but noninvasive techniques using UBBT and serology hold promise for the future.

Regulation of apoptotic cell death in the pyloric glands of the canine stomach.

In gastrointestinal epithelia, apoptosis has been thought to play a part in the shedding of postmitotic cells into the lumen. However, we have found that apoptosis more frequently in the generative cell (G) zone (the lower one third of the pit) than in the luminal zone (the upper one third of the pit) and the gland zone in the canine pyloric gland. To analyse the regulation of apoptotic cell death in each zone, we labelled S-phase cells by single and repeated injections of bromodeoxyuridine (BrdU) i.v. at intervals of 8 h. We found that 30% of apoptoses in the G zone were flash-labelled by BrdU and might derive from cells in or just after the S phase. The incidence of apoptosis and mitotic index did not change significantly after repeated injections of BrdU until the 49-h point, when the incidence of apoptosis increased and the mitotic index decreased significantly in the G zone, while the incidence of apoptosis decreased in the luminal zone. The BrdU-induced increase of apoptosis and cell-cycle arrest at the 49-h point may be caused by enhanced DNA mispairs that are elicited by incorporation of BrdU, in particular using the template of BrdU incorporated DNA. Apoptosis in the luminal zone may be down-regulated by reduced cell production in the G-zone.

Effect of nitric oxide in gastric relaxation of canine proximal stomach

Effect of nitric oxide in gastric relaxation of canine proximal stomach

Enhanced motility of the vagotomized canine stomach by electrical stimulation.

Functional impairment of the vagotomized stomach used as a substitute oesophagus seriously deteriorates the quality of life of patients following oesophageal cancer surgery. We speculated that if the enteric neurons of the reconstructed gastric tube survived functionally, the motility of the gastric tube could be facilitated and the recovery process after operation would improve as a consequence. In the present study we investigated whether direct electrical stimulation was effective for facilitating the motility of the canine vagotomized stomach. Dogs underwent truncal vagotomy by transabdominal approach and, in some cases, arteries to the upper stomach and the oesophagus were also ligated and resected to resemble the blood supply and surgical invasion of the reconstructed gastric tube. Electrical stimulation, a few minutes of positive rectangular current pulses, amplitude 20 V (or 15 mA), duration 0.5 ms and frequency between 0.2 and 7 Hz, was delivered on the greater curvature of the mid corpus. Changes in mechanical contractions were recorded using strain gauge force transducers. Electrical stimulation successfully enhanced the mechanical force of the phasic ring contractions of the vagotomized stomach in a frequency dependent manner. Aboral propagation and periodicity of the contractions, impaired by surgical procedures, were restored during stimulation. These excitatory effects were inhibited by atropine, hexamethonium and tetrodotoxin, suggesting that electrical stimulation acts on intramural cholinergic nerves that have survived functionally. These results suggest that electrical stimulation could be an effective method for improving the motility of the vagotomized stomach.

Nitric oxide attenuates endothelin-1-induced vasoconstriction in canine stomach.

We previously observed that endothelin-1 (ET-1)-induced gastric vasoconstriction is enhanced after ischemia-reperfusion. The purpose of our present study was to examine the role of nitric oxide in regulating ET-1-induced vasoconstriction under normal conditions and after ischemia-reperfusion. Using a mechanically perfused stomach segment from chloralose-anesthetized dogs, we examined 1) responses to NG-nitro-L-arginine methyl ester (L-NAME) alone and in combination with L-arginine, 2) whether L-NAME affects ET-1-induced vasoconstriction under normal conditions and after ischemia-reperfusion, and 3) if spermine NONOate {1,3-propanediamine-N-[4-1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazi no] butyl; a nitric oxide donor} attenuates the augmented response to ET-1 after ischemia-reperfusion. Our results show that 1) L-NAME significantly increased baseline vascular resistance and this response was reduced by L-arginine, 2) ET-1-induced vasoconstriction was enhanced by L-NAME, and 3) administration of spermine NONOate during reperfusion largely attenuated the vasoconstrictor response to ET-1 after ischemia-reperfusion. Our findings are consistent with the hypothesis that nitric oxide modulates responses to ET-1 under normal conditions, and loss of this vasodilator after ischemia-reperfusion results in an augmented response to ET-1.

