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

Reperfusion of ischemic myocardium has been postulated to result in a specific oxygen radical-mediated component of tissue injury. In a previous study we demonstrated improved recovery of ventricular function and metabolism when the superoxide radical scavenger superoxide dismutase was administered at the time of postischemic reflow. Studies in vitro, have suggested that superoxide toxicity might be mediated via the generation of more reactive hydroxyl radicals in an iron-catalyzed reaction. The present study was designed to test the hypothesis that myocardial reperfusion injury might be reduced by administration of the iron chelator deferoxamine at the time of reflow, most likely by preventing hydroxyl radical formation. Sixteen isolated Langendorff rabbit hearts, perfused within the bore of a superconducting magnet, were subjected to 30 min of normothermic (37 degrees C) total global ischemia followed by 45 min of reperfusion. At reflow eight treated hearts received a 10 ml bolus containing 50 mumol of deferoxamine followed by an infusion of 11 mumol/min for the first 15 min of reflow. The hearts were then perfused with standard perfusate for an additional 30 min. Eight untreated control hearts received a similar bolus of perfusate followed by 45 min of standard reperfusion. Serial 5 min 31P nuclear magnetic resonance spectra were recorded. Myocardial phosphocreatine (PCr) content fell to 5% to 7% of control during ischemia in both groups of hearts. Deferoxamine-treated hearts recovered 99 +/- 10% of control PCr content, while untreated hearts recovered 60 +/- 16% (p less than .05). Intracellular pH fell to 5.9 during ischemia in both groups, before showing more rapid and complete recovery in treated hearts (p less than .01). Recovery of developed pressure reached 70 +/- 6% of control in treated hearts compared with 35 +/- 10% in untreated hearts (p less than .05). Iron content of the perfusate was 7 microM, and by electron paramagnetic resonance spectroscopy was in the form of Fe3+-EDTA complexes. In the effluent of treated hearts iron was in the form of Fe3+-deferoxamine chelates. In summary, administration of the iron chelator deferoxamine at the time of postischemic reflow results in greater recovery of myocardial function and energy metabolism, which supports the hypothesis that iron plays an important role in the pathogenesis of reperfusion injury.
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PMID:Improvement of postischemic myocardial function and metabolism induced by administration of deferoxamine at the time of reflow: the role of iron in the pathogenesis of reperfusion injury. 282 Jun 15

These studies addressed the question of the in vivo distribution of rat brain hexokinase (HK), and whether physiologically relevant changes in the glycolytic rate are accompanied by changes in the distribution of HK. Homogenates of fresh tissue showed only 11-15% of the overt (assayable without added detergent) HK to be soluble (found in high-speed centrifugation supernatant fractions) when homogenization was begun within 15-20 s of sacrifice. Freeze-blown rat brain tissue also was used, coupled with a new technique wherein it was homogenized as it thawed in a buffered sucrose solution containing 1 mM EDTA. In tissue sampled 15 min (anesthetized) or 60 min (waking) after ip Nembutal injection (40 mg/kg), 23% of the overt HK and 79% of the total lactate dehydrogenase were soluble. The average phosphocreatine content of these and similar homogenates had decreased only 23% from in vivo levels, while ATP had decreased by 65%, due to the combined effects of a high level of endogenous ATPase, chelation of Mg2+ by EDTA, and the greater stability of Mg-ATP2- relative to Mg-ADP1-. These data indicated that the tissue experienced, at most, the equivalent of 6 s of complete ischemia prior to the completion of homogenization. Synaptosomes derived from rat and chicken cerebra were incubated at 37 degrees C in a physiological salt solution containing 10 mM glucose. Addition of veratridine has been shown to stimulate glycolysis and oxidative phosphorylation two- to threefold (H. T. Kyriazi and R. E. Basford (1986) J. Neurochem., in press), but did not alter the HK distribution, as 21% was found in the supernatant fractions of both control and veratridine-stimulated synaptosomes treated with digitonin. These results indicate that in brain tissue, large net movements of HK on and off the outer mitochondrial membrane do not occur, and thus play no role in the regulation of glycolysis.
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PMID:An examination of the in vivo distribution of brain hexokinase between the cytosol and the outer mitochondrial membrane. 294 9

