Blood flow distribution in the stomach of cats with acute gastric ulcer

An ulcer was induced in the anterior wall of the antrum of cats by local injection of acetic acid solution. Carbonized microspheres, 15 +/- 5 microns in diameter, labelled with 141Ce, were used to measure blood flow in different regions and layers of the stomach wall. The radioactivity of a blod reference sample and of tissue samples was determined, and the blood flow was calculated for each tissue sample. The gastric tissue samples were examined microscopically, and the level of gastrin in serum was determined. Two groups of anaesthetized animals were used: in one group of animals blood flow was determined 24 h after ulcer induction and in a group of control animals 24 h after laparotomy. In the ulcer animals the gastric blood flow as increased both in the mucosa and in the muscularis in a zone around the ulcer. Microscopic examination revealed tissue necrosis corresponding to the floor of the ulcer and acute inflammatory changes in the gastric wall around the necrotic area. The serum gastrin concentration tended to increase after ulcer induction.     

Effect of indomethacin on blood flow distribution in the stomach of cats with acute gastric ulcer

An ulcer was induced in the anterior wall of the antrum of cats by local injection of acetic acid solution. Carbonized microspheres, 15 +/- microns in diameter, labelled with 141Ce, 46Sc, and 85Sr, were used to measure blood flow in different regions and layers of the stomach wall. The radioactivity of a blood reference sample and of tissue samples was determined, and the blood flow was calculated for each tissue sample. The blood flow distribution was determined before, 1/2 h, and 1 h after an intravenous infusion of indomethacin in a dose of 3 mg/kg. Two groups of anaesthetized animals were used: animals with a 24-h gastric ulcer and control animals 24 h after laparotomy. In the control animals indomethacin caused a mean reduction in gastric mucosal blood flow of approximately 50%. The flow reduction was about the same in different regions of the stomach. In the muscularis there was no change in blood flow after indomethacin. The blood flow was reduced in the duodenum and jejunum but not in the other intestinal organs studied. The blood pressure and cardiac output remained unchanged. In the ulcer group indomethacin caused about the same reduction in mucosal blood flow. However, the blood flow was reduced less in the ulcer region and tended to increase in the mucosa around the ulcer 1 h after indomethacin infusion.     

A controlled study of human resting gastric mucosal blood flow by endoscopic laser-Doppler flowmetry

We investigated regional variation in resting focal gastric mucosal blood flow obtained by endoscopic laser-Doppler flowmetry in patients with symptoms of dyspepsia or peptic ulcer (N = 12) and asymptomatic healthy volunteers (N = 6). Mucosal blood flow was measured for 1 min at the duodenum (first part), prepylorus, antrum and body (anterior and posterior walls), angularis, mid-greater curvature, fundus, and distal esophagus. At all sites, mean +/- SE blood flow in patients was 71.88% of the corresponding value in volunteers (1.15 +/- 0.10 and 1.60 +/- 0.13 volts, p less than 0.02, t test). In both groups, blood flow was highest in the fundus, followed by the body and lowest in the antrum; the angularis had a high blood flow, second only to the fundus. There was no correlation between age and blood flow. We conclude that regional variation in resting gastric mucosal blood flow exists in health and disease.     

Effect of hemorrhagic shock on oxidative phosphorylation and blood flow in rabbit gastrointestinal mucosa