The role of gastric histamine release in the acid secretory response to pentagastrin and methacholine in the dog

We have previously demonstrated that both pentagastrin and methacholine can stimulate histamine release from the canine stomach during short term administration of the secretagogues into the gastrosplenic artery. In this study we tested the hypothesis that gastric histamine release determines the acid secretory response to acid secretagogues. Increasing doses of pentagastrin (2, 6, and 20 ng/kg/min) and methacholine (0.1, 0.3, and 1 micrograms/min) were infused into the gastrosplenic artery in dogs, while gastric acid output, histamine and N tau-methyl histamine secretory rates were monitored. Histamine and N tau-methyl histamine concentrations in plasma were measured using GC/NICI-MS. Increasing doses of pentagastrin resulted in increasing gastric output. Total histamine secretory rate expressed as the sum of histamine and N tau-methyl histamine secretory rate showed a significant increase above basal with the two highest doses of pentagastrin. Regression analysis correlating the dose of pentagastrin to gastric acid output gave a correlation coefficient of 0.586 which was very significant. Regression analysis correlating the total histamine secretory rate to acid output gave a correlation coefficient of 0.498 which was also very significant. Increasing doses of methacholine also resulted in a dose-dependent increase in acid output. Histamine secretory rates showed a statistically significant increase above basal only at the 1 microgram/min infusion rate, however, the total histamine secretory rates (histamine + N tau-methyl histamine) were no longer significant at any of the doses of methacholine.(ABSTRACT TRUNCATED AT 250 WORDS)

An experimental model of gastric pacing in the canine stomach

An experimental model of gastric pacing in the canine stomach

Loss of circadian rhythm in luminal acidity of canine stomach by implantation of a gastric fistula.

One to four months after implantation of a gastric fistula, a circadian rhythm in gastric acidity could be demonstrated by use of the intragastric 24-hour pH-metry in dogs with the gastric fistula protruding on the left side of the upper abdomen. This circadian rhythm was found to be fully developed within 3 years, and it remained unchanged up to 5 years after implantation. It is characterized by a daytime intragastric median pH of about 2 and a nocturnal intragastric median pH of about 7. In contrast, a circadian rhythm did not develop within 5 months after instrumentation of the dogs with a gastric fistula protruding on the right side of the upper abdomen. Only 2 years after implantation of the fistula, an intragastric daytime median pH of about 2 and a nocturnal median pH of about 4 appeared. Four years after implantation, the circadian rhythm had evolved. The results show a delayed postoperative restoration of circadian rhythm in canine gastric acidity if a gastropexy occurs at an untolerated position. This may lead to unphysiological distensions in the gastric wall with subsequent continuous stimulation of acid secretion.

Acute Ulcers Induced in Canine Stomachs by Endoscopic Compressed Air Delivery of 25 mg NaCl

Abstract: Endoscopic administration of 25 mg NaCl powder to target sites on the gastric mucosa of five dogs, using a compressed air delivery system developed by the author, was followed by observation of changes in the gastric mucosa. After 30 seconds, 1 minute, 2 minutes, 5 minutes and 10 minutes, the sprayed NaCl was washed away by endoscopic water spray, and the presence of submucosal bleeding was observed at the target sites. After 24 hours, ulcers in the gastric mucosa were recognized at sites at which the NaCl had been in contact for 2 minutes or more before being washed away. With one minute or less contact time between NaCl and the mucosa, erosion and redness were observed at the target sites. In a control study, however, no mucosal lesions occurred following identical spray of 25 mg lactose powder which was left in contact for 30 seconds, 1 minute, 2 minutes, 5 minutes and 10 minutes, and also 24 hours.Experimental gastric ulcers can be induced by endoscopic administration of a small amount of NaCl powder. The time of contact of NaCl on the gastric mucosa affected the induction of gastric mucosal damage. This method will be useful in the investigation of the direct effects of various drugs on the gastric mucosa.

Vagovagal inhibition of motilin-induced phase III contractions by antral acidification in dog stomach

Gastric acidification at pH 1.0 strongly inhibits the spontaneously occurring and motilin-induced phase III contractions in canine and human stomach. In this study, we examined inhibition by gastric acidification in dogs following gastrojejunostomy, truncal vagotomy, and antrectomy. As a result, gastric acidification with 0.1 N HCl solution at pH 1.0 for 30 min at a rate of 1.0 ml/min significantly inhibited motilin-induced phase III activity to 23.5 +/- 5.9% of the control in the normal intact dogs and to 17.2 +/- 3.4% in the gastrojejunostomized dogs. In the antrectomized dogs, gastric acidification did not significantly inhibit the action of motilin (81.7 +/- 10%), but, in the vagotomized dogs, gastric acidification inhibited the action of motilin to 72.0 +/- 4.9%; the inhibition was much weaker than in the intact and gastrojejunostomized dogs but was significant. The duodenal acidification had no effect at all on the action of motilin (94.6 +/- 12.5%) in the gastrojejunostomized dogs. These findings strongly suggest the existence of a vagovagal reflex in the inhibition of motilin-induced phase III contractions by gastric antral acidification, although the involvement of sympathetic regulation cannot be completely ruled out.

