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

In vivo EPR oximetry is a powerful minimally invasive method that allows the measurement of oxygen in tissues through the use of a paramagnetic probe. In the present study, we investigated new strategies for preparing biocompatible inks containing carbon black particles (Printex U), which could be used as oxygen sensors. The carbon black particles were dispersed in solutions of biocompatible polymers of carboxy methyl cellulose (CMC), hydroxypropyl methyl cellulose (HPMC) or polyvinyl pyrrolidone (PVP). A total of 12 polymers with different molecular weights were tested. A physico-chemical characterization of the inks was carried out to assess the sedimentation of the particles, the rheological behavior of these inks, and the relative diffusion of the inks. The preparations with CMC and PVP had the highest viscosity and stability. The presence of the polymers did not modify the calibration curves (EPR linewidth as a function of the pO2) of the carbon black. In vivo, the oxygen sensors were stable for at least one month in muscles as the EPR linewidth remained fully sensitive to induced ischemia or carbogen challenge. The calibration curve was not modified after this period of implantation. A first study of biocompatibility was carried out in vitro (hemolysis and cytotoxicity assay) and in vivo (histological examination). No sign of toxicity was observed using these inks. These preparations are good candidates for future in vivo studies including clinical trials.
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PMID:Development and evaluation of biocompatible inks for the local measurement of oxygen using in vivo EPR. 1536 29

The protective effects of sarpogrelate (SG), a 5-HT2A antagonist, were investigated in perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion. Changes in cellular levels of high phosphorous energy, NO and Ca2+ in the heart together with simultaneous recordings of left ventricular developed pressure (LVDP) were monitored using an nitric oxide (NO) electrode, fluorometry and 31P-NMR. The recovery of LVDP from ischemia by reperfusion was 30.1% in the control, while the treatment with SG (5 x 10(-7) M) in pre- and post-ischemia hearts produced a gradual increase to 73.1 and 53.6%, respectively. At the final stage of ischemia, the intracellular concentration of Ca2+ ([Ca2+]i) and release of NO increased with no twitching and remained at a high steady level. The addition of SG increased the transient NO signal (TNO) level at the end of ischemia compared with the control, but [Ca2+]i during ischemia decreased. Meanwhile, mitochondrial Ca2+ uptake on acidification or Ca2+ content changes of the perfusate was suppressed by pre-treatment with SG or the KATP channel opener diazoxide, but not the KATP channel blocker 5-HD. The myocardial NO elevated with 5-HT in normal Langendorff hearts was suppressed by the treatment with SG. Therefore, the existence of the 5HT2A receptor in a Langendorff heart was anticipated. By in vitro EPR, SG was found to directly quench the hydroxy radical. Thus, these findings suggested that the 5-HT2A receptor induced in ischemia-reperfusion plays an important role in the mitochondrial KATP channel of hearts in close relation with NO and active oxygen radicals.
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PMID:Protective effects of sarpogrelate, a 5-HT2A antagonist, against postischemic myocardial dysfunction in guinea-pig hearts. 1601 Sep 79

Iron overload aggravates tissue damage caused by ischemia and ethanol intoxication. The underlying mechanisms of this phenomenon are not yet clear. To clarify these mechanisms we followed free iron ("loosely" bound redox-active iron) concentration in livers from rats subjected to experimental iron overload, acute ethanol intoxication, and ex vivo warm ischemia. The levels of free iron in non-homogenized liver tissues, liver homogenates, and hepatocyte cultures were analyzed by means of EPR spectroscopy. Ischemia gradually increased the levels of endogenous free iron in liver tissues and in liver homogenates. The increase was accompanied by the accumulation of lipid peroxidation products. Iron overload alone, known to increase significantly the total tissue iron, did not affect either free iron levels or lipid peroxidation. Homogenization of iron-loaded livers, however, resulted in the release of a significant portion of free iron from endogenous depositories. Acute ethanol intoxication increased free iron levels in liver tissue and diminished the portion of free iron releasing during homogenization. Similarly to liver tissue, the primary hepatocyte culture loaded with iron in vitro released significantly more free iron during homogenization compared to non iron-loaded hepatocyte culture. Analyzing three possible sources of free iron release under these experimental conditions in liver cells, namely ferritin, intracellular transferrin-receptor complex and heme oxygenase, we suggest that redox active free iron is released from ferritin under ischemic conditions whereas ethanol and homogenization facilitate the release of iron from endosomes containing transferrin-receptor complexes.
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PMID:Combination of iron overload plus ethanol and ischemia alone give rise to the same endogenous free iron pool. 1638 96

