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

Results of our consecutive study on the pathogenic mechanism underlying ischemic brain edema are summarized in this paper. Pertinent findings are as follows: (1) there is a close correlation between the influxes of water and sodium following ischemia; (2) the edema fluid can be regarded as the ultrafiltrate of serum; (3) there is a significant increase in the brain content of HETEs following ischemia; (4) the lipoxygenase activity of brain microvessels is increased following ischemia; (5) the lipoxygenase activity as well as the Na+, K+-ATPase activity of brain microvessels are enhanced by a hydroperoxide, 15-HPETE; (6) inhibition of Na+, K+-ATPase of brain microvessels by intraarterial infusion of ouabain resulted in a significant decrease in edema formation; and (7) not the cyclooxygenase, but the lipoxygenase pathway seems to be involved in the enhancement of microvessel Na+, K+-ATPase. Lipoxygenase(s) and Na+-K+-ATPase of brain microvessels, the activities of which are enhanced by an increased level of free radicals and/or hydroperoxides, may play a significant role in the occurrence of ischemic brain edema.
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PMID:The role of free radicals and eicosanoids in the pathogenetic mechanism underlying ischemic brain edema. 266 83

The results of our experiments demonstrated that one hour of ischemia followed by one hour of reflow in the kidney caused a reduction in (Na+K+)ATPase activity and microsomal sulfhydryl content as well as an increase in microsomal lipid peroxidation. Renal venous malondialdehyde concentration was increased soon after reperfusion of the ischemic kidney. All these changes were rectified by an infusion of 0.123 mmol N-(2-mercaptopropionyl)glycine/kg over a 70 min period. On the other hand, an in vitro addition of 0.01-0.5 mM N-(2-mercaptopropionyl)glycine to a membrane preparation in the presence of H2O2 and Fe3+ did not prevent but rather potentiated the free radical effect on the enzyme activity. However, addition of superoxide dismutase alone or with catalase together with 2-MPG were effective in preventing the enzyme depression induced by H2O2. The results therefore indicate that free radical generation participates in the evolution of ischemia/reperfusion cell injury and thiol-reducing agents may be beneficial in alleviating the cell damage in vivo.
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PMID:Effects of N-(2-mercaptopropionyl)glycine on ischemic-reperfused dog kidney in vivo and membrane preparation in vitro. 283 50

A partially purified, membrane-bound Na+-K+-ATPase fraction, prepared from the outer medulla of porcine kidney, was incubated in the presence of 0.1 mM FeCl3, 1 mM ADP, and 0.1-100 mM H2O2 for either 15 or 30 min at 37 degrees C. The activity of ouabain-sensitive Na+-K+-ATPase was reduced proportionally to the concentration of H2O2 and the duration of incubation. There were decreases in SH contents and turnover rates of the Na+-K+-ATPase preparation, while malondialdehyde (MDA) and conjugated dienes were generated from the membrane lipids in the course of the incubation. The concentrations of ethanolamine (E) plasmalogen and of arachidonic acid in the E glycerophospholipid molecules were reduced by the free radical reaction. Similarly, a reduction in Na+-K+-ATPase activity and the formation of MDA and conjugated dienes, together with a decrease in E glycerophospholipids, were observed when the membrane fraction was exposed to ultraviolet irradiation (254 nm) for 30 min at 4 degrees C. Administration of 10 mM dithiothreitol alleviated the reductions in enzyme activity, in turnover rate, and in SH content without suppressing MDA formation. Addition of 2 mM butylated hydroxytoluene to the incubation mixture prevented the lipid peroxidation without totally normalizing the enzyme activity in the H2O2 experiment, whereas this antioxidant restored the ATPase activity to normal in the ultraviolet experiment. Microsomal fractions, prepared from the outer medulla of canine kidney after 1 h of unilateral ischemia and 1 h of reperfusion, showed a decreased Na+-K+-ATPase activity, a reduced amount of SH groups, and an increased MDA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Depression of membrane-bound Na+-K+-ATPase activity induced by free radicals and by ischemia of kidney. 283 28