The pathophysiologic mechanism responsible for ulceration of gastric fundus and corpus mucosa following hemorrhagic shock is not well defined. We examined the effect of hemorrhagic shock (25 ml blood/kg) and resuscitation (reinfusion of shed blood) on oxidative phosphorylation in different tissues of the rabbit to determine if differences in mitochondrial response to hemorrhagic shock and resuscitation contribute to the propensity of gastric fundus and corpus to necrose before other tissues. Blood flow was measured by using radioisotope-labeled microspheres to determine if changes in regional blood flow could be correlated with this propensity to ulcerate. The respiratory control index (RCI), an index of the integrity of mitochondrial function, was significantly increased in gastric antrum, liver, and kidney from the animals subjected to hemorrhagic shock and successful resuscitation when compared to control animals. In liver and kidney, these differences were largely due to increases in state 3 respirations. Duodenal and gastric corpus and fundus mitochondria showed no differences in RCI between bled and control groups. Blood flow data did not implicate ischemia as the mechanism responsible for the differential rate of ulceration after hemorrhage. The inability of fundus, corpus, and small-bowel mucosal mitochondria to respond to the stress of hemorrhagic shock and resuscitation in a manner similar to liver, kidney, and gastric antral mitochondria may place these tissues at greater risk to ulcerate. Further work is necessary to define whether this difference in mitochondrial response patterns represents a real increase in the maximal respiratory capacity of liver, kidney, and antrum after shock and resuscitation.     

A new model of stress ulcer in the rat with pylorus ligation and its pathogenesis

Water-immersion stress for 7, 14, or 20 hr consistently induced linear or punctate stress ulcers (mucosal erosions) in the corpus of the stomach in intact rats. When the pylorus of the stomach had been ligated prior to stressing, the stress ulcers changed their morphological feature (mainly punctate and in one place elongated) and location (both in corpus and antrum). Histologically, the stress ulcer developed in the proximal antrum of pylorusligated rats and penetrated into the muscularis mucosa. Sodium bicarbonate, chlorpromazine, hexamethonium, atropine, metiamide, and bilateral vagotomy markedly inhibited the stress ulcers which developed in the pylorus-ligated rats. Phentolamine and propranolol hardly affected the development of stress ulcers. Amylopectine evoked a new type of stress ulcer in the corpus when it was given to the pylorus-ligated rats.     

Locations of peptic ulcers in children

The locations of peptic ulcers in children were studied in a total of 55 cases; 19 with gastric ulcers, 31 with duodenal ulcers and 5 with a combination of both. The male children were predominantly affected with these three types. The mean age of the children with gastric ulcers was significantly lower than those with duodenal ulcers (P<0.005). Gastric ulcer was markedly predominant in the antrum, and commonly present in the anterior and posterior walls of the stomach, and infrequently on the greater curvature. Ten of 24 cases (42%) had ulcerations on the anterior wall of the antrum. In seven cases, ulcerations were located on the posterior wall. Duodenal ulcers mostly occurred in the bulb. The anterior and/or posterior walls of the bulb were commonly associated with ulcerations. The present observations concerning gastric and duodenal ulcer location are essentially in agreement with results from adult studies. Perforations were demonstrated in the anterior wall or lesser curvature in both gastric and duodenal ulcers. In five of seven replapse cases, ulcerations had recurred in the same area.     

Locations of peptic ulcers in children

The locations of peptic ulcers in children were studied in a total of 55 cases; 19 with gastric ulcers, 31 with duodenal ulcers and 5 with a combination of both. The male children were predominantly affected with these three types. The mean age of the children with gastric ulcers was significantly lower than those with duodenal ulcers (P less than 0.005). Gastric ulcer was markedly predominant in the antrum, and commonly present in the anterior and posterior walls of the stomach, and infrequently on the greater curvature. Ten of 24 cases (42%) had ulcerations on the anterior wall of the antrum. In seven cases, ulcerations were located on the posterior wall. Duodenal ulcers mostly occurred in the bulb. The anterior and/or posterior walls of the bulb were commonly associated with ulcerations. The present observations concerning gastric and duodenal ulcer location are essentially in agreement with results from adult studies. Perforations were demonstrated in the anterior wall or lesser curvature in both gastric and duodenal ulcers. In five of seven relapse cases, ulcerations had recurred in the same area.     

