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

Ischemia and reperfusion of the lower torso lead to leukotriene- and neutrophil (PMN)-dependent lung injury characterized by lung PMN sequestration, increased permeability, and noncardiogenic edema. It is thought that PMNs require adhesion to endothelium to alter barrier function. This study tests the role of CD 18, the PMN adherence receptor, in mediating lung permeability after lower torso ischemia and reperfusion. Anesthetized rabbits (n = 9) underwent 3 hours of bilateral hind limb ischemia. Ten minutes after the release of the tourniquets, plasma leukotriene B4 levels increased to 395 +/- 85 pg/ml, higher than 129 +/- 35 pg/ml in controls (n = 9, p less than 0.01). At this time there was a reduction in circulating white blood cells (x 10(3)), 3.56 +/- 0.49/mm3 relative to 6.07 +/- 0.61/mm3 in controls (p less than 0.01). PMNs were sequestered in the hind limbs, indicated by increased myeloperoxidase activity of 1.06 +/- 0.19 units/g compared with 0.56 +/- 0.09 units/g in controls (p less than 0.05). Four hours after tourniquet release, PMNs were sequestered in the lungs, 52 +/- 4 PMNs per 10 high-power fields, a value higher than 31.5 +/- 3 PMNs per 10 high-power fields in controls; bronchoalveolar lavage fluid protein content increased to 554 +/- 90 micrograms/ml relative to 277 +/- 46 micrograms/ml in controls; and there was lung edema, measured by increased wet weight-to-dry weight ratios of 5.19 +/- 0.10, higher than 4.29 +/- 0.21 in controls (all p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of neutrophil adherence receptors (CD 18) in lung permeability following lower torso ischemia. 135 25

This study tested the hypothesis that preventing neutrophil adhesion during reperfusion, by blocking either the neutrophil membrane CD18 integrin complex or its endothelial and myocyte ligand, intercellular adhesion molecule-1 (ICAM-1), would reduce myocardial inflammation and edema and improve reflow and ventricular function after heart preservation and transplantation. After cardioplegia and insertion of a left ventricular balloon, rabbit hearts were heterotopically transplanted into recipient rabbits either immediately (immediate, n = 12) or after preservation in 4 degrees C saline (3 hours of ischemia, n = 33). Forty-five minutes before reperfusion, recipients of preserved hearts received intravenous infusions of either saline (vehicle, n = 13), anti-CD18 monoclonal antibody (Mab) R15.7 (2 mg/kg) (anti-CD18, n = 10), or anti-ICAM-1 Mab R1.1 (2 mg/kg) (anti-ICAM, n = 10). During 3 hours of reperfusion the slope of the peak-systolic pressure-volume relation and its volume-axis intercept, the exponential elastic coefficient of the end-diastolic pressure-volume relation, the unstressed ventricular volume, and the time constant of the exponential left ventricular pressure decay after dP/dtmin were serially measured. Myocardial blood flow was measured with microspheres from which coronary vascular resistance was calculated. After explanation, the degree of myocardial inflammation, estimated by tissue neutrophil sequestration (myeloperoxidase assay) and myocardial water content were determined. Within each group no significant differences in measurements made at 1, 2, and 3 hours of reperfusion were noted. Compared with the immediate transplantation group, the vehicle group demonstrated a significant increase in myeloperoxidase activity (3380 +/- 456 versus 1712 +/- 552 microU/gm, p < 0.05), coronary vascular resistance (115.5 +/- 13.4 versus 70.5 +/- 10.6 U/gm, p < 0.05), and myocardial water content (79.8% +/- 0.4% versus 75.6% +/- 1.3%, p < 0.05), a significant decrease in unstressed ventricular volume (a leftward shift in the end-diastolic pressure-volume relation) (-0.49 +/- 0.24 versus 0.28 +/- 0.21 ml, p < 0.05), and a marked prolongation in exponential left ventricular pressure delay after dP/dtmin (156.64 +/- 3.81 versus 37.25 +/- 3.34 msec, p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Complete prevention of myocardial stunning, contracture, low-reflow, and edema after heart transplantation by blocking neutrophil adhesion molecules during reperfusion. 136 May 56