Spin trapping technique has been applied to the detection of free radicals generated in NADPH stimulated lipid peroxidation process in ischemic brain homogenate. Using male Wistar rats, complete cerebral ischemia for 30 min, 60 min or 120 min was produced by decapitation followed by preservation of the heads at 37 degrees C. Global cerebral ischemia of 30 min or 60 min duration was induced by occlusions of three vessels (bilateral common carotid and basilar artery) in the ventilated rats. In some animals, bilateral carotid occlusions were released for 30 min following 30 min of ischemia to study postischemic event. Two reaction mixtures containing of brain homogenate, NADPH, Fe-EDTA and spin trapping reagent, phenyl-t-buthylnitrone (PBN), were prepared from each brain sample--one to be incubated in air and the other to be incubated in nitrogen gas. After the incubation for 20 min at 37 degrees C, free radical adducts of PBN were measured by electron spin resonance (ESR). In preliminary experiments, no ESR signals were obtained from the reaction mixtures without the addition of NADPH and Fe-EDTA. And the dependence of ESR signal intensity upon the NADPH concentration was observed. The six-line signals (triplet of doublets), which hyperfine splitting constants were AN = 16.2-16.5 G and A beta H = 3.6-3.8 G, were obtained from both ischemic models. These signals were dependent upon the presence of oxygen in the reaction systems, as evidenced by the fact that the signal intensity obtained from aerobic incubation was consistently stronger than that obtained from anaerobic incubation in each brain sample.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Detection of free radicals generated in NADPH-dependent lipid peroxidation in ischemic brain homogenates--use of the spin trapping technic]. 300 94

The regional concentrations of nine radiochemicals were measured in rat brain after induction of cerebral ischemia to identify tracers concentrated by brain undergoing selective neuronal necrosis. Transient (30 minute) forebrain ischemia was produced in the rat; 24 hours after cerebral recirculation the radiochemicals were injected intravenously and allowed to circulate for 5 hours. The brain concentrations of the radiochemicals in dissected regions were determined by scintillation counting. Forebrain ischemia of this nature will produce extensive injury to striatal neurons but will spare the great majority of neocortical neurons at 24 hours. The regional concentrations of these radiochemicals varied considerably in both control and ischemic animals. In postischemic animals, 4 radionuclides (63Ni, 99TcO4, 22Na, and [3H]tetracycline) were concentrated in the irreversibly damaged striatum in amounts ranging from 1.4 to 2.4 times greater than in normal tissue. The concentrations of 65Zn, 59Fe, 32PO4, and 147Pm in postischemic brain were similar to or less than those in normal brain. The concentration of [14C]EDTA was increased in injured and uninjured brain of postischemic rats. Autoradiographic analysis of the distribution patterns of some of these ions in normal animals showed that 99TcO4, 22Na, 65Zn, and 59Fe were distributed more uniformly throughout the brain than were 32PO4, 63Ni, and 147Pm. At 24 or 48 hours after ischemia, 63Ni, 99TcO4, and 22Na were preferentially concentrated in the damaged striatum and hippocampus, whereas 65Zn, 59Fe, 32PO4, and 147Pm did not accumulate in irreversibly injured tissue. Of the radiochemicals tested to date, Ni, TcO4, and tetracycline may be useful for diagnosing ischemic brain injury in humans, using positron emission tomography.
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PMID:Uptake of radiolabeled ions in normal and ischemia-damaged brain. 301 76

