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

The effect of 32 mM ascorbate on the time courses of phosphocreatine (PCr), inorganic phosphate (Pi), adenosine triphosphate (ATP) and intracellular pH in rat skeletal muscle during ischemia and reperfusion was investigated in vivo using 31P nuclear magnetic resonance (NMR) spectroscopy. Ascorbate was administered intravenously prior to induction of ischemia and at the time of reperfusion. The changes in PCr/(PCr+Pi), ATP and pH were similar in the non-treated and in the treated groups during ischemia. PCr/(PCr+Pi) fell to < 10% and ATP to approximately 30% of the preischemic values after 4 hours of arrested circulation, and pH decreased considerably. Postischemic reperfusion was followed continuously for 150 minutes. At the time of reflow, treatment with ascorbate had an immediate, positive effect on the recovery of high energy phosphates and pH. The level of PCr/(PCr+Pi) was 86% higher (p < 0.001) and the ATP level was 40% higher (p < 0.001) in the treated group than in the control group by the end of the reperfusion period. The results provide in vivo evidence for a salvaging effect of ascorbate on ischemia-reperfusion injury in skeletal muscle, probably owing to its antioxidant function and other ancillary effects, mainly its provision of additional buffer capacity.
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PMID:In vivo 31P nuclear magnetic resonance evidence of the salvage effect of ascorbate on the postischemic reperfused rat skeletal muscle. 783 May

Older gerbils are more sensitive to ischemia/reperfusion injury (IRI) than younger ones. Utilizing 31P-NMR to monitor in vivo pH and high energy phosphates of brain cortex undergoing an IRI showed that cortical intracellular pH decreased to 6.35 after ischemia and then increased with reperfusion, but older gerbils required significantly more time to recover than younger animals. Brain high energy phosphates dropped during ischemia but rebounded within 20 min reperfusion in younger gerbil brain but remained significantly lower in older gerbil brain for 50 min. These data suggest that IRI-induced brain acidification may enhance oxidative damage. In an in vitro system it was shown in both young and old brain homogenate that peroxidation rate increased when the pH of the incubation medium was decreased from 7.4 to 6.4. This was true in the presence or absence of an ADP/Fe/Ascorbate system in both young and old brain homogenate. Enhancement of peroxidation rate by ADP/Fe/Ascorbate addition was much more pronounced at pH 7.4 (30- to 40-fold increase) as compared to pH 6.4 (7.8- to 9.5-fold increase). This data can be interpreted to indicate that the lower pH makes endogenous Fe more available to catalyze oxidative damage. The fact that brain pH and high energy phosphates remain lower in older gerbil brains during IRI suggests that brain mitochondria from older animals are less capable of responding to a large oxidative stress brought on by an IRI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age effect on brain pH during ischemia/reperfusion and pH influence on peroxidation. 783 86

Free radicals have been implicated in the cause of ischemia-reperfusion injury. Various agents have been used in an attempt to reduce ischemia-reperfusion injury pharmacologically, including free radical scavengers. Vitamin C (ascorbic acid), a well-known free radical scavenger, has not, to the best of our knowledge, been evaluated in this respect. Previous work at our institution has shown that vitamin C decreases capillary permeability, thus significantly reducing fluid resuscitation requirements in postburn cases. Because this is due in part to the scavenging effect of vitamin C on free radicals, we investigated the role, if any, of vitamin C on ischemia-reperfusion injury in a rat epigastric island skin flap model. Twenty-four adult Sprague-Dawley rats were divided into control and vitamin C groups. Superficial epigastric island skin flaps measuring 6.0 x 3.5 cm were raised. Pedicles were isolated and occluded with microvascular clamps for 6 hours. The flaps were then sutured back to their beds over Steri-Drape barriers. Fifteen minutes before reperfusion, the control group flaps were perfused via femoral artery cannulation with normal saline (2.5 ml/kg). The vitamin C-treated group was perfused in a similar fashion with 2.5 ml/kg of a vitamin C/normal saline solution (27 mg/ml). The animals were observed for 7 days, and the percentage of flap survival was determined using a paper template technique. The vitamin C-treated group demonstrated a significantly higher percentage of flap survival than did the control group (25.8% mean vs. 7.5% mean, p < 0.025). In this animal model, vitamin C reduced or limited reperfusion injury after 6 hours of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vitamin C reduces ischemia-reperfusion injury in a rat epigastric island skin flap model. 788 53

The rat gastric mucosa, superfused with 0.1 N HCl, was investigated following 15 min of hemorrhagic shock and 30 min of retransfusion after pretreatment with ascorbate (1 mg/100 g b.w. or 5 mg/100 g b.w.). The size of the ischemic areas and the amount of mucosal bleeding using 51Cr labeling of red blood cells were assessed. Ischemic areas developed during shock. Following retransfusion, bleedings occurred at the border zones between ischemic and surrounding circulated areas. Ascorbate in both doses protected the gastric mucosa by reducing the amount of bleeding following 30 min of retransfusion as well as by reducing the area of ischemia 5 min after retransfusion.
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PMID:Ascorbate reduces gastric bleeding after hemorrhagic shock and retransfusion in rats. 800 79

