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

Focal cerebral ischemia was produced by occluding the left middle cerebral artery in 769 rats. Permeability of the blood-brain barrier to small or large molecules was evaluated qualitatively using Evans blue or sodium fluorescein and quantitatively using the transfer indexes of iodine-125-labeled bovine serum albumin or [14C]sucrose. Water content was determined using wet and dry weights and sodium and potassium contents using flame photometry. Cortical tissue in the middle cerebral artery territory was sampled less than or equal to 14 days after occlusion. A significant increase in the albumin transfer index was first found 12 hours after occlusion, and the index remained approximately the same until water content peaked 3 days after occlusion. In contrast, the sucrose transfer index increased gradually, significantly correlated with increases in the water and sodium contents. Tissue staining by sodium fluorescein was more extensive than that by Evans blue. As edema fluid decreased gradually 4-10 days after occlusion, the albumin and sucrose transfer indexes increased markedly. These findings indicate that disruption of the blood-brain barrier to small molecules is accompanied by accumulation of edema fluid during the later stages of ischemia. Opening of the barrier to serum protein is probably related to the resolution of edema.
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PMID:Brain edema and cerebrovascular permeability during cerebral ischemia in rats. 169 34

Transient forebrain ischemia of 30 min duration was produced in anaesthetized rats by four-vessel occlusion. After survival periods of 3 h to three days brains were perfusion-fixed and sections through the mid-dorsal hippocampus were processed for conventional staining and immunohistochemical analysis. Neuronal damage in the hilus was manifested 3-8 h after ischemia; neurons in the CA1 and CA2 sector suffered delayed neuronal death after 48-72 h whereas the dentate gyrus and the CA3 sector were normal. Vasogenic edema formation was visualized using antibodies against rat serum-proteins, serum albumin and immunoglobulins. By 3 h after ischemia, only faint and diffuse serum-staining was detected. At 8 h survival, weak astrocytic-staining was present. After 24-72 h CA1-CA2 exhibited massive serum extravasation. The molecular layer of the dentate gyrus showed edema formation in the absence of granule cell damage. The glial reaction was studied using antibodies against glial fibrillary acidic protein, vimentin and S-100 protein. Glial fibrillary acidic protein and S-100 protein-staining increased in areas with either edema or neuronal damage. In contrast, changes in vimentin were only detected in areas with neuronal necrosis. The observations demonstrate that following 30 min of ischemia neuronal damage is accompanied by changes in blood-brain barrier function and reactive glial alterations. The dissociation between neuronal necrosis and astroglial hypertrophy and hyperplasia reflects differences in cellular responsiveness which constitute inherent features of postischemic hippocampal injury.
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PMID:Immunohistochemical study of glial reaction and serum-protein extravasation in relation to neuronal damage in rat hippocampus after ischemia. 170 95

The effect of cyclosporine on hepatic ischemia was investigated. Hepatic ischemia was produced for 90 min in mongrel dogs. Experimental dogs were divided into three groups as follows: group A (control group), group B (CsA pretreatment group), group C (CsA posttreatment group). CsA was administered at a dose of 10 mg/kg body weight/day for 3 days in the pre- or postoperative period. Survival rates were 61.5% in group A, 84.6% in group B, and 30.8% in group C. Enzymatic activity such as aspartate aminotransferase and lactate dehydrogenase was highest in group C, lowest in group B, and intermediate in group A. Opposite results were obtained for serum albumin concentrations. The mechanisms of the effect was investigated using a 60-min hepatic ischemia model. Serum levels of beta-glucosidase and beta-galactosidase in group B were lower than those in group A and group C. Electronmicroscopic specimens taken at 16 h after 60-min hepatic ischemia demonstrated that the extent of ischemic injury was mildest in group B. The present study demonstrated a beneficial effect on hepatic ischemia of CsA administered for 3 days prior to the ischemia. One of the mechanisms for this beneficial effect could be the stabilization of lysosomal membranes. These results suggest that CsA should be administered to a donor before organ harvesting for liver transplantation because of this beneficial effect.
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PMID:Beneficial effect of cyclosporine pretreatment in canine liver ischemia. Enzymatic and electronmicroscopic studies. 190 40