To determine whether iron participates in free radical-mediated postischemic renal injury and lipid peroxidation, we examined the effects of removal of endogenous iron or provision of exogenous iron following renal ischemia, as well as the effects of renal ischemia and reperfusion on renal venous and urinary "free" iron. Rats underwent 60 minutes of renal ischemia and were studied after either 24 hours (inulin clearance) or 15 minutes (renal malondialdehyde content) of reperfusion. Infusion of the iron chelator deferoxamine (200 mg/kg/hr) during the first 60 minutes of reperfusion resulted in a marked improvement in renal function (inulin clearance: 879 +/- 154 vs. 314 +/- 74 microliter/min; P less than 0.025) and a reduction in lipid peroxidation (renal malondialdehyde: 0.449 +/- 0.06 vs. 0.698 +/- 0.08 mmol/mg prot; P less than 0.05) compared to control animals. Infusion of 50 mg/kg/hr deferoxamine also protected renal function after ischemia (inulin clearance: 624 +/- 116 vs. 285 +/- 90 microliter/min; P less than 0.05) and resulted in less histologic injury. Iron-saturated deferoxamine had no protective effect. Conversely, infusion of the iron complex EDTA-FeCl3 during reperfusion exacerbated postischemic renal dysfunction and lipid peroxidation. Following renal ischemia there was no detectable increase in "free" iron in arterial or renal venous plasma. However, urinary "free" iron increased 10- to 20-fold following reperfusion. Iron chelators which underwent filtration and gained access to this free iron in the urine (free deferoxamine or inulin-conjugated deferoxamine) provided protection, whereas a chelator confined to the vascular space (dextran-conjugated deferoxamine) did not.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of iron in postischemic renal injury in the rat. 314 49

Rheological disorders, such as blood hyperviscosity, red blood cell (RBC) hyperaggregation or hypodeformability, may be responsible for vascular complications in diabetes. As pointed out by many reports, flavonoids are known to act on RBC rheology in relation with venous thrombosis. These disorders were evaluated by viscometry in order to follow the hemorheological impact of a flavonoid (Daflon 500 mg). Hemorheological effects of Daflon 500 mg, 6 tablets per day for 28 days, were tested in 18 diabetic patients by viscometric measurements carried out on 2 ml blood sample withdrawn on EDTA. Measurements, before and after treatment, were compared with usual statistical tests. The following results were obtained: (1) a decrease of blood viscosity, more pronounced at low shear rate; (2) a better RBC disaggregability process under shear. Therefore, the main conclusion was that the hemorheological improvement, observed after Daflon 500 mg treatment, due to a decrease of RBC aggregation, can induce a decrease of blood flow resistance and a reduction in stasis and resulting ischemia.
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PMID:Hemorheological improvement after Daflon 500 mg treatment in diabetes. 318 53

A new luminescence procedure based on the creatine kinase reaction was developed for measuring creatine in plasma. The method is highly applicable to small animal work where the amount of blood volume is critical. Only 20 microliter of sample is necessary for creatine analysis. Deproteinizing the plasma sample with ethanol at room temperature is convenient. This extraction method is adaptable to a clinical setting. The ethanol used in the extraction is compatible with the luminescence method but precipitated enzymes in the NADH spectrophotometric method because of the greater sample volume needed for analysis. The creatine concentration is stable in plasma for at least 1 hr in a final anticoagulant concentration of 10 mM EDTA. The correlation between the new luminescence method with the established NADH spectrophotometric method was excellent (r = 0.99). The accuracy of the within-run precision is high, with a mean coefficient of variation, 2-3%. Plasma creatine levels could be an important indicator denoting early cellular damage and of potential prognostic value. Preliminary studies in human muscle ischemia and early shock in rabbits revealed a significant increase in plasma creatine levels. Further investigations are necessary to evaluate its clinical importance.
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PMID:Plasma creatine determination using a luminescence method. 339 6

