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

The aim of this study was to evaluate the muscular regenerative properties after an induced ischemia/reperfusion injury of 4 hours and 30 min. of the left hind limb of the rat and to evaluate and compare the efficacy of native and modified polyethylene glycol superoxide dismutase (SOD and mPEG-SOD). In particular, we try to find a suitable method to study the histological and histoenzymatic properties of muscular fibres, focusing also the technical procedure employed to evaluate the new activated motor end-plates. Biopsies from flexor digitorum superficialis were collected immediately after the ischemia/reperfusion damage and also at 4th, 6th and 10th days. The adopted protocol showed a good reliability both for the necrosis and the regenerative process evaluations. However the assessment of regenerative and reinnervative processes will be completed by histomorphometric analysis.
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PMID:Preliminary histoenzymatic muscular evaluations after ischemia-reperfusion damage. 851 89

The protective effect of oxygen free radical scavenger superoxide dismutase (SOD) against the warm ischemic damage that occurs in kidneys harvested from non-heart-beating donors is controversial because of its short half-life. In this model, we compared the protective effect of SOD and two longer lasting polyethylene glycol (PEG)-linked forms of SOD in a model of renal ischemia induced by 60 min of arterial clamping in rats. Rats treated with PEG1-SOD and PEG2-SOD had a better renal function than controls, with significantly lower serum creatinine levels throughout the follow-up period and a significantly higher creatinine clearance on postoperative days 1, 2, and 4. In native SOD treated-rats, serum creatinine was lower than in controls, though not significantly so, and creatinine clearance was significantly higher on postoperative day 4. Our results indicate that the protective effect of SOD against renal warm ischemia can be enhanced by prolonging its half-life by binding the enzyme to PEG.
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PMID:Protective effect of superoxide dismutase and polyethylene glycol-linked superoxide dismutase against renal warm ischemia/reperfusion injury. 893 60

Tumor necrosis factor alpha (TNF-alpha) is expressed in the ischemic brain; however, its precise role is not fully understood. We studied the effect of the dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp) on focal cerebral ischemia in mice using a permanent middle cerebral arterial occlusion (MCAO) model. TNFbp was applied topically, intravenously, or intraperitoneally. TNFbp binds and inhibits TNF-alpha. The volume of cortical ischemic lesions was measured by means of 2,3,5-triphenyltetrazolium chloride 24 h after MCAO. TNFbp produced a significant reduction in the cortical infarct volume of vehicle-treated animals (p < 0.001). The reduction in the volume of brain damage was 26% in animals that received 3 mg/kg of TNFbp topically. Further analysis of TNF-alpha inhibition following acute brain ischemia is indicated.
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PMID:Inhibition of tumor necrosis factor and amelioration of brain infarction in mice. 904 May 3