Ischemia-reperfusion lung injury limits lung transplantation. Neutrophil activation and/or xanthine oxidase-mediated purine degradation may cause toxic oxygen metabolite production and lung injury. We investigated whether circulating blood elements are involved in the pathogenesis of ischemia-reperfusion lung injury. Isolated rat lungs were perfused with physiological salt solution (PSS) stabilized with Ficoll until circulating blood elements were not detected in the lung effluent. Lungs were then rendered ischemic by stopping ventilation and perfusion for 45 min at room temperature. Lung injury occurred and was quantitated by the accumulation of 125I-bovine serum albumin into lung parenchyma and alveolar lavage fluid during reperfusion. Lung injury occurred, in the absence of circulating blood elements, when ischemic lungs were reperfused with PSS-Ficoll solution alone. Reperfusion with whole blood or PSS-Ficoll supplemented with human or rat neutrophils did not increase lung injury. Furthermore, during lung ischemia, the presence of neutrophils did not enhance injury. Experiments using PSS-albumin perfusate and quantitating lung injury by permeability-surface area product yielded similar results. Microvascular pressures were not different and could not account for the results. Toxic O2 metabolites were involved in the injury because addition of erythrocytes or catalase to the perfusate attenuated the injury. Thus reperfusion after lung ischemia causes injury that is dependent on a nonneutrophil source of toxic O2 metabolites.
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PMID:Neutrophils are not necessary for induction of ischemia-reperfusion lung injury. 231 80

Injection of sonic extracts of Bordetella parapertussis into the shaved backs of guinea pigs produced hemorrhagic necrosis, which previously has been attributed to the action of heat-labile toxin. As heat-labile toxin was purified from this crude mixture, its ability to induce hemorrhagic lesions decreased significantly. However, ischemic lesions were apparent after injection of the purified toxin. These lesions, while not hemorrhagic in nature, were marked by erythema surrounded by a region in which the ischemia was apparent. Exogenous agents were found to alter the nature of the skin lesion induced by heat-labile toxin. The lipid A portion of endotoxin in combination with heat-labile toxin caused hemorrhagic lesions surrounded by a ring of ischemia, whereas bovine serum albumin increased the area of erythema. While the nature of lesions induced by heat-labile toxin was affected by exogenous agents, the diameter of ischemia produced by the toxin was found to be independent of the presence of these agents and was linear with toxin dose. These results indicate that induction of hemorrhagic necrosis may not be a reliable indicator of heat-labile toxin activity. Instead, measurement of the ischemic lesion produced by heat-labile toxin may be a useful assay for the toxin.
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PMID:Effects of exogenous agents on the action of Bordetella parapertussis heat-labile toxin on guinea pig skin. 232 23

Effects of diltiazem on coronary vascular functional integrity were assessed in isolated rabbit hearts during reperfusion after 30 min of global, no-flow ischemia. External detection of radiolabeled albumin, [125I]bovine serum albumin ([125I]BSA), and compartmental-model analysis were used to estimate the mean transit time of [125I]BSA (tBSA), vascular volume (V1), and vascular into extravascular space clearance (F21) for [125I]BSA. Perfusion pressure, left ventricular (LV) end-diastolic pressure, LV developed pressure, maximum +dP/dt, and V1 remained constant during 5 h of continuous perfusion, while tBSA and F21 gradually increased (1.5 and 2.4 times baseline, respectively). Diltiazem, 4 microM, increased total water content (8.5%) and decreased perfusion pressure (11%), LV developed pressure (22%), and +dP/dt (24%) in nonischemic control experiments, but did not significantly affect estimates of V1, extracellular space, tBSA, or albumin permeation. During reperfusion after 30 min of ischemia, V1 increased 40% and perfusion pressure increased 60%, while tBSA and F21 increased three and eight times baseline, respectively. LV developed pressure and +dP/dt returned to control levels, even though the water content and extracellular space of ischemic hearts were increased significantly. Diltiazem, 4 microM, blocked ischemia-reperfusion-induced increases in water content, extracellular space, vascular resistance, V1, and vascular permeability to [125I]BSA, without reducing LV developed pressure or +dP/dt relative to nonischemic diltiazem controls. These results suggest that protection of ischemic myocardium by diltiazem is mediated, at least in part, by preservation of vascular functional integrity.
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PMID:Coronary vascular hemodynamic and permeability changes during reperfusion after no-flow ischemia in isolated, diltiazem-treated rabbit hearts. 241 Jun 70

Tritiated thymidine autoradiography was used to measure cellular proliferation after ischemic injury in gerbil brain. Gerbils were subjected to bilateral occlusion of the common carotid arteries which resulted in areas of necrosis, or infarcts, in the posterior thalamus or midbrain. From 12 h to 10 days following the ischemia, gerbils were injected with 3H thymidine, sacrificed 4 h later, and the brains sectioned. In order to identify astrocytes and monocytes/macrophages, immunocytochemistry was performed prior to autoradiography, using antisera against glial fibrillary acidic protein and endothelial-monocyte reticuloendothelial antigen, respectively. Immunocytochemistry was also used to visualize microvessel laminin, myelin, and leakage of serum albumin. Lastly, a histochemical procedure for acid phosphatase activity was employed to verify cellular phagocytic activity in the wound. A reproducible sequence of reactions took place during the first 10 days after ischemia. Early changes included leakage of albumin and myelin breakdown, followed by arrival of monocytes at 2 days and their differentiation into macrophages by 5 days. These cells exhibited intense proliferation from 2 to 6 days post-ischemia. Microvessel endothelial cells were maximally labeled at 4 days post-ischemia. Hypertrophied astrocytes were apparent at 2 days and proliferated from 3 to 7 days post-ischemia, and by 10 days the wound was replaced by a "glial scar".
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PMID:Cell proliferation after ischemic injury in gerbil brain. An immunocytochemical and autoradiographic study. 241 99

