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

Leukocyte adhesion may play a central role in the pathogenesis of preservation-reperfusion injury to liver grafts. We previously showed that lymphocyte adhesion to sinusoids is dependent on the length of cold ischemia. In the present study we examined the mechanisms of lymphocyte adherence after harvesting combined with a short and a long preservation time. The effects of lymphocyte adherence on liver function were also examined. Rat livers were stored at 1 degrees C in University of Wisconsin solution for 45 min or 30 hr and then reperfused at 37 degrees C in the isolated perfused rat liver with isogeneic lymphocytes in an asanguineous perfusate. The role of reactive oxygen intermediates was investigated with allopurinol, a vitamin E analog and ascorbate or superoxide dismutase and catalase. For us to determine the role of Kupffer cells, Kupffer cell blockade was produced by gadolinium chloride. Leukotriene B4 effects were examined with the lipooxygenase inhibitor, nordihydroguaiaretic acid. We evaluated the possible presence of mechanical obstruction by studying flow rates and the circulation of red blood cells. We examined the role of adhesion molecules by pretreating lymphocytes with trypsin or neuraminidase and by exposing livers to arabinogalactan. We investigated the effects of lymphocyte adhesion on liver function by comparing perfusate liver enzymes in livers reperfused with and without lymphocytes, with trypsinized lymphocytes and with an increased number of lymphocytes. Allopurinol significantly reduced hypoxanthine degradation, and nordihydroguaiaretic acid inhibited leukotriene B4 release into the perfusate. The ability of gadolinium chloride to inhibit Kupffer cells was shown by colloid carbon uptake. In livers harvested and preserved for 45 min, lymphocytes decreased about 40% during reperfusion. In livers preserved for 30 hr, the reduction was significantly greater (about 80%). Lymphocyte adherence was lessened in livers preserved for 45 min by all three of the reactive oxygen intermediate protectants and by gadolinium chloride. In contrast, neither reactive oxygen intermediate protectants nor gadolinium chloride reduced adherence in livers preserved for 30 hr. Nordihydroguaiaretic acid had no effect in livers preserved for either 45 min or 30 hr. Portal flow in livers preserved for 45 min and 30 hr was similar, suggesting an absence of mechanical obstruction, and this finding was supported by a complete absence of red cell trapping. Trypsinization of lymphocytes and exposure of livers to arabinogalactan significantly lessened lymphocyte adherence in livers preserved for 30 hr but not in those preserved for 45 min.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lymphocyte adherence in the reperfused rat liver: mechanisms and effects. 838 Jul 89

The salicylate trapping method was used to investigate the changes in hydroxyl radical (.OH) levels in the selectively vulnerable hippocampus compared to the cerebral cortex of gerbils subjected to a 10 min period of near complete forebrain ischemia. Salicylate-derived 2,5-dihydroxybenzoic acid (2,5-DHBA) was measured in sham-operated animals and at 1, 5, and 15 min of reperfusion. A basal level of 2,5-DHBA was also seen in non-ischemic gerbil brain, both in the hippocampus and cortex. The hippocampal basal level was 160% higher than in the cortex (P < .01). Treatment with the cytochrome P450 inhibitor SKF-525A (50 mg/kg s.c. 30 min before measurement) did not affect this basal level in either hippocampus or cortex, which argues against a contribution of metabolic salicylate hydroxylation as its source. In contrast, pretreatment with the arachidonic acid cyclo-oxygenase inhibitor ibuprofen (20 mg/kg s.c.) decreased (-68.8%) the level of salicylate hydroxylation in the hippocampus, but not the cortex. In animals subjected to 10 min of forebrain ischemia, a selective increase in 2,5-DHBA was observed in the hippocampus at 1 min of reperfusion which subsided by 5 min. No increase in salicylate hydroxylation was apparent in the cortex within the same time frame. The increase in .OH in the hippocampus at 1 min of reperfusion was accompanied by a significant decrease (-15.7%; P < .03) in the hippocampal levels of vitamin E. No loss of vitamin E was observed in the cortex at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydroxyl radical production and lipid peroxidation parallels selective post-ischemic vulnerability in gerbil brain. 838 Aug 74

