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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gastrointestinal tract is a major immunologic organ that must be maximally supported during critical illness. Gastrointestinal tissues require direct contact with nutrients to support their own rapid cellular turnover rate and carry out the multitude of metabolic and immunologic functions needed for successful adaptation to stress. Disruption in the ecologic equilibrium of the gastrointestinal tract often occurs during critical illness and the therapies provided. Problems encountered include stress ulcers, intestinal ischemia, bacterial overgrowth, aspiration pneumonia, bacterial translocation, sepsis, and the systemic inflammatory response syndrome. Early enteral nutrition has been shown to be a viable, economic, and physiologically beneficial way to support the gastrointestinal tract during critical illness. The fortification of enteral formulas with glutamine, arginine, or fiber is being studied to determine each one's unique role in the gut and immunologic changes that occur with severe stress.
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PMID:The role of the gut in critical illness. 774 36

Sudden reperfusion of the gut following prolonged ischemia can itself have more deleterious consequences than the ischemia alone. Studies of vasodilator factors influencing the increased flow on reperfusion are therefore of importance. In the present study, a possible role of histamine in the postischemic flow response was examined after a period of total segmental ischemia. The artery supplying the terminal ileum was occluded in anesthetized dogs. Ischemia of 30 min duration was followed by a 30 min reperfusion period (control postischemic flow response), and the arterial blood flow to the segment was measured. After the control postischemic flow response, one of the following drugs was administered intravenously: histamine H1-or H2-blockers (tripelennamine, .5 mg/kg, cimetidine, 10 mg/kg, ranitidine, 2 mg/kg), cromolyn (a mast cell stabilizer, 25 mg/kg), and aminoguanidine (a diamine oxidase blocker, 50 mg/kg). The 30 min ischemia-30 min reperfusion cycle was then repeated (test postischemic flow response). A 30 min mesenteric ischemia-reperfusion period is reproducible once without a significant change in its hemodynamic parameters. The duration and volume of the postischemic flow response were significantly decreased by cimetidine, ranitidine, or cromolyn, and were increased by aminoguanidine. Tripelennamine did not affect the postischemic vasodilator response. At the onset of reperfusion, a release of endogenous histamine occurs from the gut, originating mainly from mast cells. It is proposed that histamine participates in the postischemic flow response through the H2-receptors.
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PMID:Role of histamine in the intestinal flow response following mesenteric ischemia. 774 71

Endothelin is a novel, potent, endogenous vasoconstrictor derived predominantly from endothelium and macrophages. Release of endothelin-1 (ET-1) into biological fluids was determined by radioimmunoassay in pigs undergoing either a hemorrhagic (3 h) or superior mesenteric artery (SMA) occlusion (5 h) shock followed by reperfusion (90 min) or a control group which was observed for 8 h. After surgery, there was a significant increase in ET-1 in jugular and carotid plasma, lymph, and ascitic fluid in all three models. The portal plasma ET-1 level was significantly increased (p < .05, assessed by the Spearman rank coefficient rho) in both shock models, but no significant increase was noted in the control group. In the SMA occlusion shock model, four pigs died within 30 min of reperfusion, and these animals had a much higher level of portal ET-1 (22.3 +/- 5.5 fmol/mL) than the two pigs that were alive by the end of the observation period (11.5 +/- 1.3 fmol/mL). Reperfusion in the SMA occlusion shock model induced a critical form of circulatory shock characterized by hypotension, decreased cardiac output, and decreased left and right ventricular stroke work index, and death occurred usually within 90 min. Reperfusion of the shed blood in the hemorrhagic shock model almost normalized the hemodynamic derangements caused by the hypovolemia (with the exception of RVSWI), and the portal plasma and ascitic ET-1 levels decreased. These results indicate that ET-1 is released from the gut in response to both general hypoperfusion and selective intestinal ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelin and hemodynamic responses to superior mesenteric artery occlusion shock and hemorrhagic shock in pigs. 774 37

