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

Calcium dobesilate possesses antioxidant properties and protects against capillary permeability by reactive oxygen species in the rat peritoneal cavity, but whether a similar action can take place in the diabetic rat retina is unknown. We investigated the oral treatment of diabetic rats with calcium dobesilate on the prevention of free radical-mediated retinal injury induced by ischemia/reperfusion (90 min ischemia followed by 3 min and/or 24 h of reperfusion). Streptozotocin-induced diabetic rats were orally treated with 50 and 100 mg/kg of calcium dobesilate for 10 days (n=12 in each group). In the first series of studies, calcium dobesilate was found to significantly reduce the maldistribution of ion content in diabetic ischemic/reperfused rat retina. Thus, in diabetic rats treated with 100 mg/kg/day calcium dobesilate, ischemia/reperfusion provoked: (i) 27.5% increase in retinal Na(+) content compared to 51.8% in the vehicle-treated group (P<0.05), and (ii) 59.6% increase in retinal Ca(2+) content compared to 107.1% in vehicle-treated animals (P<0.05). In the second series of studies, calcium dobesilate was found to significantly protect diabetic rat retina against inhibition of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase activities by ischemia/reperfusion (54% and 41% reduction, respectively, with 100 mg/kg of calcium dobesilate) and also against changes in retinal ATP, reduced glutathione (GSH), and oxidized glutathione (GSSG) contents. In the third series of experiments, rats treated with 100 mg/kg of calcium dobesilate reduced the hydroxyl radical signal intensity to 41% (measured by electron paramagnetic resonance), induced by ischemia/reperfusion in diabetic rat retina. Finally, 100 mg/kg calcium dobesilate significantly reduced retinal edema (measured by the thickness of the inner plexiform layer) in diabetic rats. In conclusion, oral treatment with calcium dobesilate significantly protected diabetic rat retina against oxidative stress induced by ischemia/reperfusion. Whether the antioxidant properties of calcium dobesilate explain, at least in part, its beneficial therapeutic effects in diabetic retinopathy deserves further investigation.
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PMID:Antioxidant properties of calcium dobesilate in ischemic/reperfused diabetic rat retina. 1167 46

Myocardial oxidative stress during retrograde continuous blood cardioplegia (RCBC) was evaluated in 22 patients undergoing elective aortocoronary bypass surgery. The patients were divided into two groups: Group C (n=11) received cold RCBC, and Group W (n=11) received warm RCBC. Myocardial oxidative stress was assessed by measuring the release of oxidized glutathione (GSSG), malondialdehyde (MDA), and myeloperoxidase (MPO) in the coronary sinus plasma before aortic clamping, at 1, 5, and 10 minutes after unclamping. Both the hemodynamic recovery and the creatine kinase MB (CKMB) activity were measured perioperatively until 24 hours after unclamping. In Group C, a significant coronary sinus release of GSSG was found in the early reperfusion period in comparison to Group W. No significant difference in the release of MDA nor MPO was noted in the two groups. The recoveries in the left and right ventricular functions, and the peak CK-MB activity were similar in both groups. In conclusion, warm blood cardioplegia is thus considered to protect the myocardium from ischemia-reperfusion injury better than cold blood cardioplegia under retrograde continuous perfusion.
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PMID:Retrograde continuous warm blood cardioplegia reduces oxidative stress during coronary artery bypass grafting. 1191 40

Kupffer cell-derived oxidant stress is critical for reperfusion injury after no-flow ischemia. However, the importance of Kupffer cells as source of reactive oxygen formation is unclear in a hemorrhagic shock model. Therefore, we evaluated Kupffer cell activation after 60 or 120 min of hemorrhage and 90 min of resuscitation (HS/RS) in pentobarbital-anesthetized male Fischer rats. Plasma glutathione disulfide (GSSG) as indicator for a vascular oxidant stress showed no significant changes after HS/RS. Plasma ALT activities were only moderately increased (100-200 U/L). Kupffer cells isolated from postischemic livers did not generate more superoxide than cells from sham controls. In contrast, the 10-fold increase of plasma GSSG and the 9-fold higher spontaneous superoxide formation of Kupffer cells after 60 min of hepatic no-flow ischemia followed by 90 min of reperfusion demonstrated the activation of Kupffer cells in this experimental model. Plasma ALT activities (1930 +/- 240 U/L) indicated severe liver injury. These results demonstrate a fundamental difference in the degree of Kupffer cell activation between the two models of warm hepatic ischemia. Our findings suggest that different therapeutic strategies are necessary to ameliorate the initial injury after low flow ischemia (hemorrhage) compared to cold (transplantation) or warm (Pringle maneuver) no-flow ischemia.
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PMID:Kupffer cell activation after no-flow ischemia versus hemorrhagic shock. 1210 17

Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression is an important mechanism underlying ischemia-reperfusion (I/R) induced neutrophil activation and tissue injury in other organs. However, I/R of the lungs has not been shown to upregulate ICAM-1 expression. We determined the time course profile of lung I/R-induced ICAM-1 expression and assessed the role of ICAM-1 in mediating neutrophil sequestration, transmigration, and I/R injury in the isolated blood-perfused rat lungs. I/R had a biphasic effect on ICAM-1 expression, an early downregulation and a late-phase upregulation. Superoxide dismutase and neutrophil depletion prevented the early ICAM-1 downregulation. The late-phase ICAM-1 upregulation coincided with the I/R-induced increase in pulmonary microvascular leakage index. ICAM-1 monoclonal antibody (MAb) reversed the I/R-induced increase in pulmonary microvascular leakage index, with control antibody being ineffective. Neither I/R nor ICAM-1 MAb affected lung MPO activity and circulating neutrophil count. Lung I/R significantly increased bronchoalveolar lavage fluid neutrophil count and the GSSG-to-(GSSG+GSH) ratio. ICAM-1 MAb blocked the I/R-induced increase in GSSG-to-(GSSG+GSH) ratio but had no effect on bronchoalveolar lavage fluid neutrophil count. Our results demonstrated that lung I/R up- and downregulates ICAM-1 expression depending on the duration of reperfusion. ICAM-1 upregulation is an important mechanism of I/R-induced pulmonary endothelial injury.
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PMID:Time course of lung ischemia-reperfusion-induced ICAM-1 expression and its role in ischemia-reperfusion lung injury. 1213 72

A timed profile of glutathione oxidation and reactive nitrogen species during reperfusion after cerebral ischemia in rat was obtained. Dialysate was collected every 25 min from a microdialysis probe inserted into the cerebral cortex before and after cerebral ischemia. NO2-, NO3-, and reduced and oxidized glutathione (GSH, GSSG) were detected by high-performance liquid chromatography. GSH and GSSG increased and reached a peak: 3408 +/- 1710% (mean +/- SE) at 25 min of reperfusion (P < 0.0001) and 329 +/- 104% at 50 min of reperfusion (P = 0.06), respectively. Oxidation ratio decreased from 0.82 +/- 0.04 to 0.42 +/- 0.07 (P < 0.0001) at 25 min of reperfusion. NO3- levels significantly decreased (68.3 +/- 9.1%) (P < 0.01) during ischemia and remained lower than the control value during reperfusion. NO2- levels did not significantly change. These data suggest that GSH releases during early phase of reperfusion and that its rapid oxidation contributes to prevent an increase in reactive nitrogen species.
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PMID:Relationship between oxidation of glutathione and reactive nitrogen species during the early-reperfusion phase of cerebral ischemia. 1219 54