Intramural distribution of regulatory peptides in the human stomach and duodenum

The distribution of regulatory peptides was studied by radioimmunoassay in the separated mucosa, submucosa and muscularis externa of the human oxyntic stomach, antrum and duodenum. Immunoreactive gastrin, secretin, gastric inhibitory polypeptide and motilin were virtually confined to the mucosa and duodenal submucosa, where endocrine cells are present. Only minor amounts of motilin and gastrin (3.2 +/- 0.5% and 4.3 +/- 0.8% of their total content, means + SEM, respectively) were found in the separated duodenal muscle. Somatostatin-, vasoactive intestinal polypeptide-, substance P-, and mammalian bombesin-like peptides showed distinct differential distributions in all layers. Substance P was low in the stomach and markedly increased in the duodenum, especially in the mucosa (fundus 0.8 +/- 0.2 pmol/g, duodenum 66 +/- 12). Vasoactive intestinal polypeptide and somatostatin, although well represented in the stomach, also increased in the duodenum in all layers of the wall (whole fundus 281 +/- 33 and 334 +/- 46 pmol/g, antrum 124 +/- 18 and 426 +/- 59, duodenum 507 +/- 99 and 1816 +/- 149, respectively). Mammalian bombesin immunoreactivity was comparatively abundant in the oxyntic stomach (mucosa 34 +/- 4.5 pmol/g, muscularis externa 29 +/- 4.8), less so in the antrum (6.3 +/- 1.5 and 11 +/- 3.2 pmol/g, respectively). Low concentrations of this peptide were measured in the duodenum, practically confined to the muscle (this layer 5.1 +/- 1.5 pmol/g, or 83 +/- 5.6% of the total content).     

胃镜诊断35例胃憩室特点分析

目的探讨胃憩室胃镜下表现和特点。方法回顾分析35例经胃镜确诊的胃憩室患者胃镜下表现。结果胃镜检查确诊胃憩室35例,检出率0.058%。男女性别构成差异无统计学意义（P〉0.05）。憩室位于胃底和胃窦者分别占48.57%和42.86%,明显多于8.57%的胃体憩室。胃体憩室直径显著大于胃窦（P〈0.01）,胃体憩室患者年龄也显著大于胃窦憩室患者（P〈0.05）。胃底憩室多见于大弯和后壁,胃窦憩室多见于大弯侧,胃体憩室多见于前、后壁。结论胃憩室是一种罕见病,多见于胃底和胃窦,男女检出率相当,并发症少见。     

Experimental chronic gastric ulcer due to ischemia in rats

Ligation of the left gastric and right gastroepiploic arteries and veins resulted in chronic gastric ulcer formation in the rat. Linear mucosal corpus hemorrhages appeared within 8 hr of ligation. By 2 days large corpus hemorrhagic erosions were present. A single, large ulcer involving nearly the entire corpus was present at 3–5 days. In the ulcerated area the mucosa and muscularis mucosae were destroyed, thick granulation tissue filled the submucosa and the muscularis propria was severely damaged. Progressive healing occurred thereafter and 75% of the ulcers healed completely grossly in 2–8 weeks. Histologic studies showed that healing and mucosal regeneration occurred by the outgrowth of a layer of cells from the adjacent intact epithelium extending over the surface of the ulcer. Invaginations from this covering layer of cells formed a glandular mucosa composed of mucous cells. Later parietal and chief cells appeared, and eventually (6 months) a normal corpus-type mucosa covered the entire corpus. With time smooth-muscle fibers appeared in the outer half of the dense submucosal granulation tissue and eventually a normal muscularis mucosae, submucosa, and muscularis propria were present (6–12 months). These studies show that: (1) ischemia can give rise to chronic gastric ulcer, and (2) all elements of the gastric wall, including the mucosa, the muscularis mucosae, and the muscularis propria can fully regenerate.Supported by Veterans Administration Project Number 3324-02 and NIAMDD Peptic Ulcer Center Grant 17328     

Heterogeneous distribution of gastric mucosal blood flow with restraint stress in the rat