Ischemia and reperfusion of the gut may be an important etiological factor in the development of multiple organ failure. We have used a hemorrhagic and a superior mesenteric artery (SMA) occlusion shock model in pigs to estimate the effect of ischemia and reperfusion on intestinal morphology, mucosal permeability, and the occurrence of bacterial or endotoxin translocation. Mucosal ulceration and necrosis were found in the SMA shock model, while the morphological changes were less pronounced in the hemorrhagic shock model. Scanning electron microscopy showed shrinkage of the villi and plugging of the colonic crypts in both shock models. Enterocyte cell kinetics was investigated using 5-bromo-2'-deoksyuridine (BrdU) incorporation and immunovisualization by anti-BrdU antibodies. Cell renewal was almost completely lost from the jejunum to the rectum in both shock models. Intramucosal pH was measured using a tonometer placed in the terminal ileum. Segments of intestinal mucosa were mounted in Ussing chambers, and permeability was measured using radiolabeled probe molecules of differing molecular weights. Augmented molecular flux of inulin (M(r) 5.000) and mannitol (M(r) 182) and loss of short circuit current (Isc) and transepithelial potential difference (PD) were found in mucosae from both shock models. Endotoxin was demonstrated in the ascitic fluid in both shock models; 9.5 (2.7-14.3) (median and 95% confidence interval) EU/mL in the SMA occlusion model and 16.0 (4.9-29.4) EU/mL in the hemorrhagic shock model), but the levels were not significantly higher than in the control model 6.5 (4.3-34.0) EU/mL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in mucosal morphology and permeability, but no bacterial or endotoxin translocation takes place after intestinal ischemia and early reperfusion in pigs. 774 38

The pigs with allograft were divided into 5 groups according to the different immunosuppressive regimens. Acute rejection of allograft occurred in animals not treated with immunosuppressive agents or treated with low dose of cyclosporine (CsA). There was no rejection developed in the pigs treated with high dose CsA or low dose CsA and tripterygium wilfordii (TW). No evidence of chronic rejection was detected in animals with continued administration of TW after living longer than 100 days when the immunosuppressive treatment was discontinued. A woman with enterocolitis, ileus and short-gut syndrome received a complete cadaveric small bowel transplantation in march 12, 1994. The graft had 6 minutes for warm ischemia and 9 hours and 45 minutes for cold ischemia. The immunosuppressive therapy consisted of CsA, TW and methylprednisolone. The patient is alive and the function of graft is normal.
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PMID:[Experimental and clinical studies of small bowel allotransplantation]. 777 36

Our previous work has implicated platelet activating factor (PAF)-induced neutrophil (PMN) priming and increased CD11b/CD18 receptor expression in the pathogenesis of lung injury following gut ischemia/reperfusion (I/R). In this model CD11b blockade abrogates lung injury but does not alter PMN priming or pulmonary leukosequestration. We, therefore, hypothesized that PAF-stimulated PMN priming and CD11b expression are insufficient to promote lung PMN sequestration. Normal rat PMNs, labeled with 51Cr, were incubated with PAF (10 ng/ml) to induce priming for superoxide (O2-) generation and enhance CD11b expression. Gut I/R animals underwent superior mesenteric artery occlusion for 45 min. 51Cr-labeled PMNs (2 x 10(7)) were injected iv. Study groups, consisting of (a) normal/control, (b) sham/laparotomy, and (c) gut I/R, were given either normal or PAF-treated PMNs. PAF-primed PMNs had increased 2- release and CD11b expression, but did not sequester in the lungs of normal rats. However, following gut I/R PAF-treated PMNs sequestered in the pulmonary bed. These data suggest that PAF priming for O2- generation and increased CD11b expression are insufficient alone to promote PMN sequestration in the lung. Rather, additional factors generated by gut I/R are necessary for this process.
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PMID:PMNs primed for superoxide release and increased CD11b expression do not sequester in normal lung. 779 34

Our in vivo model of mesenteric ischemia/reperfusion (I/R) has shown that the gut serves as a priming bed for neutrophils (PMN). Activation of phospholipase A2 (PLA2) during ischemia temporally precedes PMN sequestration in the gut and the appearance of primed PMN in the portal circulation. Therefore, we hypothesized that reperfused gut secretes platelet activating factor (PAF) via PLA2 activation that is responsible for increased PMN chemotaxis and priming for superoxide (O2-) generation. Sprague-Dawley rats underwent gut ischemia/reperfusion (45 min SMA occlusion/2 hr reperfusion) or sham laparotomy. Distal ileum was harvested, rinsed with bacteriostatic saline/neomycin, and incubated for 1 hr at 37 degrees C in RPMI 1640 and the cell-free supernatant was collected. Normal human PMNs, isolated by plasma-Percoll gradients, were pretreated with or without a PAF receptor antagonist (WEB 2170). Chemotaxis toward gut supernatant was then measured by the agarose method. Additionally, PMNs were preincubated with or without WEB 2170 and their O2- release in response to 1 microM FMLP was measured by the Vmax of SOD-inhibitable cytochrome c reduction. Reperfused gut produced a chemotactic index of 2.1 +/- 0.1 compared to 0.2 +/- 0.9 following sham laparotomy (P < 0.05); this was reduced to 0.4 +/- 0.9 with PAF receptor blockade. Similarly, gut I/R supernatant primed PMNs for O2- (P < 0.05) compared to laparotomy, and this effect was abrogated by a PAF antagonist. These data suggest that reperfused gut can elaborate PAF which chemoattracts and primes PMNs for O2- generation.
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PMID:Reperfused gut elaborates PAF that chemoattracts and primes neutrophils. 779 40