We studied the effect of iv administration of biodegradable macromolecules on microvascular permeability after ischemia-reperfusion injury in a rat gastrocnemius model. After 2 h of tourniquet ischemia of the rats' hind limb, groups of animals were given iv lactated Ringer's solution (RL), serum albumin 5%, or varying MW fractions of biodegradable macromolecules of hydroxyethyl starch (HES), glycogen, and dextran. At the conclusion of the 24-h reperfusion period, the rat gastrocnemius muscles were collected. Water and K+ differences between the ischemic and control muscles were compared. Rats given a 100,000 to 300,000-dalton fraction of HES had significantly decreased water content (5.1 +/- 3.4%) when compared to rats receiving RL (8.3 +/- 2.2, p less than .01), less than 100,000 dalton HES (8.3 +/- 3.2, p less than .05), less than 300,000 glycogen (7.9 +/- 2.5, p less than .01), or dextran 150,000 (8.3 +/- 1.5, p less than .05). Rats given 100,000 to 300,000-dalton HES also had significantly higher ischemic muscle K+ content as compared to the nontourniquet control (difference 14.2 +/- 9.7 mEq/g) than rats receiving any of the other solutions (range 32.5 to 39.3) except the 300,000 to 1,000,000-dalton fraction of HES. Regression analysis comparison of K+ difference to the histologic evaluation of the muscles on the criteria of polymorphonuclear infiltration and interstitial edema (0, best; 3, worst) had a Pearson correlation coefficient of r = .73. Reduction of abnormally increased microvascular permeability may be accomplished by the iv use of appropriate sized biodegradable macromolecules.
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PMID:Macromolecules reduce abnormal microvascular permeability in rat limb ischemia-reperfusion injury. 248 Feb 5

Accumulation of free fatty acids and their esters resulting from the degradation of membrane phospholipids is one of the major causes for the myocardial dysfunction during ischemia and reperfusion. In this communication, we have studied the possible physiological role played by fatty acid binding protein (FABP) in stimulating key enzymes involved in phospholipid biosynthesis. Purified rat heart FABP bound a maximum of either 2 mol of [1- 14C]palmitoyl coenzyme A (CoA), oleoyl CoA, or oleic acid per mol of FABP as observed by Scatchard analysis. FABP caused a threefold increase in the incorporation of [1- 14C]palmitoyl CoA into phosphatidic acid as compared to only a 1.5-fold increase by bovine serum albumin (BSA). Myocardial FABP also enhanced acyl CoA monoacylglycerophosphorylcholine acyl transferase minimally at a substrate concentration (greater than 200 microM), the activity of this enzyme was enhanced 4.5- and 2-fold by FABP and BSA, respectively. The maximum stimulation of the enzyme activity took place at the fatty acyl CoA concentration where inhibition of the enzyme activity is usually observed due to the surfactive property of acyl CoAs. These results thus indicate that under abnormal pathophysiological conditions such as ischemia, when acyl CoA concentration increases, FABP may protect acyl CoA monoacylglycerophosphorylcholine acyl transferase as well as stimulate glycerophosphate acyl transferase to limit the loss of membrane phospholipids, suggesting a possible role of FABP in phospholipid biosynthesis.
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PMID:Possible physiological role of myocardial fatty acid binding protein in phospholipid biosynthesis. 251 96

Recent investigations have indicated the presence of a fatty acid binding protein (FABP) in mammalian heart. This protein binds free fatty acids and their esters with high affinity, however, its physiological role remains unknown. Since FABP constitutes a significant amount of cystolic protein, it is likely that it would be a target for free radical attack. To test this hypothesis, FABP was examined for scavenging against free radicals such as the superoxide anion (O2-), hydroxyl radical (OH.) and hypochlorite radical (OCl.) which may be present in an ischemic reperfused heart. Our results suggest that FABP scavenges O2-, OH. and OCl. as indicated by the FABP inhibition of O2- -dependent reduction of cytochrome c, OH.-dependent hydroxybenzoic acid formation and OCl.-mediated chemiluminescence response. FABP was found to be a more potent scavenger of these free radicals compared to bovine serum albumin. Furthermore, FABP was more effective in scavenging OH. than O2-, and inhibited OH. mediated lipid peroxidation process. These results indicate that FABP can scavenge free radicals which may be present in an ischemic/reperfused heart and, thus, may play a significant physiological role in the heart during ischemia and reperfusion.
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PMID:Free radical scavenging by myocardial fatty acid binding protein. 255 51


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