We tested the hypothesis that cultured chick embryo ventricular cells grown in monolayer could be used to study calcium fluxes across the myocardial sarcolemmal membrane during simulated ischemia. A specially adapted anaerobic chamber allowed the exposure of heart cells to profound hypoxia (PO2 less than 1.5 Torr) for prolonged periods of time. Ca2+ flux studies were conducted in this chamber following hypoxia and substrate deprivation to simulate important components of myocardial ischemia. To prove we were measuring cellular rather than interstitial cation contents we conducted 51Cr-EDTA interstitial space marker washout studies and showed that our procedures were sufficient to remove at least 99.7% of the extracellular fluid. The addition of lanthanum (1 mM) to the wash solution reduced nonspecific 45Ca2+ binding to the polystyrene culture plates to less than 0.03% of applied counts, but did not alter 45Ca2+ uptake under normoxic conditions. Following 2 h of hypoxia and substrate deprivation the Ca2+ content of the rapidly exchangeable Ca2+ pool of cultured monocytes increased 282% compared to control values during normoxia. We conclude that cultured chick embryo ventricular cells grown in monolayer are suitable for investigation of cation fluxes during simulated ischemia. Under the conditions studied, lanthanum displaceable Ca2+ did not make a major contribution to Ca2+ influx. The system permitted clear resolution of alterations in Ca2+ flux kinetics under conditions of profound hypoxia.
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PMID:Calcium flux measurements during hypoxia in cultured heart cells. 359 83

Flocculent densities in the matrix of mitochondria have become quite important in cell pathology since, when prominent, they indicate irreversible cell injury. The morphology and chemical nature of these flocculent densities have been studied in Kidney after various periods of autolysis in vitro in whole tissue samples and in isolated mitochondria. After 30 to 60 min of ischemia, flocculent densities were seen only occasionally and they were most prominent in samples subjected to mechanical damage during isolation. However, in 2- and 4-h samples numerous densities were seen. The size of the densities increased with time, being about 1,400 A in diameter at 4 h. Densities were also seen in mitochondria isolated in medium containing EDTA. They were seen only in the mitochondrial matrix, and could occasionally be found in condensed mitochondria. Small densities were generally round but larger one varied in shape and often appeared as aggregates of smaller densities. Digestion of the densities from water-soluble glycol methacrylate embedded samples was successful with pronase, but neither acid nor lipid solvents were effective. calcium or inorganic phosphate content of isolated mitochondria did not show an increase parallel to the occurrence of flocculent densities. The results suggest that the densities consist predominantly of protein and are probably formed through denaturation of proteins of the mitochondrial matrix and/or the inner membrane.
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PMID:Studies on the pathogenesis of ischemic cell injury. VI. Mitochondrial flocculent densities in autolysis. 611 11

Cellular injury induced by reperfusion after myocardial ischemia is manifested by striking mitochondrial damage as well as other hallmarks such as contraction band necrosis. Calcium has been implicated as a mediator of irreversible cellular injury in several systems. To identify other potential mediators of the mitochondrial injury associated with reperfusion, interactions between inorganic phosphate, oxygen, and mitochondria harvested from rabbit hearts were evaluated in vitro. Mitochondria exhibited rapid inactivation of oxidative phosphorylation after preincubation at 25 degrees C when phosphate and oxygen were present. Inactivation was partially but not completely precluded by EDTA, EGTA, magnesium, diltiazem, or ruthenium red, results in concert with findings of others suggesting involvement of a deleterious influx of calcium into mitochondria; exogenous calcium enhanced inactivation. However, the present data indicate that inactivation is prevented by incubation of mitochondria in the absence of oxygen, and demonstrate for the first time that injury elicited by phosphate is dependent on oxygen at physiological concentrations either because calcium and/or phosphate influx is linked to aerobic metabolism or because oxygen exerts deleterious effects on mitochondria, which may render them particularly susceptible to calcium influx. Since intracellular inorganic phosphate concentration increases markedly with ischemia, reperfusion with oxygenated medium may paradoxically augment mitochondrial injury in this setting. Thus, in the presence of increased intracellular concentrations of calcium and phosphate induced by ischemia, subsequent reestablishment of physiological levels of intracellular oxygen tension may promote mitochondrial damage, which is known to increase with reperfusion.
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PMID:Oxygen at physiological concentrations. A potential, paradoxical mediator of reperfusion injury to mitochondria induced by phosphate. 620 Apr 99


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