Although the pathogenesis of necrotizing enterocolitis remains uncertain, ischemia appears to be an important contributing factor to the development of this disorder. Reperfusion plays a major role in ischemia-related injury, and oxygen free radicals produced during reperfusion most likely contribute to the injury. These oxidants can be generated during prostanoid metabolism, which increases during reperfusion of ischemic gut in adult subjects. The present study was designed to: 1) examine the effects of superior mesenteric artery occlusion, e.g. ischemia and reperfusion in vivo on the development of histopathologic intestinal injury; 2) determine whether products of arachidonic acid metabolism, e.g. prostanoids are increased during reperfusion of ischemic gut; and 3) determine whether oxygen free radical scavengers attenuate the injury in newborn pigs. Chronically catheterized placebo-pretreated newborn pigs exposed to ischemia-reperfusion, placebo-pretreated nonischemic control pigs, and polyethylene glycol-superoxide dismutase (SOD) plus polyethylene glycol-catalase (CAT)-pretreated, ischemic pigs were studied by examining changes in intestinal circulation, oxygenation, prostanoids, and tissue injury. In the placebo-pretreated pigs, intestinal blood flow decreased to very low levels during superior mesenteric artery occlusion. During reperfusion, blood flow increased, but remained below baseline. After ischemia, oxygen uptake returned to values that were similar to baseline. Intestinal efflux of the vasodilator 6-keto-prostaglandin F1alpha was evident (p < 0.05 versus no or zero efflux) during early reperfusion. Histopathologic scoring of terminal ileal samples showed significant mucosal necrosis, surface epithelial disruption, lamina propria congestion and hemorrhage, submucosal hemorrhage, edema, and increases in cells compared with the placebo-pretreated nonischemic pigs. In the SOD plus CAT-pretreated ischemic pigs, changes in intestinal blood flow, oxygen uptake, 6-keto-prostaglandin F1alpha efflux, and the pattern of the ileal tissue injury did not differ significantly from the placebo-pretreated ischemic pigs. In summary, superior mesenteric artery occlusion for 1 h and reperfusion for 2 h resulted in severe intestinal ischemia, early postocclusive limited increases in intestinal perfusion and oxygen uptake, efflux of vasodilating prostanoids during early reperfusion, and signs of ischemic tissue injury in the placebo- and SOD plus CAT-pretreated pigs. This study demonstrates that, after superior mesenteric artery occlusion and reperfusion, severe intestinal tissue injury is detected in vivo, prostanoid efflux increases, and SOD plus CAT given just before occlusion does not attenuate the extent of injury in newborn pigs.
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PMID:Ischemia-reperfusion injury in the intestines of newborn pigs. 926 20

Electron paramagnetic resonance (EPR) spectroscopy was used to directly measure free radical generation in ischemic/reperfused diabetic rat retina. Tissue was frozen at 77 degrees K after 90 min ischemia, and 90 min ischemia followed by 1 min, 3 min, 5 min, and 24 hours reperfusion, respectively. After 90 min of ischemia followed by 1 min, 3 min, 5 min, and 24 hours of reperfusion (n = 10 in each group), free radical signal intensity was increased from its diabetic nonischemic control value of 12 +/- 3 arbitrary units to 58 +/- 6 (P < 0.05), 62 +/- 7 (P < 0.05), 32 +/- 5 (P < 0.05), and 14 +/- 4 arbitrary units, respectively. The peak intensity of free radical production was observed after 90 min ischemia followed by 3 min of reperfusion; therefore, this time point was selected to study the retinal free radical production in superoxide dismutase (conjugated with polyethylene glycol, PEG-SOD) and EGb 761 (Ginkgo biloba extract)-treated groups. With 7,500, 15,000, and 30,000 U/liter of SOD, and 25, 50, and 100 mg/kg of EGb 761, a dose-dependent reduction in oxygen free radical production was detected, respectively, which may be responsible for the attenuation of abnormal postischemic function in ischemic and reperfused diabetic retina.
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PMID:Direct measurement of free radicals in ischemic/reperfused diabetic rat retina. 929 50