Oxygen-derived free radicals and leukocytes have been implicated in the pathogenesis of ischemia-reperfusion injury. This study aimed at determining, by using biochemical and histochemical techniques, whether an accumulation of neutrophils occurs in the ischemic reperfused rat liver and whether superoxide free radicals play a role in mediating this neutrophil accumulation. Hepatic ischemia was induced by occluding blood supply to the left and median lobes, and reperfusion was reinstituted by releasing the occlusion. Myeloperoxidase activity of the liver was measured with a tetramethylbenzidine-H2O2 assay after removal of glutathione (by dialysis) and in the presence of 3-aminotriazole (catalase inhibitor). A modification of Graham and Karnovsky's method was used to stain neutrophils in liver frozen sections, and the number of neutrophils was counted. Results showed that ischemia-reperfusion of the liver produced a 4.4-fold increase in myeloperoxidase activity (from 0.073 +/- 0.009 to 0.320 +/- 0.017 units/mg liver, means +/- SE), which was proportional to the number of neutrophils (3.1-fold increase from 18 +/- 7 to 57 +/- 4 cells/mm2) in the liver tissue. Pretreatment with long-acting superoxide dismutase significantly attenuated the elevated myeloperoxidase activity and the number of neutrophils. These results indicate that reperfusion after a period of ischemia induces an accumulation of neutrophils in the liver, and superoxide anion free radicals are important mediators in the mechanism of this neutrophil accumulation.
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PMID:Neutrophil accumulation in ischemic reperfused rat liver: evidence for a role for superoxide free radicals. 137 65

An in vitro model was designed to study the role of ischemia/reperfusion and endothelium-derived oxygen free radicals on neutrophil adhesion, with particular interest in the endothelial adhesion molecules involved. Human umbilical vein endothelial cells were submitted to 5 h hypoxia followed by various times (20 min to 24 h) of reoxygenation. Human resting neutrophils were added to monolayers for the last 15 min of reoxygenation. Adherence was evaluated by myeloperoxidase assay. Under these conditions, we found an increased adhesion of neutrophils with two peaks after 20 min and 4 h reoxygenation. This was correlated with the respective expression of the preformed granule membrane protein 140 (GMP-140) and of the de novo synthesized endothelial leukocyte adhesion molecule 1 (ELAM-1) on endothelial surface. Superoxide dismutase and/or catalase, or oxypurinol added to cultures before hypoxia efficiently prevented neutrophil adhesion. These results underline the crucial role played by endothelial oxy radicals at reoxygenation in adhesion of leukocytes, which could lead to an amplification of the oxidative stress injury. The protection offered by free radical scavengers emphasizes the potential therapeutic use of antioxidants in postischemic vascular disorders.
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PMID:Hypoxia/reoxygenation stimulates endothelium to promote neutrophil adhesion. 137 20

We examined the role of C activation in ischemia reperfusion injury by inhibiting C activation in a rat model of mesenteric arterial occlusion. In anesthetized rats, 60 min of mesenteric arterial occlusion was followed by 3 h of reperfusion. PBS alone or containing soluble C receptor 1 (3 or 6 mg) was administered i.v. Controls underwent laparotomy without ischemia. Relative serum C activities were assessed by hemolytic assay, neutrophil (polymorphonuclear leukocyte) sequestration by tissue content of myeloperoxidase (MPO) activity, intestinal mucosal injury by histologic grading, lung vascular permeability by the ratio of bronchoalveolar lavage to blood concentration of radiolabeled BSA, and endothelial cell injury was quantified by measurement of plasma factor VIII-related Ag. After reperfusion, PBS-treated animals had increased intestinal MPO (0.048 +/- 0.007 U/g) compared to sham (0.022 +/- 0.005 U/g (p less than 0.05)) and intestinal mucosal injury score (2.490 +/- 0.221) compared to sham (0.331 +/- 0.045 (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion reduced intestinal MPO (0.017 +/- 0.003 U/g (p less than 0.05)) and mucosal injury (1.733 +/- 0.168 (p less than 0.05)) compared to PBS control. PBS-treated animals also demonstrated increased lung MPO (0.314 +/- 0.025 U/g vs 0.085 +/- 0.018 in sham (p less than 0.05)) and increased lung permeability (bronchoalveolar lavage/blood cpm 11.32 +/- 1.35 x 10(-3) vs sham 2.22 +/- 0.19 x 10(-3) (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion or at reperfusion reduced the lung permeability (bronchoalveolar lavage/blood cpm 3.90 +/- 0.79 x 10(-3) and 5.08 +/- 0.75, respectively (both p less than 0.05)) compared to PBS control, but did not reduce lung MPO (0.342 +/- 0.031 U/g and 0.246 +/- 0.025), respectively. Treatment with sCR1 also reduced the release of factor VIII-related Ag, 5-day mortality, and C hemolytic activity. In this model, C is a major mediator of intestinal injury and extraintestinal injury.
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PMID:Soluble complement receptor type 1 ameliorates the local and remote organ injury after intestinal ischemia-reperfusion in the rat. 138 51