Cold water immersion restraint (CWIR) is associated with gastric hypercontractility and gastric corpus erosions in the rat. Because the gastric blood flow response to CWIR has not been well defined, we performed the following study. Rats were implanted with force transducers, subjected to CWIR for 2 hr, and then blood flow was determined by the iodo[¹⁴C]antipyrine autoradiographic (IAP) technique. When compared to control animals, the CWIR-treated animals displayed foci of gastric corpus hyperemia with a marked and significant increase in blood flow in all layers of the gastric corpus. There was approximately a 100% increase in the mucosa and a 50% increase in the muscularis externa. The hyperemia was not uniform, but rather alternated every 2.1±0.2 mm with regions of low blood flow. Blood flow in the antrum and duodenum was unaffected by CWIR. We conclude that CWIR is associated with alternating regions of high and low blood flow only in the gastric corpus. Reduction of corpus mucosal blood flow might be due to the powerful gastric contractions associated with CWIR.     

Changes of Regional Gastric Flow Measured by Hydrogen Clearance Techniques after Histamine Stimulation in Conscious Animals

Gastric microcirculatory changes were studied by means of hydrogen clearance techniques in conscious cats during histamine stimulation. A considerable increase of corpus mucosa flow occurred, whereas a less substantial increase of antrum mucosa flow was observed during stimulation with histamine at 2 μg/kg/min, intravenously. Stepwise increase of infused histamine was accompanied by a gradual increase of corpus flow in the mucosa, which during supramaximal stimulation decreased slightly but still remained considerably elevated above control values. A similar decrease of antral mucosa flow occurred earlier during maximal stimulation, suggesting shunting of blood from the antrum to the corpus region. Total gastric flow measurements performed in anesthetized animals similarly showed decreased flow at a rate of histamine infusion which produced supramaximal stimulation in the conscious animals. However, total gastric flow remained elevated also during this stage compared with prestimulation values. A hypothesis of a dual effect of histamine on the gastric circulation is suggested, including regulation of flow through generalized vasodilatation and increased metabolic activity in the parietal cell mass.     

Measurement of immunoreactive gastrin in gastric mucosa.

A method for measurement of gastrin in gastric mucosa has been developed, and distribution of gastrin in the stomach of pig, dog, cat, rabbit, and man was examined. Measurable amounts of gastrin were found in corpus of all species, but the content in the antrum was considerably higher. The highest concentration of gastrin was seen in man. The borderline between corpus and antrum was abrupt, and in both parts of the stomach gastrin was evenly distributed. In 44 patients with duodenal ulcer the antral gastrin concentration was 21.3 mug eqv. per g mucosa, in 15 patients with prepyloric ulcer 23.0, in 10 patients with gastric ulcer 5.9, and in 16 patients with gastric carcinoma 7.9. The control group consisted of 10 healthy volunteers and 12 patients with minor abdominal complaints. Mean antral gastrin concentrations were 28.1 and 20.7 respectively. No significant relationship was observed between PAO and gastrin content of antral mucosa in any group.     

Altered Concentrations of Gastrin-Releasing Polypeptide and Somatostatin in Fundic and Duodenal Bulb Mucosa of Patients with Duodenal Ulcer Disease

The concentrations of gastrin-releasing polypeptide, somatostatin (SS), and gastrin in extracts of endoscopically obtained biopsies from the fundus, antrum, and duodenum of patients with uncomplicated bile stones (controls) or duodenal ulcer disease were measured with specific radioimmunoassays. The validity of the tissue sampling was confirmed by characteristic and significant differences between gastrin concentrations at the different biopsy sites. Gastrin-releasing polypeptide levels were at their highest in the fundic and duodenal bulb compared to the antrum in controls (p less than 0.01), whereas no differences in gastrin-releasing polypeptide content of the different parts of the stomach were found in duodenal ulcer patients. Compared to controls gastrin-releasing polypeptide in duodenal ulcer patients was reduced in fundic and duodenal bulb mucosa (p less than 0.01). SS levels were highest (p less than 0.05) in the first part of duodenum in controls. Compared to controls duodenal ulcer patients had lower SS concentrations present in fundic (p less than 0.01) and highest SS concentrations present in duodenal bulb mucosa (p less than 0.01). There was no correlation between acid secretion and mucosal gastrin-releasing polypeptide or SS concentrations in any part of the stomach and duodenum.     

