Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of endogenous acid was evaluated in a rat model of gastric epithelial damage induced by local ischemia-reperfusion (IR). Because no gross lesion was induced in this model, the damage was quantified by measuring the blood-to-lumen [51Cr]EDTA clearance. A proton pump inhibitor (omeprazole) or an H2-receptor antagonist (T-593) was used to suppress luminal acidity from pH 5 to pH 6.3-7.0. Both drugs significantly attenuated the increase in clearance induced by IR, indicating an important role for endogenous acid. A second series of experiments was performed to confirm whether the change in pH from around 5 to 7 was sufficient to reduce IR-induced gastric mucosal damage. Phosphate-buffered saline was perfused into the gastric lumen to neutralize the endogenous luminal acid. Although the luminal acid was completely neutralized, no reduction in clearance was observed. These data indicate that endogenous luminal acid does not play an important role in gastric injury induced by local IR stress and that a proton pump inhibitor or H2-receptor antagonist may suppress IR injury by a mechanism other than reducing luminal acidity, i.e., reducing consumption of ATP needed for acid secretion, thereby improving gastric mucosal energy metabolism.
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PMID:Role of endogenous acid in gastric mucosal injury induced by local ischemia-reperfusion in the rat. 877 1

A new model of gastric ulcer involving damage to the muscularis mucosae was developed by clamping the celiac artery in rat to induce ischemia-reperfusion (I-R) injury. Although erosions with falling off of the gastric mucosa were observed immediately, 24 and 36 hours after the I-R, gastric ulcers involving the injury of muscularis mucosae were observed in the area of gastric glands at 48 and 72 hours after initiation of injury. Administration of omeprazol, a proton pump inhibitor, or pentoxifylline, an anti-leukocyte drug, just after the initiation of injury significantly decreased the total area of ulcers at 72 hours. A combination of omeprazol and pentoxifylline was more effective than either drug alone. An anti-leukocyte adhesion molecule (anti-CD18 antibody) also showed significant inhibitory effect on the development of ulcers at 72 hours and the infiltration of leukocytes into both submucosa and mucosa. These results indicate that in our model, gastric acid together with leukocytes contribute to the development of ulcers following erosions. This model may be used to investigate the mechanisms of the development of gastric ulcer and evaluate antiulcer drugs in a preclinical setting.
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PMID:A new gastric ulcer model induced by ischemia-reperfusion in the rat: role of leukocytes on ulceration in rat stomach. 891 34

Gastrointestinal involvement occurs in most patients with systemic sclerosis and is subclinical in about one third. Early pathology is characterized by vasculopathy, resulting in tissue ischemia and progressive dysfunction. Noninvasive esophageal studies using semisolid bolus scintigraphy are sensitive but lack specificity. Long-term treatment of reflux with high-dose proton pump inhibitors appears safe and effective for symptom relief and may prevent recurrence of esophagitis and stricture. Dyspepsia may result from gastroparesis and antral distension. Gastric antral vascular ectasia is a vascular manifestation, and bleeding may be controlled endoscopically. Prokinetic agents effective in pseudoobstruction include metoclopramide, domperidone, cisapride, octreotide, and erythromycin. Patients with intestinal neuropathy or response to bolus octreotide are more probable long-term responders. The combination of octreotide and erythromycin may be particularly effective in systemic sclerosis. The combination of cisapride and erythromycin may cause serious cardiac arrhythmia and is contraindicated. Omeprazole may predispose to small intestinal bacterial overgrowth. Malabsorption not responding to antibiotic therapy should be investigated with small-bowel biopsy to rule out more unusual causes. Pneumatosis cystoides intestinalis may be due to excessive hydrogen production by intestinal bacteria altering the partial pressure of nitrogen in the intestinal wall. In selected cases, surgery for intestinal failure is an option with resection or bypass of affected segments or placement of enterostomy tubes for feeding or decompression. Careful preoperative characterization of intestinal segments is required.
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PMID:Gastrointestinal features of scleroderma. 901 61

Although most patients with gastroesophageal reflux disease (GERD) present with the classic symptoms of heartburn and acid regurgitation, many complain of atypical chest pain suggestive of cardiac disease. Once cardiac ischemia has been excluded, it is important to consider GERD because this may be established as the cause of pain in 10% to 50% of such patients. If GERD is suspected or documented, vigorous antireflux treatment, preferably with proton pump inhibitory therapy, is indicated.
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PMID:Management of complicated gastroesophageal reflux disease: atypical chest pain. 934 86