The purpose of the present investigation was to establish whether pretreatment with selenium enhances the stores of selenium-dependent glutathione peroxidase in the tissues and to verify if and to what extent alterations of mechanical and biochemical cardiac properties induced by ischemia in the myocardium may be thus prevented. Ten rats had sodium selenite (6 micrograms/day) added to their drinking water for 4 weeks, while 10 control rats received no treatment. At the end of 4 weeks, the hearts were perfused by the Langendorff technique with oxygenated Krebs-Henseleit solution at a rate of 10 ml/min for 30 minutes at 37 degrees C. Ischemia was then induced by reducing the perfusion to 1 ml/min for 60 minutes; reperfusion followed at the control rate for a further 30 minutes. Isometrically developed pressure and its maximum first derivative at different ventricular volumes was measured before and after the ischemic period. Lactate and creatine kinase activity were measured in the effluent throughout. Tissue concentrations of adenine nucleotides and creatine phosphate and lutathione peroxidase activity were estimated after reperfusion. The rats treated with selenium showed a wide-spread increase in the activity of Se-dependent glutathione peroxidase in all tissues. There was an improved recovery of ventricular contraction during reperfusion and an increased myocardial content of adenine nucleotides and creatine phosphate. During reperfusion, the loss of creatine kinase into the perfusate was less in the treated animals, and there was a similar trend for the production of lactate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effect of selenium in cardiac ischemia and reperfusion. 142 Sep 51

By using pharmacological tools, the biological actions of adenosine (ADO) were manipulated in rat intestine that had been rendered ischemic for 5 or 15 minutes and reperfused for 1 or 24 hours. With 100 microM ADO topically administered for 30 minutes after ischemia and then washed out, intestinal arteriolar blood flow (BF) and tissue ATP were restored to preocclusion levels, and histological damage was minimal after 1 hour of reperfusion. For comparison, with vehicle treatment after ischemia, BF was reduced by 50%, tissue ATP was reduced by 50%, myeloperoxidase levels in the intestine and lung were increased at least twofold, and mucosal villi were shortened and thickened after 1 hour of reperfusion. Furthermore, with vehicle treatment, both baseline BF and reactivity to endothelium-dependent (acetylcholine) and endothelium-independent (2-chloroadenosine) vasodilators were significantly depressed after 24 hours of reperfusion. In contrast, with ADO, baseline BF remained near normal, and vascular reactivity to 2-chloroadenosine and acetylcholine was preserved after 24 hours. The salutary effect of ADO on BF was reduced by simultaneous application of the antagonist 8-phenyltheophylline or the cellular uptake inhibitor dipyridamole. The nonmetabolized agonist 2-chloroadenosine, the purine precursor aminoimidazole carboxamide riboside, or dipyridamole alone all had favorable effects relative to the vehicle, but all were less potent than ADO. The conclusions are as follows: 1) Endogenous ADO modulates the inflammatory response evoked by intestinal reperfusion because aminoimidazole carboxamide riboside or dipyridamole, which increases its availability, generally had favorable effects, whereas 8-phenyltheophylline tended to have opposite effects. 2) Exogenous ADO arrests most of the inflammatory changes associated with reperfusion by mechanisms that include both extracellular (e.g., receptor-mediated vasodilation and granulocyte inhibition) and intracellular (e.g., restoration of ATP) actions. 3) The effectiveness of ADO-related compounds even when administered after ischemia attests to the practicality of salvaging ischemic bowel, at least in some conditions.
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PMID:Extracellular and intracellular actions of adenosine and related compounds in the reperfused rat intestine. 149 13