The effect of incomplete 4 hr ischemia and subsequent 1 hr reperfusion of the rat brain on the density and affinity of alpha-adrenergic binding sites was investigated. To assess the involvement of oxygen-derived free radicals in the development of ischemic injury, we tested the effect of stobadine and vitamin E on putative changes of the binding parameters of alpha-adrenergic binding sites in ischemic and reperfused rat brains. Compared to the group of sham operated animals decreased density and increased affinity of [3H]dihydroergocryptine binding sites was found in cerebrocortical membranes of rats subjected to 4 hr incomplete ischemia and 1 hr reperfusion. The reduction of Bmax and Kd induced by ischemia and reperfusion of the brain was prevented by stobadine and vitamin E administration. Neither incomplete ischemia nor incomplete ischemia and subsequent reperfusion of the rat brain exerted significant effect on [3H]rauwolscine binding to alpha 2-adrenergic binding sites. Our results suggest that brain ischemia and reperfusion may affect the density and affinity of alpha 1- rather than of alpha 2-adrenergic binding sites. The beneficial effect of stobadine and vitamin E indicates that increased generation of oxygen free radicals might play a role in the development of these changes.
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PMID:Effect of incomplete ischemia and reperfusion of the rat brain on the density and affinity of alpha-adrenergic binding sites in the cerebral cortex. Prevention of changes by stobadine and vitamin E. 841 41

Lipid peroxidation, presumably the result of free radical-mediated injury, has been shown to occur during myocardial ischemia and reperfusion. Since vitamin E is a very effective, naturally occurring, chain-breaking antioxidant, it was investigated whether a vitamin E-supplemented diet increased myocardial tolerance towards ischemia and reperfusion in pigs. In addition to a standard diet which contained 30 mg vitamin E/kg (approximately daily vitamin E intake 30 mg), ten pigs were fed with 10 g vitamin E (all-rac-alpha-tocopherol acetate, Merck AG, Darmstadt, Germany) daily for at least 4 weeks. Ten control pigs remained on the standard diet. In an open chest preparation, the left anterior descending coronary artery was distally ligated for 45 min followed by 3 d of reperfusion. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was evaluated by sonomicrometry. Vitamin E concentrations in plasma and myocardium were measured by high-performance liquid chromatography. Global hemodynamic characteristics did not differ between the two groups. Oral pretreatment with vitamin E raised the plasma concentration of this vitamin from 1.1 +/- 0.3 to 5.0 +/- 1.0 mg/l and the myocardial content from 4.2 +/- 0.7 to 18.6 +/- 2.7 ng/mg fresh weight. Vitamin E treatment did not reduce infarct size, which amounted to 71.3 +/- 5% in the control group and to 71.7 +/- 8.2% in the treated animals. Furthermore, recovery of regional systolic shortening of the reperfused segment did not significantly differ in the two groups after 3 d of reperfusion; it measured 2 +/- 4% in the controls and 6 +/- 6% (p = 0.16) in the treated animals. Therefore, chronic, oral treatment with vitamin E which raised myocardial and plasma concentrations of this vitamin 4- to 5-fold did not increase myocardial tolerance towards ischemia and reperfusion in this animal model.
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PMID:Failure of chronic, high-dose, oral vitamin E treatment to protect the ischemic, reperfused porcine heart. 844 Nov 76

We assessed the protection afforded against myocardial ischemia/reperfusion by nitecapone in the Langendorff heart model using male Sprague-Dawley rats. We found that when present in the perfusate 10 microM nitecapone improved the mechanical function of the heart and lowered the enzyme leakage of lactate dehydrogenase after 40 minutes of global ischemia. In nitecapone treated hearts the content of oxidized proteins and lipids (carbonyl groups and endogenous lipid fluorescent products) decreased. Nitecapone partially prevented the loss of total sulfhydryl groups and vitamin E after ischemia and reperfusion. We suggest that the mechanism of nitecapone protection most likely involves direct antioxidant action and enhancing the activity of other antioxidants.
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PMID:Nitecapone protects the Langendorff perfused heart against ischemia-reperfusion injury. 848 62

A newly introduced compound, EPC-K1, represents a phosphate diester linkage of vitamin E and vitamin C. The effect of EPC-K1 on the reperfusion injury was evaluated in a heterotopic cardiac transplantation model using syngenic combination rats. Prior to the warm ischemia, 12mg EPC-K1/kg was administered intravenously to donor rats. After 15 min of warm ischemic time, hearts were harvested and perfused with 4 degrees C saline. After completion of the transplantation, recipient rats were also treated with intravenous 12 mg EPC-K1/kg, before reperfusion. Saline was used instead of EPC-K1 for both donors and recipients in the control group. On the 7th post-transplantation day, graft survival was 7 out of 8 in EPC-K1 group, versus 1 out of 9 in the control group (p < 0.001). Thiobarbituric acid-reactive substance levels in the recipient serum, three hours after reperfusion, were significantly limited, in the group in which EPC-K1 was administered only to donors. But it was not possible to clarify whether the effect of EPC-K1 is primarily at the donor or recipient levels at this time. These results indicate that EPC-K1 may reduce reperfusion injury after cardiac transplantation. This beneficial effect may be mediated by the hydroxyl radical scavenging properties of EPC-K1.
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PMID:Beneficial effect of EPC-K1 on the survival of warm ischemic damaged graft in rat cardiac transplantation. 850 49