Nitrite (NO(2)-), being a product of metabolism of both nitric oxide (NO(*)) and nitrate (NO(3)-), can accumulate in tissues and regenerate NO() by several mechanisms. The effect of NO(2)- on ischemia/reperfusion injury was also reported. Nevertheless, the mechanisms of intracellular NO(2)- accumulation are poorly understood. We suggested significant role of nitrite penetration through biological membranes in the form of undissociated nitrous acid (HNO(2)). This hypothesis has been tested using large unilamellar phosphatidylcholine liposomes and several spectroscopic techniques. HNO(2) transport across the phospholipid bilayer of liposomes facilitates proton transfer resulting in intraliposomal acidification, which was measured using pH-sensitive probes. NO(2)(-)-mediated intraliposomal acidification was confirmed by EPR spectroscopy using membrane-impermeable pH-sensitive nitroxide, AMC (2,2,5,5-tetramethyl-1-yloxy-2,5-dihydro-1H-imidazol-3-ium-4-yl)-aminomethanesulfonic acid (pK 5.25), and by (31)P NMR spectroscopy using inorganic phosphate (pK 6.9). Nitrite accumulates inside liposomes in concentration exceeding its concentration in the bulk solution, when initial transmembrane pH gradient (alkaline inside) is applied. Intraliposomal accumulation of NO(2)- was observed by direct measurement using chemiluminescence technique. Perfusion of isolated rat hearts with buffer containing 4 microM NO(2)- was performed. The nitrite concentrations in the effluent and in the tissue, measured after 1 min perfusion, were close, supporting fast penetration of the nitrite through the tissue. Measurements of the nitrite/nitrate showed that total concentration of NO(x) in myocardium increased from initial 7.8 to 24.7 microM after nitrite perfusion. Physiological significance of passive transmembrane transport of NO(2)- and its coupling with intraliposomal acidification are discussed.
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PMID:Magnetic resonance study of the transmembrane nitrite diffusion. 1730 75

1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 6-(5-phenyl-3-pyrazolyloxy)hexyl ester (CV159) exhibits selective blocking of Ca(2+)/calmodulin and inhibits Ca(2+) overloading in living organisms. The effects of this antagonist in mice with hepatic ischemia-reperfusion injury were investigated using electron paramagnetic resonance imaging (EPRI) and ex vivo EPR (x-band EPR) techniques. The EPRI determined that the 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl half-life in CV159-treated mice was significantly shorter than that in untreated mice and was almost equal to that in the sham group. Both the cytosolic and the mitochondrial superoxide scavenging activities in CV-treated mice were significantly higher than that in untreated mice. Faint staining of the anti-superoxide dismutase antibody and strong staining of anti-inducible nitric oxide synthase antibody were observed in the liver of control group. In contrast to these findings, immunostaining of these antibodies in the liver of CV159-treated mice were reversed compared to control group. Western blotting showed that CV159 contributed to the high superoxide dismutase expression and low expression of inducible nitric oxide synthase. The alanine aminotransferase level in CV159-treated mice significantly decreased in comparison to that observed in the untreated mice. We conclude that CV159 retains its organ-reducing activity against radicals in hepatic reperfusion injury, which is mediated by the inhibition of Ca(2+) overloading.
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PMID:Effect of CV159-Ca(2+)/calmodulin blockade on redox status hepatic ischemia-reperfusion injury in mice evaluated by a newly developed in vivo EPR imaging technique. 1806 26

The beneficial action of dinitrosyl iron complex with glutathione on conjunctive veins of eyes in rabbits with experimental thrombosis of conjunctive veins has been demonstrated. Aqueous solutions of dinitrosyl iron complexes were added subconjunctively at doses of 5.4-8.1 micromole per eye. The average duration of thrombosis by the action of dinitrosyl iron complex decreased from 6.4 days in control animals to 2 days. The addition of dinitrosyl iron complex resulted in blood flow recovery in occlusive vessels and prevented ischemia and necrosis of tissues. The enhancement of hemorrhagic activity induced by dinitrosyl iron complexes was abrogated with combined addition of the nonselective NO synthase inhibitor N-nitro-L-arginine. In contrast, S-nitrosoglutathione affected adversely the veins: the duration of thrombosis in experimental thrombosis of conjunctive veins increased to 7 days. Intensive hemorhage developed in the conjunctive. The formation of protein-bound dinitrosyl iron complexes was observed by the EPR method in eye tissues after the subconjunctive or parabulbar addition of dinitrosyl iron complex with glutathione. This was not the case when the complex was injected intravenously. It was shown that dinitrosyl iron complex with glutathione induces the blockade of pellet aggregation or strengthens the fibrinolytic activity of plasma of patients with eye vessel pathology. The beneficial action of dinitrosyl iron complexes on conjunctive veins was proposed to be due to the capacity of dinitrosyl iron complexes to donate NO primarily to its biological targets. The release of free NO molecules in large amounts is not characteristic for dinitrosyl iron complexes. This process is characteristic of S-nitrosoglutathione, which sharply increases the probability of the accumulation of peroxynitrite, which produces a toxic effect on cells and tissues.
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PMID:[Effect of exogenous donors of nitric oxide and inhibitors of its enzymatic synthesis on experimental ischemic thrombosis in conjunctive veins of the rabbit eyes]. 1854 74