The effects of two dibenzocyclooctene lignans on peroxidative damage of aging and ischemic rat brain were studied. Incubation of eight-month-old rat brain mitochondria and membrane suspension with Fe(2+)-cysteine resulted in the formation of malondialdehyde (MDA) and decrease of ATPase activity. Schisanhenol (Sal) (10(-4) M) completely inhibited the peroxidative damages of brain mitochondria and membrane of rats. The swelling and disintegration of brain mitochondria, as well as the reduction of brain membrane fluidity induced by Fe(2+)-cysteine were also prevented by Sal. The results of imitative experiment of ischemia and reperfusion of brain mitochondria and membrane in vitro indicated that Sal significantly impeded production of MDA and loss of ATPase activity induced by reoxygenation following anoxia. Oral administration of Sal induced increase of cytosol glutathione-peroxidase of brain in mice under the condition of reoxygenation following anoxia. The other compound schizandrin (Sin B) also has similar activity. But its potency is weaker than that of Sal. All these results indicate that Sal and Sin B have protective action against oxidative stress.
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PMID:Antioxidant activity of two dibenzocyclooctene lignans on the aged and ischemic brain in rats. 153 86

We characterized the release of arachidonic acid (AA) metabolites in lung effluent following lung ischemia-reperfusion since they may contribute to the pathophysiology of reperfusion lung injury. The left pulmonary artery of rabbits (N = 5) was occluded for 24 hrs with a surgically implanted vascular clip. At 24 hrs, the heart and lungs were removed en bloc and perfused with Ringers-albumin (0.5 gm%) at 60 ml/min while statically inflated with 95% O2-5% CO2. The lipid fraction of the lung effluent was concentrated using the Bligh-Dyer extraction and analyzed by gradient RP-HPLC. Samples obtained in the first minute of reperfusion showed significant increases in LTB4 (+180%), LTC4 (+3600%), 15-HETE (+370%), 5-HPETE (+270%), PGE2 (+140%), 6-keto-PGF1 alpha (+110%) and 12-HHT (+160%) compared to the effluent from the right control lung. The reperfusion-induced increases in LTB4, LTC4, LTD4 and 15-HETE were inhibited greater than or equal to 70% by pretreatment with the 5-LO inhibitors L663,536 or L651,392. The increases in lipid concentrations corresponded to significantly increased pulmonary arterial pressure from a baseline value of 9.5 +/- 0.3 to 29.3 +/- 2.9 (cmH2O) during the first min of reperfusion. The pulmonary arterial pressure remained elevated for at least 20 min of reperfusion. Reperfusion also resulted in PMN uptake (assessed by lung tissue myeloperoxidase content) in the reperfused lung versus control lung (25.0 +/- 2.4 vs. 10.5 +/- 2.5 units). The generation of lipoxygenase metabolites during the initial phase of reperfusion may contribute to post-reperfusion PMN uptake and pulmonary vasoconstriction.
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PMID:Generation of 5-lipoxygenase metabolites following pulmonary reperfusion in isolated rabbit lungs. 160 20

Immobilized enzymes are widely used in the clinical laboratory to assay several analytes and enzymes. The use of immobilized enzymes makes these reagents recoverable, disposable and in most cases increases their stability and catalytic activity. In conjunction with bioluminescent enzymes (firefly and bacterial luciferases) and chemiluminescent catalyst (peroxidase) we set up high-sensitive flow sensors based on the use of nylon tube coil or epoxy methacrylate column as solid support. For in-vivo determination a suitable microdialysis probe inserted directly into brain or blood allows continuous measurement of extracellular lactate levels by means of a bioluminescent flow detector system. This procedure performs more measurements in the same time interval than other systems (HPLC), e.g. to give a detailed description of the effects of ischemia, or other pathological events, on lactate concentration in the brain.
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PMID:Microdialysis and luminescent probe: analytical and clinical aspects. 164 15


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