Ca(2+)-release channel or ryanodine receptor is known to be involved in physiologic Ca(2+)-release from sarcoplasmic reticulum in skeletal and cardiac muscle. A variety of chemical oxidants and in particular SH-oxidizing reagents have been shown to activate Ca2+ release. However, the role of the oxidative modification of the channel in the physiologic mechanism(s) of Ca2+ release and in pathologic states of the muscle remains to be elucidated. Ascorbate/iron redox couple is known to be an efficient generator of oxygen radicals and semidehydroascorbyl radicals. Ascorbate/iron was shown to be released from cardiomyocytes during ischemia-reperfusion and was suggested to be involved in the ischemia-reperfusion injury and cardiomyocyte death. To understand the potential contribution of ascorbate/iron to Ca2+ release mechanism(s), calcium release channels from skeletal sarcoplasmic reticulum (SR) were reconstituted in artificial planar bilayers to examine the effects of this redox couple on the channel activity. Ascorbate elicited a transient (about 2 min) but dramatic increase of open-time probability of the channel. At pCa = 7.0, the presence of EGTA blocked ascorbate induced activation of release channels. However, when exogenous iron was added, ascorbate activated Ca2+ release channels, even in the presence of EGTA. ESR measurements demonstrated that semidehydroascorbyl radicals were generated from ascorbate in the absence of EGTA. The semidehydroascorbyl radical ESR signal was quenched by EGTA in the absence (but not in the presence) of exogenous iron. Thus, the production of ascorbyl radicals was associated with increased channel activity. In the presence of heparin, ascorbate plus iron elicited a long-lasting activation of the channel which had conductance gCa2+ = 100 pS characteristic for the ryanodine receptor and which could be blocked by the ryanodine channel inhibitor, ruthenium red. In conclusion the physiologically relevant redox couple--ascorbate/iron--at physiologic concentrations can activate Ca2+ channels in sarcoplasmic reticulum vesicles.
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PMID:Ascorbate/iron activates Ca(2+)-release channels of skeletal sarcoplasmic reticulum vesicles reconstituted in lipid bilayers. 831 55

Complete, reversible forebrain ischemia was induced with a seven-vessel occlusion rat model. Previous studies of ischemic (M. A. Sciamanna, J. Zinkel, A. Y. Fabi, and C. P. Lee, 1992, Biochim. Biophys. Acta 1134, 223-232) rat brain mitochondria (RBM) showed that ischemia of 30 min caused an approximately 60% decrease in State 3 respiratory rates with both succinate and NAD-linked substrates and also in energy-linked Ca2+ transport. No significant change was seen in the State 4 rates. The inhibition of respiration could be prevented by EGTA or ruthenium red. In this paper it is shown that reperfusion (5 h) following ischemia (30 min) further impaired RBM respiratory activities (succinate and NAD-linked substrates). The presence of EGTA or ruthenium red in the assay medium did not protect against ischemia/reperfusion-induced injury. The effects of ascorbate, an oxygen radical scavenger, were studied. RBM isolated from ascorbate-treated animals (0.8 mg ascorbate/kg body weight) after ischemia (30 min) alone showed only a slight increase in State 3 (approximately 25%) and a decrease in State 4 (approximately 20%) activities with succinate, when compared to untreated 30-min ischemic animals, whereas, with glutamate+malate little or no effect was seen. The respiratory activities of RBM from ascorbate-treated, ischemic/reperfused (30 min/5 h) rats were restored to approximately 65% of controls levels. Ascorbate protection was dose-dependent with maximum protection at 0.8 mg ascorbate/kg body weight of rat. The k of succinate oxidase-supported Ca2+ uptake also returned to 62% of control values. Protection by ascorbate was most effective when administered prior to the onset of ischemia and provided partial protection when administered after the onset of reperfusion. These results suggest that ischemia-induced injury is primarily mediated by disruption of cellular Ca2+ homeostasis, and reperfusion-induced injury by peroxidative events.
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PMID:Ischemia/reperfusion-induced injury of forebrain mitochondria and protection by ascorbate. 837 58