Four cases of acute gut ischemia in elderly patients due to non-occlusive disease (NOD) are presented. Bowel necrosis occurred after episodes of hypotension in the course of myocardial infarction, arrhythmias and sepsis. Symptoms and clinical findings were blurred by the underlying extraintestinal disease. Angiography showed coexistent atherosclerosis but no occlusion of the major celiac and mesenteric vessels. At laparotomy (three cases) or autopsy (one case) extensive small and large bowel necroses were detected. Early laparotomy (possibly preceded by laparoscopy) is recommended for patients with suspected acute gut ischemia even if angiography fails to reveal occlusion of the large splanchnic arteries.
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PMID:[Nonobstructive mesenteric ischemia--a diagnostic problem in internal intensive care]. 779 21

The potential beneficial effect of hepatocellular glutathione against inflammatory liver damage was investigated in a model of endotoxin-enhanced ischemia-reperfusion injury. Animals were subjected to 20 min of hepatic ischemia, followed by 4 hr of reperfusion. The injection of 0.5 mg/kg Salmonella enteritidis endotoxin potentiated liver injury and the postischemic oxidant stress, as indicated by increased plasma levels of glutathione disulfide. Depletion of hepatic glutathione levels by > 90% with phorone and inhibition of glutathione synthesis with buthionine sulfoximine further increased liver injury in this model, as indicated by enhancement of plasma alanine aminotransferase activities from 2,234 +/- 122 U/L to 4,024 +/- 282 U/L. Continuous infusion of a glutathione (GSH) solution in GSH-depleted animals (22 mumol/kg/hr) attenuated reperfusion injury by 55%. In vitro experiments demonstrated the capability of GSH to react rapidly with reactive oxygen species, such as hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). Only H2O2 oxidized GSH quantitatively to its disulfide; HOCl oxidized GSH to higher oxidation states. These data support the hypothesis that the enhanced release of hepatocellular GSH functions as a defense mechanism against reactive oxygen species generated by inflammatory cells during endotoxemia and reperfusion. This internal defense system of the liver may be of general importance in preventing, or at least limiting, liver damage by reactive oxygen generated in particular by Kupffer cells during their physiological function to remove gut-derived endotoxin and bacteria.
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PMID:Beneficial effects of extracellular glutathione against endotoxin-induced liver injury during ischemia and reperfusion. 783 22

Intestinal ischemia-reperfusion (I/R) provokes polymorphonuclear neutrophil (PMN)-mediated lung injury via a process characterized by circulating PMN priming, pulmonary PMN sequestration, and increased microvascular leak in the lung. We found in rats subjected to intestinal I/R (ischemia 45 min and reperfusion 6 h) that 1) intestinal phospholipase A2 (PLA2) was activated during ischemia, 2) circulating PMN priming (assessed by superoxide production with N-formyl-Met-Leu-Phe) occurred after 1 h reperfusion, and 3) exaggerated 125I-labeled albumin lung leak occurred after 2 h reperfusion, compared with sham-treated animals (P < 0.05). Treatment with a PLA2 inhibitor, quinacrine, within 15 min of reperfusion reversed the exaggerated gut PLA2 activity and abrogated subsequent PMN priming and lung leak (P < 0.05). However, when quinacrine was administered after 2 h of reperfusion, circulating PMN priming and lung leak continued to evolve despite suppression of intestinal PLA2 activity. We conclude that intestinal PLA2 activation may be a prerequisite for the sequelae of circulating PMN priming and pulmonary microvascular leak observed after intestinal I/R.
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PMID:Gut phospholipase A2 mediates neutrophil priming and lung injury after mesenteric ischemia-reperfusion. 790 Aug


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