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

The hydroxyl radical is one of the most damaging oxygen metabolites that are thought to be produced during ischemia and reperfusion of cardiac tissue. Therefore, we used the isolated, isovolumetric, buffer-perfused rat heart preparation of cardioplegic arrest to assess the effects of interventions targeted at inhibiting production of the hydroxyl radical by decreasing either the availability of one of its precursors (hydrogen peroxide) or that of the metal catalyst (ferric iron) involved in the radical formation. Sixty hearts were studied and, except for nonischemic controls, were subjected to 3 hr of hypothermic (15 degrees to 18 degrees C) cardioplegic arrest, followed by 45 min of reperfusion. The following interventions were tested: pretreatment with peroxidase, a scavenger of hydrogen peroxide, pretreatment with a combination of peroxidase and the iron chelator deferoxamine, pretreatment with peroxidase followed by supplementation of the cardioplegic solution with deferoxamine, and supplementation of the cardioplegic solution with deferoxamine without preischemic enzymatic treatment. Based on comparisons of postreperfusion pressure development, maximal ventricular dP/dt, left ventricular compliance, and coronary flow, deferoxamine-containing cardioplegic solution alone afforded the best myocardial protection. This may be due to the ability of deferoxamine to act both as an iron chelator and as a direct scavenger of superoxide anion, an activated oxygen species that participates in hydroxyl radical formation. This study confirms that an important component of the cardiac damage sustained during global ischemia and reperfusion may involve injury caused by the hydroxyl radical. Furthermore, our results point out the potential therapeutic usefulness of deferoxamine in the context of cardioplegic protection during open-heart procedures.
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PMID:Prevention of hydroxyl radical formation: a critical concept for improving cardioplegia. Protective effects of deferoxamine. 282 88

Electron spin resonance spectroscopy has recently been used by others to detect directly radical species in isolated perfused hearts. Sample processing prior to spectroscopy in this study involved pulverization of tissue, which can artifactually generate radical species. We assessed in isolated perfused hearts the influence of tissue pulverization on the identity of radical species detected by spectroscopy and then, using a processing technique less likely to induce artifacts, whether myocardial ischemia and reperfusion generate radical species. Rat and rabbit hearts (n = 8) were perfused aerobically for 10 min and freeze-clamped to -196 degrees C. Frozen tissue was processed at -196 degrees C for spectroscopic analysis by pulverization vs. chopping. Spectra of pulverized tissue consisted of three components: a semiquinone (g = 2.004), a lipid peroxy radical (g [ = 2.04 and g = 2.006), and a carbon-centered radical that is possibly a lipid radical (giso = 2.002 and AHzz approximately equal to 50 G). Chopped tissue consisted of a single component, a semiquinone (g = 2.004). Rat hearts (n = 8 per group) also underwent 10-min global no-flow normothermic ischemia followed by 5-60 sec of either aerobic or anaerobic reperfusion, with frozen tissue chopped prior to spectroscopy. Spectra of ischemic tissue consisted of an iron-sulfur center and a semiquinone. Aerobic reperfusion resulted in a spectrum similar to the control but with increased amplitude that peaked after 10-15 sec of reflow. Anaerobic reperfusion yielded a spectrum identical to that of ischemic tissue. We conclude that pulverization of frozen myocardial tissue arti-factually generates radical species. Using a nonpulverization technique for tissue processing, we found that myocardial ischemia and reperfusion produce radical species but that molecular oxygen is necessary for the burst of radical production during reflow.
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PMID:Myocardial ischemia and reperfusion: direct evidence for free radical generation by electron spin resonance spectroscopy. 283 54

This paper summarizes current knowledge on the biochemistry of oxygen toxicity in general and the ischemia-reoxygenation tissue injury in particular. The superoxide radical, hydrogen peroxide, and the hydroxyl radical in cells can be formed enzymically or nonenzymically. Primary effects of oxygen radicals result in lipid peroxidation, which is believed to be initiated by a perferryl radical. Secondary effects are believed to be due to a disturbance in cellular calcium homeostasis. Reactions and treatment potentials are highly complex and their effects on cells, tissues, and organism are difficult to predict. Treatment potentials include superoxide dismutase, catalase, calcium entry blockers, iron chelators, xanthine oxidase inhibitors, and agents to prevent leukocyte adhesion. Reoxygenation injury mechanisms during resuscitation from clinical death can be studied in animals by evaluating the effects of antireoxygenation injury therapies and by monitoring free radical reactions.
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PMID:Biochemistry of reoxygenation injury. 284 73

Superimposition of cardioplegic arrest on acute low-cardiac-output states, as may occur after failure of percutaneous transluminal coronary angioplasty requiring emergency surgery, is associated with an increased operative risk. This increased risk is possibly attributable to reperfusion, which, after sequential episodes of myocardial ischemia, exacerbates tissue injury mediated by oxygen free radicals. One of the most cytotoxic of these active oxygen species is the hydroxyl radical, which is formed from superoxide anion and hydrogen peroxide through an iron-catalyzed reaction. This study assesses the effects of peroxidase, a hydrogen-peroxide scavenger, and of deferoxamine, an iron chelator, in isolated working rat hearts subjected to 30 minutes of low-flow ischemia (75% reduction in coronary flow) followed by 2 hours of cardioplegic arrest at 15 degrees C and by 30 minutes of normothermic reperfusion. Three groups of hearts (n = 7) were studied. Two groups were pretreated with either peroxidase (10,000 units/l) or deferoxamine (0.03 mM) during the last 15 minutes of the low-flow ischemic period. The third group received no prearrest intervention and served as a control group. In addition to hemodynamic determination, high-energy phosphate content [adenosine 5'-triphosphate (ATP)] and intracellular pH were monitored serially by 31P nuclear magnetic resonance spectroscopy. The two pretreated groups had better recovery of ATP levels and aortic flow values than did the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardioplegic arrest superimposed on evolving myocardial ischemia. Improved recovery after inhibition of hydroxyl radical generation by peroxidase or deferoxamine. A 31P nuclear resonance study. 284 3