Aimed at improving animal fertility and health, diets for farm and laboratory animals have over the last few years been supplemented with increasing amounts of the antioxidant vitamin E. We now demonstrate by intravital microscopy that feeding hamsters with a vitamin E-supplemented "standard" rodent diet (60 ppm vitamin E) significantly reduces the microvascular manifestations of ischemia/reperfusion injury when compared to animals fed a nonsupplemented diet. Postischemic leukocyte adhesion to venular endothelium was reduced from 770 +/- 204 cells/mm2 at 24 h after reperfusion in control animals on the nonsupplemented diet to 403 +/- 105 cells/mm2 in animals on the "standard" rodent diet (means +/- SD, n = 7 animals per group, p < 0.01). Animals on the nonsupplemented diet showed a dramatic loss of capillary perfusion density until 7 days after reperfusion (to 21 +/- 13% of preischemic baseline values), whereas this loss was significantly attenuated (to 71 +/- 12% of preischemic values, p < 0.01) in animals on the "standard" rodent diet. No difference in the extent of reperfusion injury was seen between animals on the "standard" rodent diet and animals on diets with substantially higher vitamin E supplements (300 ppm-30,000 ppm). Besides underscoring the benefit of vitamin E in reducing the extent of ischemia/reperfusion injury, this study raises the concern that vitamin E supplements in "standard" laboratory animal diets may have a far-reaching impact on biomedical research by jeopardizing established animal models of disease.
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PMID:Impact of vitamin E supplement in standard laboratory animal diet on microvascular manifestation of ischemia/reperfusion injury. 858 69

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

The possibility that verapamil (CAS 52-53-9) may intensify the efficacy of vitamin E in preventing the ischemia-reperfusion-caused biochemical dearrangement in rat cerebral cortex was investigated. A daily injection of vitamin E at i.m. dose of 175 mg/kg b.wt. for 7 days prior to subjecting the rats to 1 h bilateral occlusion of the common carotid arteries followed by reperfusion for another 1 h, moderately diminished the ischemia-reperfusion-induced increase in the activity of lactate dehydrogenase and in formation of conjugated dienes as well as in the conversion of xanthine dehydrogenase-->xanthine oxidase in cerebral cortex of rats. However, concomitant injection of verapamil at i.m. dose of 0.68 mg/kg b.wt. 15 min prior to ischemia-reperfusion together with vitamin E pretreatment afforded an elegant combined therapy that effectively abolished the dearrangement caused by ischemia-reperfusion in the above parameters. These results indicated that the protective efficacy of vitamin E against ischemia/reperfusion-induced biochemical dearrangement in cerebral cortex was intensified by concomitant use of verapamil.
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PMID:Influence of verapamil on the efficacy of vitamin E in preventing the ischemia-reperfusion-induced biochemical dearrangement in cerebral cortex of rat. 884 34

A novel group of compounds, the 21-aminosteroids ("lazaroids"), have been designed that are potent inhibitors of oxygen free radical-induced, iron-catalyzed lipid peroxidation (LP) in microvascular and nervous tissue. One of these, tirilazad mesylate (U-74006F), has been selected for clinical evaluation as a cerebroprotective agent. In vitro studies suggest that tirilazad exerts its antioxidant activity by multiple mechanisms including: increasing membrane stability, scavenging of lipid peroxyl radicals, reducing LP-induced arachidonic acid release, decreased formation or scavenging of hydroxyl radicals, and maintenance of the levels of endogenous vitamin E. The major site of action appears to be the blood-brain barrier based upon its known localization in cerebrovascular endothelium and numerous studies showing an attenuation of subarachnoid hemorrhage (SAH), injury, and ischemia-induced blood-brain barrier permeability. Tirilazad has demonstrated neuroprotective efficacy in multiple preclinical models of spinal cord and head injury, SAH, and focal cerebral ischemia, as measured by a decrease in cerebral vasospasm, blood-brain barrier compromise, post-traumatic ischemia, edema, ischemic neuronal necrosis and infarction, and improved neurological recovery. This efficacy is correlated with a reduction in markers of oxygen radical-induced LP. Phase III clinical trials are currently ongoing in spinal cord and head injury, SAH, and ischemic stroke. Initial results from a European/Australian/New Zealand trial in SAH have shown a significant decrease in mortality and an increase in the incidence of good recovery.
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PMID:Inhibition of lipid peroxidation in central nervous system trauma and ischemia. 884 48


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