Compound resting membrane potential was recorded by the grease gap technique (37 degrees C) during glycolytic inhibition and chemical anoxia in myelinated axons of rat optic nerve. The average potential recorded under control conditions (no inhibitors) was -47 +/- 3 (SD) mV and was stable for 2-3 h. Zero glucose (replacement with sucrose) depolarized the nerve in a monotonic fashion to 55 +/- 10% of control after 60 min. In contrast, glycolytic inhibition with deoxyglucose (10 mM, glucose omitted) or iodoacetate (1 mM) evoked a characteristic voltage trajectory consisting of four distinct phases. A distinct early hyperpolarizing response (phase 1) was followed by a rapid depolarization (phase 2). Phase 2 was interrupted by a second late hyperpolarizing response (phase 3), which led to an abrupt reduction in the rate of potential change, causing nerves to then depolarize gradually (phase 4) to 75 +/- 9% and 55 +/- 6% of control after 60 min, in deoxyglucose and iodoacetate, respectively. Pyruvate (10 mM) completely prevented iodoacetate-induced depolarization. Effects of glycolytic inhibitors were delayed by 20-30 min, possibly due to continued, temporary oxidative phosphorylation using alternate substrates through the tricarboxylic acid cycle. Chemical anoxia (CN- 2 mM) immediately depolarized nerves, and phase 1 was never observed. However a small inflection in the voltage trajectory was typical after approximately 10 min. This was followed by a slow depolarization to 34 +/- 4% of control resting potential after 60 min of CN-. Addition of ouabain (1 mM) to CN--treated nerves caused an additional depolarization, indicating a minor glycolytic contribution to the Na+-K+-ATPase, which is fueled preferentially by ATP derived from oxidative phosphorylation. Phases 1 and 3 during iodoacetate exposure were diminished under nominally zero Ca2+ conditions and abolished with the addition of the Ca2+ chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA; 5 mM). Tetraethylammonium chloride (20 mM) also reduced phase 1 and eliminated phase 3. The inflection observed with CN- was eliminated during exposure to zero-Ca2+/EGTA. A Ca2+-activated K+ conductance may be responsible for the observed hyperpolarizing inflections. Block of Na+ channels with tetrodotoxin (TTX; 1 microM) or replacement of Na+ with the impermeant cation choline significantly reduced depolarization during glycolytic inhibition with iodoacetate or chemical anoxia. The potential-sparing effects of TTX were less than those of choline-substituted perfusate, suggesting additional, TTX-insensitive Na+ influx pathways in metabolically compromised axons. The local anesthetics, procaine (1 mM) and QX-314 (300 microM), had similar effects to TTX. Taken together, the rate and extent of depolarization of metabolically compromised axons is dependent on external Na+. The Ca2+-dependent hyperpolarizing phases and reduction in rate of depolarization at later times may reflect intrinsic mechanisms designed to limit axonal injury during anoxia/ischemia.
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PMID:Ion transport and membrane potential in CNS myelinated axons. II. Effects of metabolic inhibition. 932 77

The objective of this study was to test the hypothesis that treatment with the calcium antagonist felodipine in normal clinical dosages may have a myocardio-protective effect in the event of ischemia followed by reperfusion. Comparing the cardioprotective effects of felodipine and an agent of another class allowed the influence of blood pressure reduction per se to be evaluated. Twenty open-chest pigs were exposed to 45 minutes of myocardial ischemia via occlusion of the left anterior descending coronary artery (LAD) followed by 240 minutes of reperfusion. Either felodipine (felo group; n = 7) or sodium nitroprusside (SNP group; n = 7) was administered intravenously starting at 180 minutes before the LAD occlusion in a dose that was intended to reduce the mean arterial blood pressure (MAP) by 30%. Six pigs (vehicle group) serving as controls received a mixture of polyethylene glycol (PEG) and 5% glucose, the vehicles for felodipine and SNP, intravenously. MAP in the felo and SNP groups was reduced to 65% and 72% of the preinfusion levels, respectively. Infarct size as a percentage of the area at risk was 49% in the felo, 73% (P < 0.05) in SNP, and 79% (P < 0.01) in the vehicle groups, respectively. Felodipine, given in a dose resulting in plasma levels corresponding to the therapeutic range in patients on antihypertensive treatment, reduced infarct size following myocardial ischemia/reperfusion. Afterload reduction induced by nitroprusside did not influence infarct size. Thus, felodipine exerted a myocardioprotective effect unrelated to the mechanism of afterload reduction in clinically relevant antihypertensive dosages.
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PMID:Myocardioprotective effects of felodipine in an antihypertensive dosage: an experimental study in pigs. 960 31