The electron transport chain of the mitochondria is highly sensitive to myocardial ischemia. As free oxygen radicals take part in the damage that occurred during ischemia, this study was undertaken to determine if allopurinol and deferrioxamine had any beneficial effect on mitochondrial function. Our results showed that perfusion with allopurinol did not improve the mitochondrial function, but that reperfusion with allopurinol and deferrioxamine had a beneficial effect. We came to the conclusion that xanthine oxidase, as a generator of superoxide anions, is of minor importance in comparison with the hydroxyl radicals, which are probably formed in the presence of iron in the cell.
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PMID:The effect of allopurinol and deferrioxamine on rat heart mitochondrial oxidative phosphorylation after normothermic ischemic cardiac arrest and of reperfusion. 285 63

To monitor free radical scavenging properties of drugs, the 'stable' radical 2,2,6,6-tetramethylpiperidino-1-oxyl (TEMPO) was used. The sydnonimine molsidomine (SIN-1) effectively reduced the ESR signal whereas the nitrate isosorbidemononitrate (ISMN) did not. Thiol reagents like 2-mercaptopropionylglycine (MPG) or glutathione (GSH) only were effective in the presence of Fe2+ or Fe3+. Protein-bound iron in hemoglobin proved about four times more effective in reducing ESR signal height by thiols. It is suggested that the decrease in thiol content adds to the lack in protein bound iron of hemoglobin to induce the burst of free radicals in hypoxia (ischemia) and reperfusion.
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PMID:Free radical scavenging drugs, assessed by ESR studies: influence of hemoglobin. 285 30

Ischemia was simulated in rat liver perfused by physiological solution. The concentration of free iron and lipid peroxidation (LPO) products was measured 1, 2, 3, 4 and 5 hours after ischemia onset. The ESR method was used to measure free iron concentration. The LPO intensity was evaluated by the TBA test and by optical density at 232 nm. The content of free iron in cytoplasm increased in the course of ischemia with an increase in the concentration of LPO products. The content of free iron in the membranes remained unchanged. It is supposed that activation of LPO in ischemia may be caused by the appearance in the cytoplasm of a large amount of free iron. This iron can be liberated from ferritin in conditions of low oxygen concentration.
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PMID:[Role of endogenous free iron in activating lipid peroxidation in ischemia]. 298 78

Recent reports in the literature suggest that iron plays an important role in free radical-mediated injury in biological systems. To assess the role of iron-catalyzed oxidant production in ischemia-reperfusion injury, we examined the influence of deferoxamine (an iron chelator) and apotransferrin (iron transporting protein) on the increased intestinal vascular permeability produced by 1 h of ischemia and reperfusion. Both agents were administered intravascularly as a constant infusion, beginning 5 min before reperfusion. Capillary osmotic reflection coefficients were derived from the relationship between lymph-to-plasma protein concentration ratio and lymph flow in the feline small bowel. Vascular permeability in control intestinal preparations was 0.08 +/- 0.005, however it increased significantly to 0.40 +/- 0.03 in preparations subjected to 1 h of ischemia and 30 min of reperfusion. Vascular permeability in the deferoxamine-(0.15 +/- 0.009) and apotransferrin- (0.17 +/- 0.002) treated animals were significantly lower (P less than 0.01) than in the untreated group. Treatment with iron-loaded deferoxamine or transferrin did not offer any protection against ischemic injury. These findings support the hypothesis that iron plays an important role in the formation of hydroxyl radicals after reperfusion of the ischemic bowel.
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PMID:A role for iron in oxidant-mediated ischemic injury to intestinal microvasculature. 303 18

This article provides a brief review of recent developments regarding the pathophysiology of ischemic brain damage, and offers hypotheses explaining the pathogenesis of selective neuronal vulnerability and of tissue infarction, respectively. It is suggested that selective neuronal vulnerability, observed after brief periods of ischemia and after hypoglycemic coma, qualifies as an excitotoxic lesion, which causes postsynaptic damage to neurons innervated by excitatory amino acids by enhancing calcium influx. However, ischemic damage often involves glial and vascular cells as well, and causes infarction. It is hypothesized that this type of brain damage is related to acidosis and that enhanced acidosis is detrimental because it accelerates delocalization of protein-bound iron, with an ensuing free-radical damage to membrane lipids and proteins.
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PMID:Mechanisms of ischemic brain damage. 304 96

In this lecture, evidence is presented to support the following hypothesis regarding the roles of xanthine oxidase-derived oxidants and granulocytes in ischemia-reperfusion-induced microvascular injury. During the ischemic period, ATP is catabolized to yield hypoxanthine. The hypoxic stress also triggers the conversion of NAD-reducing xanthine dehydrogenase to the oxygen radical-producing xanthine oxidase. During reperfusion, molecular oxygen is reintroduced into the tissue where it reacts with hypoxanthine and xanthine oxidase to produce a burst of superoxide anion and hydrogen peroxide. In the presence of iron, superoxide anion and hydrogen peroxide react via the Haber-Weiss reaction to form hydroxyl radicals. This highly reactive and cytotoxic radical then initiates lipid peroxidation of cell membrane components and the subsequent release of substances that attract, activate, and promote the adherence of granulocytes to microvascular endothelium. The adherent granulocytes then cause further endothelial cell injury via the release of superoxide and various proteases.
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PMID:Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. 305 26


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