The present study was initiated to determine whether pretreatment of gerbils with calcium channel blockers, flunarizine and verapamil would prevent injury to cerebral ATPases following secondary ischemia consisting of 60-min bilateral clamping of the carotids followed by 40 min of reperfusion. The sequence of ischemia produced a deficit in Na+,K+-ATPase activity without influencing Ca++,Mg++- or Mn++-sensitive ATPases. Pretreatment with flunarizine significantly prevented the damage to Na+,K+-ATPase while the effect of verapamil was marginal. Verapamil, along with dimethylsulfoxide (DMSO), reduced the mortality rate of gerbils subjected to the paradigm of ischemia. When added directly to the cerebral fractions in vitro the two calcium channel blockers inhibited Na+,K+-ATPase alone. Flunarizine was more potent in vitro than verapamil.
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PMID:Protective action of calcium channel blockers on Na+,K+-ATPase in gerbil cerebral cortex following ischemia. 283 93

Global ischemia in guinea-pig hearts for 60 to 90 min depressed microsomal and mitochondrial Ca2+ uptake activities. Reperfusion of the 60 min ischemic hearts resulted in incomplete recovery of contractile function and calcium uptake activities of both mitochondrial and microsomal fractions. On the other hand, reperfusion of the 90 min ischemic hearts further depressed the microsomal Ca2+ uptake activity. Coronary occlusion for 90 min in dog hearts was found to decrease microsomal Ca2+-pump and sarcolemmal Na+-K+ ATPase activities. Reperfusion of these regional ischemic hearts further depressed the microsomal Ca2+ uptake and Ca2+-stimulated ATPase as well as sarcolemmal Na+-K+ ATPase activities whereas mitochondrial Ca2+ uptake was increased. Perfusion of rat hearts for 60 min with hypoxic medium resulted in depression of the sarcolemmal Na+-dependent Ca2+ uptake and ATP-dependent Ca2+ uptake activities. Reperfusion of these hypoxic hearts failed to recover the sarcolemmal Na+-Ca2+ exchange and Ca2+-pump activities. These results demonstrate that membrane defects with respect to Ca2+ transport processes in ischemic/hypoxic hearts may be associated with irreversible injury.
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PMID:Alterations in heart membrane calcium transport during the development of ischemia-reperfusion injury. 284 10

It has been proposed that oxygen free radical production is an important mediator of the myocardial dysfunction during the course of acute ischemia. We tested this hypothesis by characterizing the pathway of calcium efflux across sarcoplasmic reticulum (SR) membranes affected by oxygen free radicals. The effect of oxygen free radicals on the steady state calcium load, calcium permeability, and Ca,Mg-ATPase activity of isolated canine cardiac SR vesicles was investigated at pH 7.0. In vitro generation of oxygen free radicals by xanthine oxidase (0.09 units/ml), acting on xanthine in doses up to 50 microM as a substrate, increased the permeability of the SR vesicles to calcium, determined by measuring net efflux of calcium after stopping pump-mediated fluxes, and decreased total intravesicular calcium and free intravesicular calcium with no effect on Ca,Mg-ATPase activity. The effect of oxygen free radicals on calcium permeability was calcium gradient-dependent. Xanthine alone or xanthine plus denatured xanthine oxidase had no effect on this system. Superoxide dismutase (SOD, 56 units/ml), but not denatured SOD, significantly inhibited the effect of xanthine-xanthine oxidase reaction. The calcium permeability of the SR membrane decreased with decreasing calcium load. In addition, inasmuch as extravesicular calcium exerts only a slight effect on calcium permeability, the decrease in the permeability with calcium load is specifically related to the calcium load. Oxygen free radical-induced increase in calcium permeability was unaffected by Mg concentration between 2.1 and 21 mM. In summary, our data reveal that .O2- can produce a diminished level of accumulated calcium, which is reflected by the decreased calcium load and an increase in passive calcium permeability, and that the decreased calcium accumulation in the presence of the xanthine-xanthine oxidase system may not be mainly due to an inhibited calcium pump but due to an increased calcium permeability. Our results also suggest that increased SR membrane passive calcium permeability induced by oxygen free radicals is not carrier mediated. It is postulated that, with the oxygen free radical-mediated progressive increase in calcium permeability, free cytosolic calcium concentrations would increase in ischemic myocardium.
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PMID:The effect of oxygen free radicals on calcium permeability and calcium loading at steady state in cardiac sarcoplasmic reticulum. 284 52