Effect of cimetidine on augmented gastric blood flow in duodenal ulcer patients.

Blood flow in the human stomach was measured during operation with a 85Krypton washout method which made simultaneous determinations of total blood flow and intramural flow distribution possible. The antrum and the corpus of the stomach could be investigated separately. Eleven patients with duodenal ulcer disease were studied during pentagastrin infusion and after the addition of cimetidine, 3 mg/kg bw, to evaluate the effect of the drug on augmented gastric blood flow. Eight recordings were made over the corpus of the stomach and three recordings over the antrum. Cimetidine caused a 66 +/- 5% decrease (mean +/- SE; range 56-86) in acid secretion and a 62 +/- 5% decrease (range 44-91) in the corpus mucosal blood flow within 15 minutes. Changes were only seen in the acid secreting part of the stomach while the antral circulation remained unaltered. It is concluded that the decrease in pentagastrin induced vasodilatation in the stomach seen after giving cimetidine was secondary to an inhibition of acid secretion.     

Role of endothelin-1 in repeated electrical stimulation-induced microcirculatory disturbance and mucosal damage in rat stomach

The aim of the present study was to clarify the involvement of endogenous endothelin in the pathogenesis of gastric mucosal damage. The rat stomach was exposed and repeated electrical stimulation (RES) was applied to the small arterial wall close to the lesser curvature. Significant mucosal haemorrhagic lesions (ulcer and erosion) were noted within 30 min after RES. Intravital microscopic observations revealed that an arteriolar constriction occurred in the submucosal layer of the rat stomach approximately 5 min after the completion of RES. Following the arteriolar constriction, the mucosal blood flow of the rat stomach, which was monitored by using a laser Doppler velocimeter, decreased to approximately 30% of the control value. The plasma immunoreactive endothelin-1 level in the regional blood of the stomach was significantly increased immediately after RES preceding the decrease in mucosal blood flow. Immunohistochemical studies revealed that endothelin-1 and big-endothelin-1 were detectable in the arteriolar endothelium around the muscularis mucosa, supporting the involvement of endothelin-1 in RES-induced mucosal ischaemia. In addition, BQ-123, a specific antagonist of the endothelin A (ET_A) receptor, attenuated the reduction of blood flow and the development of haemorrhagic lesions observed in gastric mucosa subjected to RES. The results of the present study suggest that an excessive production of endothelin-1 in the arteriolar endothelium leads to microvascular derangements accompanied by haemorrhagic alterations of the gastric mucosa.     

Plasma and Gastric Mucosal Endothelin-1 Concentrations in Patients with Peptic Ulcer

Peptic ulcer in the human stomach causeslocalized destruction of the gastric wall, which may beassociated with focal vascular insufficiency.Endothelin-1, an extremely potent vasoconstrictorpeptide, modulates regional blood flow in thevasculature of stomach, suggesting a role forendothelin-1 in peptic ulcer. We examined therelationship among endogenous plasma and mucosalendothelin-1 concentrations and the severity and area of ulcer in 19patients with gastric ulcers and eight healthy adults.Endothelin-1 concentrations were measured by enzymeimmunoassay in plasma and gastric mucosal specimens from ulcer margins, corpus, and antrum. The severityand area of ulcer were assessed endoscopically. Plasmaendothelin-1 concentrations in active (P < 0.01compared with normal) and healing (P < 0.05) stagesof ulcer were significantly greater than those innormal subjects. Plasma endothelin-1 concentrations, butnot mucosal endothelin-1 concentrations in the ulcermargin, were significantly associated with the severity of the ulcer. There was a significantpositive correlation between plasma endothelin-1concentration and area of ulcer (r = 0.70, P < 0.01).In conclusion, locally increased endothelin-1 may be an important mediator contributing to thepathogenesis of peptic ulcer.     