Platelet activating factor (PAF) antagonists have been recently documented to possess beneficial effects on ischemia and ischemia-reperfusion-induced myocardial injury. Moreover, their ameliorative effect has been ascribed to their capacity to scavenge or impair oxygen free radical generation. In the present study, the effect of PAF antagonists BN 52021, BN 52030 and BN 52039 on iron-initiated lipid peroxidation (LPO) was investigated in murine ventricular membranes and compared with a potent antioxidant, U-74500A ( a lazaroid). Fe2+ -Vitamin C induced a concentration and time-dependent LPO, measured as thiobarbituric acid reactive substances (TBARS) by standard malondialdehyde (MDA) curve. PAF antagonists were pretreated to ventricular membranes in 5 microM and higher concentrations. All three agents inhibited Fe2+ -Vitamin C-initiated LPO in a concentration-dependent manner with an IC50 value ranging from 103.7 to 373.5 microM; however, they were less potent than U-74500A (IC50 6.8 microM). Inhibition of LPO may not be due to their classical pharmacological actions, but may be attributed to characteristic chemical structure or their physicochemical interactions with biological membranes. Inhibition of LPO may provide additional cardioprotective activity and thus reaffirms their use in ischemic heart disease.
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PMID:Antiperoxidative effects of platelet activating factor antagonists against iron-dependent lipid peroxidation in murine ventricular membranes. 864 99

The effect of acute endotoxin-induced septic shock on myocardium oxidative stress after low or high vitamin C and/or E dietary supplementation was studied in guinea pigs, laboratory animals which, like human, do not have capacity for ascorbate synthesis. Neither the antioxidant enzymes or GSH were modified by endotoxin and vitamin treatments. Vitamin E showed a strong capacity to protect the myocardium against both enzymatic and non-enzymatic lipid peroxidation even in the presence of endotoxin. Vitamin C supplementation increased heart ascorbate whereas endotoxic shock totally depleted the heart ascorbate of vitamin C supplemented animals without changing vitamin E. Endotoxin significantly increased myocardium uric acid, a marker of ischemia induced oxidative stress, in animals fed with low vitamin C levels. This increase was totally prevented in vitamin C supplemented, but not in vitamin E supplemented animals. Strongly depressed levels of plasma vitamin C have been recently described in sepsis in human patients. The results suggest that ascorbate is a primary antioxidant target in the heart of endotoxin treated mammals lacking the capacity to synthesize ascorbate and that ascorbate can have a protective value against endotoxin-induced free radical damage in the myocardium. Implications of these results for the possible preventive role of vitamin C in humans during sepsis are discussed.
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PMID:Endotoxin depletes ascorbate in the guinea pig heart. Protective effects of vitamins C and E against oxidative stress. 876 Oct 15

Tissue damage in ischemia/reperfusion injury may be mediated by oxidative stress caused by reactive oxidant species. Since such reactive species are difficult to measure directly, changes in antioxidant concentrations are often used as an indication of oxidative stress. In this study, microdialysis membranes were inserted into the livers of anesthetized rats to determine the effects of ischemia/reperfusion on the extra-cellular concentrations of two antioxidants, uric acid and ascorbic acid. Total hepatic ischemia was induced for 30 min by clamping the portal triad and was followed by 60 min of reperfusion. Uric acid and ascorbic acid concentrations were measured in microdialysis perfusates by high-performance liquid chromatography with electrochemical detection. Initial uric acid and ascorbic acid concentrations were high after insertion of membranes into the liver and decreased rapidly within 90 min (P < 0.001; ANOVA with repeated measures). Uric acid concentrations increased over 300% after ischemia and by 600% during the first 30 min of reperfusion (n = 8; P < 0.05). Ascorbic acid concentrations were 60% higher than controls after ischemia and 90% higher during the first 30 min of reperfusion (n = 8; P < 0.05). Alterations in concentrations of these redox-active molecules may be associated with oxidative stress in liver extracellular fluid during ischemia/reperfusion.
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PMID:Ischemia/reperfusion alters uric acid and ascorbic acid levels in liver. 880 65

Oxidative stress, assessed by tissue ascorbate loss following ischemia, is greater in male than female rat brain. The factors mediating this gender difference are unclear. The goal of the present studies was to determine the influence of gonadal sex hormones on this difference. Three weeks prior to experiment, adult Long-Evans male and female rats were gonadectomized for comparison with controls. Ascorbate and glutathione levels were determined in brain and plasma under basal conditions and in brain after one-hour decapitation ischemia, using liquid chromatography with electrochemical detection. Basal ascorbate levels in brain were 6-9% higher in males than in females, whereas plasma levels were 100% higher in males. After gonadectomy, the gender difference in plasma ascorbate levels was lost, while the effect on basal brain levels depended upon region. Ischemia-induced losses in brain ascorbate were three-fold greater in control males compared to control females. Significant losses occurred in frontal cortex, hippocampus, and cerebellum in males during ischemia, whereas loss in females was significant in cerebellum only. After gonadectomy, increased ascorbate loss was seen in all female brain regions, indicating enhanced oxidative stress. This increase eliminated the gender difference in loss; male ascorbate loss was comparatively unaffected by gonadectomy. Glutathione levels and loss were unaffected by either gender or gonadectomy, indicating differences in regulation from that of ascorbate. These findings provide evidence for the hypothesis that protection against oxidative stress is afforded by ovarian sex hormones, thus decreasing the potential for oxidative cell damage in females compared to males.
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PMID:Enhanced oxidative stress in female rat brain after gonadectomy. 894 21


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