Impairment of mitochondrial respiration in early myocardial ischemia was studied with special reference to myocellular irreversible injury. The technique used was total ligation of the left anterior descending coronary artery, followed by reconstruction of coronary blood flow, in the dog. State 3 respiratory activity reduced significantly to 76% of that of the non-ischemic myocardium in subendocardial muscle (Endo) as early as 30 min after occlusion, and at 60 min to 84% in the subepicardium (Epi). The activity was not recovered by reperfusion. The activity of complex I of sonicated submitochondrial particles decreased at 30 min to 67% in Endo and at 60 min to 71% in Epi, and was not recovered by reperfusion. Complex II and IV activities were kept in the control level until 60 min of ischemia. DNP-stimulated ATPase activity reduced to 79% in Endo at 15 min and to 70% in Epi at 30 min, but recovered significantly by reperfusion until 30 min of ischemia. Mitochondrial respiratory activity was impaired irreversibly in ischemia for 30 min in Endo and this spread to Epi later. Degradation of complex I is considered to be one of the causes of myocardial irreversibility in early ischemia.
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PMID:Impairment of mitochondrial respiratory activity in the early ischemic myocardium--with special reference to electron transport system. 284 64

An analysis of an electric scheme of hepatocyte under conditions of stopping and restoring the blood flow taking into account the morphological and biochemical characteristics of the normal and injured liver was carried out. It is shown that the fast phase of restoring the membrane potential (MP) when restoring the blood flow following ischemia is stipulated by restoring extracellular concentrations of potential-generating ions; and slow restoring of the normal liver MP is connected with the phase of potassium efflux hyperpolarization. The injured liver MP stability to ischemia is higher because of the transmembrane ion gradient decrease before ischemia and next effect of depolarisation of passive currents weakening under conditions of closed extracellular space, and total ATPase activity decrease, i.e. a more economical ATP expenditure by the cell at ischemia.
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PMID:[Analysis of an equivalent electric circuit of the hepatocyte during stopping and restoration of the blood flow]. 285 32

The present experiments were designed to determine the kinetic pattern of Na,K-ATPase in the presence of varying concentrations of Na+ and K+ ions in controls and gerbils exposed to 1 and 5 min of ischemia, respectively, and 60 min and 4 days of recirculation following 5 min of transient ischemia. The pattern of Na,K-ATPase activity in the control cerebral cortex and hippocampus is different. The cortical Na,K-ATPase apparently is more resistant in keeping an optimal activity than the enzyme in the hippocampus. After ischemic insult of either 1 or 5 min in duration, the enzyme activity is inhibited in both brain structures. 4 days after 5 min of ischemia, indicating greater flexibility of the cortical enzyme or less damage than in the hippocampus. Furthermore, the data obtained show that only through the enzyme behavior and kinetic parameters is it possible to reach conclusions about the enzyme function or dysfunction under pathological conditions.
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PMID:Alterations in synaptosomal membrane Na,K-ATPase of the gerbil cortex and hippocampus following reversible brain ischemia. 285 24

Marker enzyme activities of different subcellular fractions were analyzed in cortex homogenates from rat kidney after different periods (15, 30, 60, and 90 min) of warm ischemia. Lactate dehydrogenase, alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and succinate-cytochrome c reductase were not altered by ischemia in these periods. ATPase (2,4-dinitrophenol-stimulated and azide-sensitive), 5'-nucleotidase, K-Mg-nitrophenylphosphatase decline within 30 min of ischemia, whereas the microsomal enzymes glucose-6-phosphatase and NADPH-cytochrome c reductase decreased not before 60 min of ischemia. The early decrease of ATPase and of plasma membrane enzymes can be regarded as a consequence of membrane alterations. This enzymatic approach may be helpful to evaluate pharmacological agents for preventing and reserving ischemic effects in kidneys in a rational manner.
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PMID:Changed enzyme activities in rat kidney during ischemia. 286 6


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