Chronic hyperglycaemia (60 days) which developed after streptozotocine (STZ) administration (5 mg/100 g) in rats was accompanied with development of severe endothelial dysfunction as well as with disturbed non-haem iron metabolism. It was established by EPR spectroscopy method that STZ administration reduced transferrin levels in the blood as well as pools of iron associated with blood transferrin and with ferritin in the heart and aorta of rats with hyperglycaemia. Chronic ecdysterone administration (100 ng/100 g, 60 days) protects hyperglycaemia development by preventing of non-haem iron metabolism disturbance. These data suppose participation of non-haem iron in mechanisms of ecdysterone protection of streptozotocine-induced hyperglycaemia and ischemia.
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PMID:[Role of non-haem iron in protecting effect of ecdysterone on development of streptozocin-induced hyperglycaemia in rats]. 1871 26

Changes in nitric oxide concentration in rat myocardium in vivo during temporary occlusion of the anterior descending coronary artery, followed by reperfusion were studied by microdialysis assay in risk and intact areas by using an NO spin trap (complex of ferrous ions with N-methyl-D, L-glucamine dihiocarbamate, Fe3+-MGD2). The amplitude of the EPR signal of the NO spin adduct NO-Fe2+-MGD2 in the risk area increased during the 40-min occlusion and remained higher than the initial level during 60-min postischemic reperfusion, indicating a substantial nitric oxide production. The size of the infarction in the risk area by the end of reperfusion was 47 +/- 3 %, the contents of ATP, phosphocreatine, and total creatine decreased to 44 +/- 4, 51 +/- 5, and 60 +/- 3 %, correspondingly, as compared with initial values, and the level of lactate was six times higher than the initial one. In the intact area of the left ventricle, the level of nitric oxide and high-energy metabolites did not change throughout the experiment. It was shown that the intensive nitric oxide production, in acute regional ischemia and reperfusion are related to the disturbance of energy metabolism, the damage to cytoplasmic membranes, and the death of cardiomyocytes.
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PMID:[The relationship between the production of nitric oxide and the injury of cardiomyocytes caused by in vivo rat regional myocardial ischemia and reperfusion]. 1881 87

Various mechanisms have been proposed to account for chemotherapy related ischemia, but none of them can explain the available clinical data. In order to explore the possibility that the decreased ability of erythrocytes to deliver oxygen to the heart could be responsible for cardiotoxicity, we have performed an ex vivo and in vivo study of the effects of cisplatin/5-FU on erythrocytes, using a variety of biophysical techniques. Combining EPR and microscopy it was concluded that both cardiotoxic 5-FU and non-cardiotoxic cisplatin have similar effects on the erythrocyte membrane, thus eliminating those changes as a potential source of cardiotoxicity. On the contrary, 31P-NMR and polarography showed that the effects of these cytostatics on the intracellular milieu differ significantly. 5-FU provoked a pronounced decrease of the O2 level in blood and affected the metabolism of phosphate compounds, while cisplatin had no such effects. When combined these two drugs showed synergistic effects, which matches the higher frequency of cardiotoxicity of the combination relative to the sole application of 5-FU. Preliminary results acquired on blood of patients receiving cisplatin/5-FU therapy verified observations obtained ex vivo. These results open a possibility of applying NMR in preclinical trials of new drugs in order to predict their ischemic potential.
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PMID:Decreased oxygen transfer capacity of erythrocytes as a cause of 5-fluorouracil related ischemia. 1912 37

This article reports the development and evaluation of two nano-emulsions (F45T-03/HFB and F15T-03/PFOB) containing fluorinated trityl radicals dissolved in perfluorocarbons. Preparation with a high-pressure homogenizer conferred sub-micronic size to both nano-emulsions. In vitro and in vivo EPR spectroscopy showed that the nano-emulsions had much greater oxygen sensitivity than the hydrophilic trityl, CT-03. In vivo experiments in rodents confirmed the ability of the nano-emulsions to follow the changes in oxygen concentration after induced ischemia. Histological evaluation of the tissue injected with the nano-emulsions revealed some acute toxicity for the F45T-03/HFB nano-emulsion but none for the F15T-03/PFOB nano-emulsion. These new formulations should be considered for further EPR oximetry experiments in pathophysiological situations where subtle changes in tissue oxygenation are expected.
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PMID:Nano-emulsions of fluorinated trityl radicals as sensors for EPR oximetry. 1912 93


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