Ischemia followed by reperfusion is known to produce gastric lesions due to oxidative stress, but the role of gastric H(+) secretion in the formation of this mucosal injury remains unknown. We studied alterations in gastric acid secretion and gastric histamine content, as well as the expression of histidine-decarboxylase and interleukin-1beta during the mucosal recovery from ischemia-reperfusion erosions. Gastric secretion was studied in rats (series A) with gastric fistula before, during and after the ischemia induced by clamping of celiac artery for 0.5 h followed by reperfusion in animals pretreated with vehicle (saline), omeprazole, a proton pump inhibitor, or ranitidine, a histamine (H(2)) receptor antagonist. In series B, the animals were submitted to 0.5 h of ischemia followed by 1 h of reperfusion and then anesthetized at 0, 3, 12 and 24 h or 3, 5, 10 or 15 days after the end of ischemia-reperfusion to determine gastric blood flow by H(2)-gas clearance technique, area of gastric lesions, plasma gastrin and interleukin-1beta levels, histamine content by radioimmunoassay (RIA) and expression of histidine-decarboxylase and interleukin-1beta mRNA by reverse transcription polymerase chain reaction. Clamping of celiac artery caused cessation of gastric blood flow and almost complete suppression of basal gastric acid secretion (series A) that returned gradually to the control value at day 3 after ischemia-reperfusion, accompanied by the rise in plasma gastrin levels, pronounced expression of histidine-decarboxylase mRNA and increased mucosal histamine content. Ischemia, followed by 1 h of reperfusion, produced gastric erosions (series B) that reached maximum at 12 h, but then declined at 24 h. These erosions progressed at day 3 into deeper ulcers whose area declined progressively within the next 5-15 days. The gastric blood ceased to flow (series B) during 30 min of clamping and was reduced throughout the period of healing of acute erosions, being accompanied by a gradual rise in mucosal interleukin-1beta mRNA content and in plasma interleukin-1beta levels. Treatment with omeprazole or ranitidine, which completely suppressed gastric acid secretion and significantly raised plasma gastrin level, greatly reduced the formation of erosive lesions preventing the progression of these lesions to chronic gastric ulcers, and this was accompanied by the rise in gastric blood flow and plasma gastrin levels and the significant attenuation of plasma interleukin-1beta levels. The ranitidine and omeprazole-induced suppression of ischemia-reperfusion erosions were abolished by the instillation of exogenous 0.2 N HCl into the stomach of these rats. The histidine-decarboxylase was faintly expressed in the intact gastric mucosa, but strongly upregulated during mucosal recovery from the damage induced by ischemia-reperfusion. We conclude that following ischemia-reperfusion: (1) gastric acid secretion, gastric microcirculation and histamine production markedly decline, while interleukin-1beta release significantly increases, probably playing an important role in the progression of acute lesions into chronic gastric ulcerations; (2) the suppression of gastric acid secretion by omeprazole and ranitidine, that induces hypergastrinemia, prevents the progression of gastric erosions into ulcers; and (3) the addition of exogenous acid restores the progression of the acute lesions into gastric ulcers, indicating that gastric acid plays a key role in ulcerogenesis induced by ischemia-reperfusion.
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PMID:Role of gastric acid secretion in progression of acute gastric erosions induced by ischemia-reperfusion into gastric ulcers. 1085 59

Gastric mucosal damage occurs in critically ill patients in intensive care units and develops in the setting of severe physiologic stress. Within 24 hrs of admission to the intensive care unit, 75% to 100% of critically ill patients demonstrate evidence of stress-related mucosal disease. Stress ulcers present a risk of clinically important bleeding, which is associated with alterations in physiology, such as hypotension or tachycardia, or results in anemia or the need for transfusion. Clinically important bleeding occurs in approximately 1% to 4% of critically ill patients. The pathophysiology of stress-related mucosal disease is complex. Major factors responsible for stress ulcer are decreased blood flow, mucosal ischemia, and hypoperfusion and reperfusion injury. Acid-suppressive regimens that elevate the intragastric pH and maintain the pH over time have the potential to prevent stress-related mucosal disease. Intragastric pH studies have demonstrated that, whereas a pH of >4 may be adequate to prevent stress ulceration, a pH of >6 may be necessary to maintain clotting in patients at risk of rebleeding from peptic ulcer. Studies comparing the ability of intravenous administrations of histamine-2-receptor antagonists and proton pump inhibitors to raise and maintain intragastric pH suggest that, although both can raise the pH to >4, proton pump inhibitors are much more likely to maintain this pH. Unlike histamine-2-receptor antagonists, proton pump inhibitors can elevate and maintain the intragastric pH at >6. This is relevant for patients in the intensive care unit at risk for rebleeding from peptic ulcers after hemostasis.
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PMID:Pathophysiology of the upper gastrointestinal tract in the critically ill patient: rationale for the therapeutic benefits of acid suppression. 1207 60