Effect of decreased blood flow and ischemia on myocardial thallium clearance

To determine the effect of reduced coronary blood flow on myocardial thallium-201 clearance over a range of flows, miniature radiation detectors were inserted into the left ventricular apex and positioned against the anterior and posterior endocardial walls in 21 dogs. Thallium was administered intravenously and myocardial tracer activity was monitored continuously for 1 hour in both walls. A balloon occluder was then partially inflated around the left anterior descending coronary artery in 19 dogs, producing a range of anterior wall blood flow reductions as assessed by the microsphere technique. Thallium activity was monitored continuously for 3 hours in both walls. Two dogs served as control animals and had no coronary artery occlusion at 1 hour. At the end of the 4 hour experiment, the dogs were sacrificed and the hearts counted in a well counter. The 19 dogs with coronary artery stenosis were divided into three groups (mild, moderate and severe flow reduction groups) on the basis of their poststenosis anterior/posterior wall regional myocardial blood flow ratios. The two control dogs had similar thallium clearances in the anterior and posterior left ventricular walls during the 3 hour period, as assessed by the radiation detectors, and by a final anterior/posterior wall thallium ratio near unity. All three groups of dogs with coronary stenosis had comparable fractional thallium clearances from the anterior and posterior walls before and after the balloon occluder inflation. The final anterior/posterior left ventricular wall thallium ratios were not significantly different than unity for all three groups of dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Persistent oxidative stress in the corpus mucosa is evoked by long-term treatment of H. pylori-infected patients with proton pump inhibitors

BACKGROUND/AIMS: To examine the influence of long-term treatment of H. pylori-infected patients with proton pump inhibitors (PPI) on the toxic oxidant production in the stomach. METHODOLOGY: Eight H. pylori-positive patients with gastric ulcer were enrolled, and tissue samples were obtained endoscopically from the antrum and corpus. The tissue contents of neutrophil myeloperoxidase (MPO) and oxygen-derived free radicals were quantified by ELISA and chemiluminescence (ChL) assay. The H. pylori density in the tissue specimens was scored by immunohistochemistry and the mucosal infiltration by neutrophils and monocytes was scored by histopathology. The effects of PPI on these parameters were evaluated by oral administration of lansoprazole (LPZ) at the dose of 30mg od for 8 weeks, followed by 15mg for 24 weeks. RESULTS: Eight-week treatment with LPZ significantly increased the corpus ChL by 400%, which remained unchanged at this level during the subsequent 24 weeks, but the antrum ChL decreased slightly following LPZ-treatment. No significant changes in the mucosal MPO activity or the histologically determined parameters of H. pylori density and neutrophil/monocyte infiltration were observed in either portion of the stomach. CONCLUSIONS: The mucosal oxidative stress level significantly increased in the corpus mucosa after long-term treatment with LPZ, which may be independent of inflammatory cell infiltration.     

Temporal Patterns of Colonic Blood Flow and Tissue Damage in an Animal Model of Colitis

This study tested the hypothesis that alteredcolonic blood flow may contribute to tissue damageduring the development of colitis in the rabbit. Thiswas achieved by using radioactive microspheres tomeasure colonic blood flow at various times aftercolitis induction with trinitrobenzene sulfonic acid.Significant colonic damage occurred 6 hours post colitisinduction and persisted throughout the 5 day study. Blood flow to the muscularis propria andmucosa/muscularis mucosae compartments increasedsignificantly from 5 minutes until one hour postinduction. At 6 and 12 hours post induction colonicblood flow returned to control levels before increasingagain from 24 to 96 hours. This second increase in flowwas, however, predominantly in the mucosa/muscularismucosae compartment. Blood flow in the stomach and non-gastrointestinal tissues did not changesignificantly at any time. These data demonstrate thatincreased colonic blood flow may be disrupted in theearly stages of colitis and that this coincides with the onset of significant damage. It isconcluded that maintenance of elevated colonic bloodflow throughout the development of colitis may help toameliorate subsequent tissue injury.