Inhibition of phase III activity by acid in canine stomach

Very few phase III activity of the interdigestive migrating contractions (phase III) occurs in the stomach of fasted duodenal ulcer patients. But the mechanism is not well understood. In this study, we studied the effect of gastric and duodenal acidification on the spontaneous phase III activity in the upper gastrointestinal tract of conscious dogs. Gastric and duodenal motor activity in 5 conscious dogs was monitored by means of chronically implanted force transducers. Intragastric pH changes were measured by placing a pH glass electrode in the gastric antrum. Intragastric and intraduodenal acidification was achieved by i.v. infusion of histamine, and by intragastric and intraduodenal instillation of acidic solutions of different pHs. The plasma motilin concentrations were measured by radioimmunoassay. Histamine (40 μg/kg/h) inhibited spontaneous phase III activity, but the histamine-induced inhibition was completely prevented by pretreatment with famotidine, a potent histamine H 2 receptor antagonist (0.3 mg/kg, i.v.). Intragastric acidification at pH 1.0 strongly inhibited spontaneous phase III activity, but an acidic solution at pH 2.0 had no effect in inhibiting phase III activity. Intraduodenal acidification at pH 1.0 also inhibited spontaneous phase III activity. Histamine injection and gastric and duodenal acidification at pH 1.0 strongly suppressed motilin release. It is concluded that gastric and duodenal acidification at pH 1.0 inhibits the occurrence of the spontaneous phase III activity, and the suppression of endogenous release of motilin due to gastric and duodenal acidification at pH 1.0 is involved in this inhibitory mechanism.

THE FUTURE OF INTESTINAL PACING

Pacing the human heart, first done in 1952, is commonly used today. Pacing the canine stomach and small intestine has also been accomplished and has been used to treat a variety of disease models, including dumping, the short bowel syndrome, gastroparesis, the Roux stasis syndrome, and tachygastria. In contrast, pacing the human stomach and small intestine has not progressed as far. Pacing of these organs in man has only been done for short intervals. Moreover, no clear-cut therapeutic applications have as yet emerged. Nonetheless, pacing holds promise as a future therapeutic modality for a variety of disorders of the human stomach and small bowel.

Effect of region, temperature and neuronal blockade on sodium and 51Cr-EDTA transport across canine gastrointestinal mucosae in vitro

Muscle-stripped segments of canine stomach, ileum and colon have been used to identify regional differences in the movement of sodium and 51 Cr-EDTA, and the effect that temperature has on the flux of these probes. Flux measurements revealed that the rate of movement of both probes followed the pattern ileum > colon > stomach. Analysis of flux ratios at 25°C and 37°C revealed that sodium moves actively and 51Cr-EDTA moves passively across gastrointestinal epithelia. Blockade of tonic neuronal activity did not affect the in vitro movement of either probe across the ileum.

Gastroprokinetic properties of the benzimidazolone derivative BIMU 1, an agonist at 5-hydroxytryptamine4 and antagonist at 5-hydroxytryptamine3 receptors

We have investigated the in vivo motor stimulating and gastroprokinetic properties of the azabicycloalkyl benzimidazolone derivative BIMU 1 (3-ethyl-2,3-dihydro-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2-oxo-1H- benzimidazole-1-carboxamide hydrochloride) and its binding profile at 5-hydroxytryptamine3 and 5-hydroxytryptamine4 receptors, in an attempt to assess the serotonergic mechanism underlying its prokinetic action. BIMU 1 dose-dependently (0.01-0.3 mg/kg i.v.) increased the motility of a denervated pouch of canine stomach. This excitatory action was sensitive to muscarinic blockade. A similar stimulatory effect was exerted by the benzamidic prokinetic agent cisapride (0.03-0.3 mg/kg i.v.) but not by the 5-HT3 receptor antagonist ondansetron (up to 1 mg/kg i.v.). The significance for propulsive efficacy of the motor stimulating activity of BIMU 1 was evaluated in a model of gastric emptying of liquids in the conscious dog. The emptying rate of a non-caloric liquid meal instilled through a gastric fistula was accelerated by both BIMU 1 (0.01-1 mg/kg i.v. and 0.1-3 mg/kg p.o.) and cisapride (0.03-1 mg/kg i.v. and 0.3-10 mg/kg p.o.). Ondansetron (1 mg/kg i.v.) did not show any effect. The activity of the 5-HT4 receptor antagonist DAU 6285 was evaluated in the gastric emptying model per se and in interaction experiments on the accelerating action of BIMU 1 (0.3 mg/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)

薬物性胃粘膜障害の新たな評価法 （ＩＩ） 乳糖混合による薬物胃粘膜直接障害の抑制

25 mg powder of NaCl or asprin mixed 25 mg of lactose was administered to the target on gastric mucosa by air flow carrying system through endoscope. NaCl or aspirin produced gastric ulcer, but, the mixture of lactose produced redness and/or erosions on target sites after 24 hour. The direct gastric mucosal injury of drug can be reduced the mixing of lactose.When powder of sucralfate mixed with NaCl or asprin was administered to gastric mucosa, redness and/or erosions lesions observed after 24 hour at target sites. Similarly, benexate hydrochloride β-cyclodextrin clathrate mixing NaCl or aspirin, produced redness and/or erosions lesions in canine stomach. The direct gastric mucosal injury can be reduced the mixing of sucralfate and/or benexate hydrochloride β-cyclodextrin clathrate which have direct effect to gastric lesions.