By means of a simplified questionnaire, the NADYA group has gathered and analyzed data with regard to the age, sex, diagnosis, access route, duration, form of administration, complications, and quality of life, in 812 patients (62% male; 37% female) with At Home Enteral Nutrition (AHEN), and 19 patients (42% male; 57% female) with At Home Parenteral Nutrition (AHPN) corresponding the National Registry of 1995. The most frequent indication of AHEN was a neoplasm (41%), followed by neurological alterations (33%). The most common access route is the NGT (37%) followed by oral administration in 37%, PEG in 13% and surgical ostomics in 8%. The mean treatment time is 8 months. The index of complications/patient-year is 0.50 (gasterointestinal 0.17, and mechanical alterations 0.9). At the end of the study, 63% of the patients continued to receive AHEN, showing a mortality rate of 70%. The majority of the patients undergoing treatment presented a sever social disability (20%) or were bed ridden (18%). The most common indications for the AHPN are: radical enteritis (26%), Crohn's disease (21%), and mesenteric ischemia (16%). AIDS, motility alterations, and neoplasic diseases are scantly represented (10%). Tunneled catheters are used in 58% of the cases, and Port-a-Cath in 31%). The mean duration for the treatment was 7.9 months. An index of 0.47 hospitalization/patient-year was seen in relation to the nutritional treatment (mainly due to catheter septicemia). A mortality of 16% is noted, and 21% show a recovery of the oral route. 42% of the patients did not present an assessable social disability.
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PMID:[Artificial nutrition in the home. 1995 yearly report. NADYA-SENPE Group (Natiional Registry of Patient-Spanish Society for Parnteral and Enterlal Nutrition]. 966 56

Diffusion in the extracellular space (ECS) is important in physiologic and pathologic brain processes but remains poorly understood. To learn more about factors influencing tissue diffusion and the role of diffusion in solute-tissue interactions, particularly during cerebral ischemia, we have studied the kinetics of several radiotracers in control and hypoxic 450-microm hippocampal slices and in 1,050-microm thick slices that model the ischemic penumbra. Kinetics were analyzed by nonlinear least squares methods using models that combine extracellular diffusion with tissue compartments in series or in parallel. Studies with 14C-polyethylene glycol confirmed prior measurements of extracellular volume and that ECS shrinks during ischemia. Separating diffusion from transport also revealed large amounts of 45Ca that bind to or enter brain as well as demonstrating a small, irreversibly bound compartment during ischemia. The rapidity of 3H2O entry into cells made it impossible for us to distinguish intracellular from extracellular diffusion. The diffusion-compartment analysis of 3-O-methylglucose data appears to indicate that 5 mmol/L glucose is inadequate to support glycolysis fully in thick slices. Unexpectedly, the diffusion coefficient for all four tracers rose in thick slices compared with thin slices, suggesting that ECS becomes less tortuous in the penumbra.
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PMID:Diffusion of radiotracers in normal and ischemic brain slices. 966 8

Brain-derived neurotrophic factor (BDNF) is neuroprotective in the ischemic hippocampus if the neurotrophin is injected directly into the brain. However, the efficacy of BDNF via peripheral (i.v.) administration is limited by the lack of transport of the neurotrophin through the brain capillary wall, which makes up the blood-brain barrier (BBB) in vivo. The present studies describe a molecular reformulation of BDNF that incorporates polyethylene glycol (PEG) moieties at surface carboxyl residues, to optimize plasma pharmacokinetics, and links pegylated BDNF to the OX26 mAb, which undergoes receptor-mediated transport through the BBB via the brain capillary endothelial transferrin receptor. The BDNF-PEG 2000-biotin conjugated to OX26/streptavidin was administered i.v. daily to rats for 1 week after a 12-min period of transient forebrain ischemia. The neuronal density in the CA1 sector of the hippocampus was decreased 68 +/- 10% at 1 week after the ischemia. There was no neuroprotective effect of the unconjugated BDNF or unconjugated OX26 mAb. However, the hippocampal CA1 neuronal density was normalized by i.v. administration of the BDNF-PEG 2000-biotin conjugated to OX26/streptavidin. These studies demonstrate that peripherally administered BDNF may have neuroprotective effects in brain, if the neurotrophin is reformulated to (i) optimize plasma pharmacokinetics with carboxyl-directed pegylation, and (ii) enable transport through the BBB by coupling to brain transport vectors.
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PMID:Neuroprotection with noninvasive neurotrophin delivery to the brain. 987 5


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