Gastrointestinal involvement occurs in most patients with systemic sclerosis. Pathology is characterized by vasculopathy, resulting in tissue ischemia, progressive dysfunction and fibrosis. In its diffuse and visceral pattern, digestive manifestations may involve most of the intestinal tract and are the most frequent before renal, cardiac and pulmonary involvement. Whatever the visceral extension, about 80% of patients have digestive manifestations including gastroesophageal reflux, abnormalities of intestinal motility leading to chronic intestinal pseudo-obstruction and small bowel bacterial overgrowth and malnutrition. Long-term treatment of reflux with high-dose proton pump inhibitors appears safe and effective for symptom relief and may prevent recurrence of esophagitis and stricture. Prokinetic agents effective in pseudoobstruction include metoclopramide, domperidone, octreotide, and erythromycin.
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PMID:[Digestive manifestations in systemic sclerosis]. 1221 92

Stress-related mucosal disease (SRMD) includes stress-related injury (superficial mucosal damage) and stress ulcers (focal deep mucosal damage). Both types are caused by mucosal ischemia, and both show a propensity for the acid-producing corpus and fundus. Prophylaxis of stress ulcers may reduce major bleeding but, so far, has not been shown to improve survival. The most widely used drugs for stress-related injury are the intravenous histamine H(2)-receptor antagonists. Proton pump inhibitors (PPIs) are the most potent acid-suppressive pharmacologic agents. The available PPIs significantly increase gastric pH for up to 24 hours after one dose. Tolerance does not develop, and adverse effects are few. Preliminary studies have demonstrated a significant reduction in SRMD bleeding for patients receiving PPI prophylaxis. PPIs may become an effective tool for reducing the incidence of SRMD in critically ill patients.
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PMID:Stress-related Mucosal Disease. 1262 72

Sickle cell disease is caused by molecular abnormalities in the formation of hemoglobin, leading to pain crisis from recurrent vascular occlusion by sickled hemoglobin. Impaired flow in the microvasculature can lead to ischemia, tissue infarction and ulceration. Abdominal pain, a common complaint in sickle cell disease, can be due to an uncommon etiology, ischemic duodenal ulceration. This is due to primary mucosal infarction caused by sickling, leading to poor healing of infarcted areas. Prompt endoscopic and/or urgent surgical intervention should be considered, particularly if anticoagulation is an issue, as proton pump inhibitor use is ineffective in healing this type of ulcer.
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PMID:Ischemic duodenal ulcer, an unusual presentation of sickle cell disease. 1839 28

The gastric mucosa maintains structural integrity and function despite continuous exposure to noxious factors, including 0.1 mol/L HCl and pepsin, that are capable of digesting tissue. Under normal conditions, mucosal integrity is maintained by defense mechanisms, which include preepithelial factors (mucus-bicarbonate-phospholipid "barrier"), an epithelial "barrier" (surface epithelial cells connected by tight junctions and generating bicarbonate, mucus, phospholipids, trefoil peptides, prostaglandins (PGs), and heat shock proteins), continuous cell renewal accomplished by proliferation of progenitor cells (regulated by growth factors, PGE(2) and survivin), continuous blood flow through mucosal microvessels, an endothelial "barrier," sensory innervation, and generation of PGs and nitric oxide. Mucosal injury may occur when noxious factors "overwhelm" an intact mucosal defense or when the mucosal defense is impaired. We review basic components of gastric mucosal defense and discuss conditions in which mucosal injury is directly related to impairment in mucosal defense, focusing on disorders with important clinical sequelae: nonsteroidal anti-inflammatory drug (NSAID)-associated injury, which is primarily related to inhibition of cyclooxygenase (COX)-mediated PG synthesis, and stress-related mucosal disease (SRMD), which occurs with local ischemia. The annual incidence of NSAID-associated upper gastrointestinal (GI) complications such as bleeding is approximately 1%-1.5%; and reductions in these complications have been demonstrated with misoprostol, proton pump inhibitors (PPIs) (only documented in high-risk patients), and COX-2 selective inhibitors. Clinically significant bleeding from SRMD is relatively uncommon with modern intensive care. Pharmacologic therapy with antisecretory drugs may be used in high-risk patients (eg, mechanical ventilation >or=48 hours), although the absolute risk reduction is small, and a decrease in mortality is not documented.
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PMID:Gastric mucosal defense and cytoprotection: bench to bedside. 1854 14


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