Oxidative stress markedly alters protein function through redox modification of sulfhydryl groups present in cysteine residues. To explore the role of redox state in modulating cardiac K+ channels, this study examined the effects of sulfhydryl modifiers on the repolarizing transient outward current (Ito) in voltage-clamped myocytes from rat ventricle. Oxidized glutathione (GSSG; 5mM), an endogenous disulfide that specifically reacts with protein sulfhydryls, decreased maximum Ito amplitude from baseline by 49% when added to the external solution (P<0.05) and by 27% during internal dialysis (P<0.05). The membrane-impermeable disulfide, 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) did not alter Ito when added to the external solution, but it decreased current amplitude by 31% during internal dialysis (P<0.05). GSSG-mediated Ito inhibition varied in a frequency- and voltage-dependent manner, consistent with a state-dependent blocking mechanism. This phenomenon was also observed in myocytes internally dialyzed with DTNB or Cd2+, which also covalently binds to free sulfhydryls. Inhibition of Ito by GSSG was not reversed by washout alone, consistent with the stable nature of covalently-modified sulfhydryl groups. However, when myocytes pretreated with GSSG were dialyzed with the reducing agent dithiothreitol, Ito amplitude increased significantly by 42% (P<0.05). These data suggest that alpha-subunits underlying Ito, or associated proteins, have one or more sulfhydryl groups within the cytoplasmic domain that directly modulate channel activity in response to changes in cell redox state. Redox modulation of Ito channels may be an important post-translational mechanism contributing to acute changes in cardiac repolarization under conditions of oxidative stress, such as ischemia and reperfusion.
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PMID:Sulfhydryl modulation of K+ channels in rat ventricular myocytes. 1262 95

Ischemic preconditioning (IP) triggers protection of the liver from prolonged subsequent ischemia. However, the underlying protective mechanisms are largely unknown. We investigated whether and how IP protects the liver against reperfusion injury caused by Kupffer cell (KC)-derived oxidants. IP before 90 minutes of warm ischemia of rat livers in vivo significantly reduced serum alanine aminotransferase (AST) levels and leukocyte adherence to sinusoids and postsinusoidal venules during reperfusion. This protective effect was mimicked by postischemic intravenous infusion of glutathione (GSH), an antioxidative strategy against KC-derived H(2)O(2). Interestingly, no additional protection was achieved by infusion of GSH to preconditioned animals. These findings and several additional experiments strongly suggest IP mediated antioxidative effects: IP prevented oxidant cell injury in isolated perfused rat livers after selective KC activation by zymosan. Moreover, IP prevented cell injury and pertubations of the intracellular GSH/GSSG redox system caused by direct infusion of H(2)O(2) (0.5 mmol/L). IP-mediated resistance against H(2)O(2) could neither be blocked by the adenosine A2a antagonist DMPX nor mimicked by A2a agonist CGS21680. In contrast, H(2)O(2) resistance was abolished by the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, but induced when p38 MAPK was directly activated by anisomycin. In conclusion, we propose a novel concept of hepatoprotection by IP: protection of liver cells by enhancing their resistance against KC-derived H(2)O(2). Activation of p38 MAPK and preservation of the intracellular GSH/oxidized glutathione (GSSG) redox system, but not adenosine A2a receptor stimulation, seems to be pivotal for the development of H(2)O(2) resistance in preconditioned livers.
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PMID:Induction of cellular resistance against Kupffer cell-derived oxidant stress: a novel concept of hepatoprotection by ischemic preconditioning. 1254 Jul 78

Reduced tolerance of steatotic livers to ischemic injury is considered to correlate with impaired microcirculation. The aim of this study was to investigate the impact of heat-shock preconditioning (HSPC) on microcirculatory failure after ischemia/reperfusion (I/R) in steatotic livers by means of intra-vital fluorescence microscopy. Obese Zucker rats were used. In the HS group, rats underwent whole-body hyperthermia followed by 60-min partial liver ischemia. In group IR, rats were exposed only to ischemia. Microcirculation parameters (sinusoidal perfusion rate, sinusoidal diameter, leukocyte-endothelial interaction) were significantly better preserved in the HS group than in the IR group. Liver enzymes, oxygenated glutathione/reduced glutathione (GSSG/GSH) ratio, and electron microscopy showed less damage in the HS group. A marked expression of heat shock protein 72 (HSP72) and heme oxygenase (HO-1) was found only in the livers of group HS. HSPC mitigated the I/R injury of steatotic livers by preventing post-ischemic failure of microcirculation. This beneficial effect was found to be associated with the induction of HSP72 and HO-1.
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PMID:Heat-shock preconditioning protects fatty livers in genetically obese Zucker rats from microvascular perfusion failure after ischemia reperfusion. 1269 40

Increases in free radicals are believed to play a central role in the development of pulmonary ischemia/reperfusion (I-R) injury, leading to microvascular leakage and deterioration of pulmonary surfactant. Continued ventilation during ischemia offers significant protection against I-R injury, but the impact of alveolar oxygen supply both on lung injury and on radical generation is still unclear. We investigated the influence of hyperoxic (95% O2) and anoxic (0% O2) ventilation during ischemia on alveolar antioxidant status and surfactant properties in isolated rabbit lungs. Normoxic and hyperoxic ventilated, buffer-perfused lungs (n = 5 or 6) and native lungs (n = 6) served as controls. As compared with controls, biophysical and biochemical surfactant properties were not altered in anoxic as well as hyperoxic ventilated ischemic (2, 3, and 4 h) lungs. Assessment of several antioxidants (reduced glutathione (GSH), alpha-tocopherol (vitamin E), retinol (vitamin A), ascorbic acid (vitamin C), uric acid, and plasmalogens (1-O-alkenyl-2-acyl-phospholipids)) in bronchoalveolar lavage fluid (BALF) revealed a significant increase in antioxidant compounds under anoxic and hyperoxic ventilation, with maximum levels occuring after 3 h of ischemia. For example, GSH increased to 5.1 +/- 0.8 microM (mean +/- SE, p <.001) after 3 h of anoxic ventilated ischemia and to 2.7 +/- 0.2 microM (p <.01) after hyperoxic ventilated ischemia compared with native controls (1.3 +/- 0.2 microM), but did not significantly change under anoxic and hyperoxic ventilation alone. In parallel, under ischemic conditions, oxidized glutathione (GSSG) increased during hyperoxic (3 h: 0.81 +/- 0.04 microM, p <.001), but remained unchanged during anoxic (3 h: 0.31 +/- 0.04 microM) ventilation compared with native controls (0.22 +/- 0.02 microM), whereas F2-isoprostanes were elevated under both hyperoxic (3 h: 63 +/- 15 pM, p <.01) and anoxic (3 h: 50 +/- 9 pM, p <.01) ventilation compared with native controls (16 +/- 4 pM). We conclude that oxidative stress is increased in the lung alveolar lining layer during ischemia, during both anoxic and hyperoxic ventilation. This is paralleled by an increase rather than a decrease in alveolar antioxidant levels, suggested to reflect an adaptive response to oxidative stress during ischemia.
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PMID:Increase in alveolar antioxidant levels in hyperoxic and anoxic ventilated rabbit lungs during ischemia. 1473 92

Prospective epidemiological studies have shown that the incidence of numerous cardiovascular pathologies is correlated with body selenium status. However, it remains unclear whether selenium status also influences the outcome of myocardial infarction. The aim of the present study was to test whether dietary selenium intake affects myocardial necrosis induced by transient regional ischemia in vivo in rats. For this purpose, male Wistar rats received either a high-selenium (High-Se: 1.5 mg of Se/kg) or a low-selenium (Low-Se: 0.05 mg of Se/kg) diet for 10 weeks. Animals were subjected to 30 min of myocardial ischemia induced by coronary artery ligation followed by 60 min of reperfusion. Pre- and postischemic blood samples were collected for glutathione (GSH and GSSG) determination and for glutathione peroxidase (GSH-Px) assessment. Our results show that high-selenium intake reduces myocardial infarct size (High-Se: 25.16 +/- 1.19% versus Low-Se: 36.51 +/- 4.14%, p < 0.05), preserves postischemic GSH/GSSG ratio (High-Se: 1.37 +/- 0.37 versus Low-Se: 0.47 +/- 0.10, p < 0.05), increases plasma GSH-Px activity, and improves postischemic mean arterial pressure. In conclusion, preischemic body selenium status is a major determinant of the outcome of myocardial ischemia in vivo in rats probably because it influences the cellular redox status.
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PMID:Preischemic selenium status as a major determinant of myocardial infarct size in vivo in rats. 1524 60


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