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

Calcium antagonists reduce ischemic injury, and anti-free-radical interventions may reduce reperfusion injury. However, the effects of treatment with both interventions have never been investigated. In the present study, anesthetized rabbits underwent 30 minutes of coronary artery ligation, which was followed by 5.5 hours of reflow. Eight animals in each group received: (1) the calcium antagonist gallopamil during ischemia, (2) the oxygen radical scavenger superoxide dismutase during reperfusion, (3) combined treatment with gallopamil and superoxide dismutase, and (4) saline solution. All groups were similar with respect to collateral flow during ischemia and extent of risk region. Infarct size averaged 60.2% +/- 5.5% of risk region in controls and was significantly smaller (p < 0.001) in rabbits that were treated with either gallopamil (28.1% +/- 3.4%) of superoxide dismutase (29.3% +/- 3.2%). Little further reduction in infarct size was observed with combination therapy (22.9% +/- 3.2% of risk region; p = NS). Superoxide dismutase had no effects on hemodynamics, whereas gallopamil significantly reduced heart rate, mean arterial pressure, and rate-pressure product. However, the reduction in infarct size that was observed in gallopamil-treated rabbits significantly exceeded the expected value in this group after corrections were made for changes in these determinants of ischemic injury. Therefore we investigated whether other factors may have contributed to the beneficial effects of gallopamil. In vitro the drug had no oxygen radical scavenging activity, nor did it exert antioxidant effects. In addition, gallopamil did not affect neutrophil function. In conclusion, in this acute model myocardial cell necrosis was significantly reduced either by administration of a calcium antagonist during ischemia or by removing oxygen radicals during reperfusion. However, superoxide dismutase administration did not further reduce infarct size when given to animals that had been treated with gallopamil. Since gallopamil has no direct effect on several mechanisms of reperfusion injury, these data suggest that calcium antagonists, by decreasing myocardial oxygen demand during ischemia, may indirectly reduce oxygen radical damage during subsequent reperfusion.
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PMID:The effects of calcium channel antagonist treatment and oxygen radical scavenging on infarct size and the no-reflow phenomenon in reperfused hearts. 841 6

The aim of the present study was to examine the effect of exposing animals to 100% oxygen instead of room air on renal function and endogenous antioxidant enzymes of the postischemic reperfused rat kidney. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) were determined in the homogenate of the left kidney after 45 min of ischemia, caused by clamping the left renal artery, 10 and 90 min after reperfusion while the animals breathed room air or 100% O2. The right kidney served as a control. The possible influence of trapped blood in the clamped kidney was also investigated by the use of a correction factor based on the Hb concentration in the homogenate. The results indicate that such correction is necessary as the blood adds significant antioxidant activity. The activities of all 3 enzymes after 45 min of ischemia decreased significantly in the left (ischemic) compared to the right (control) kidney, to 64% of the control levels for catalase, 58% for SOD and 49% for GPX. After 10 min of reflow, a further decrease in the activities of catalase (to 49%) and of GPX (to 29%) was found. SOD activity, however, increased to 64%. After 90 min of reperfusion, restoration toward normal levels was noticed (SOD activity increased to 70%, catalase to 76% and GPX to 58%). Breathing 100% O2 resulted in a significant decrease in all enzyme activities (to 38.6% for catalase, 45% for SOD and to 27.4% for GPX). This inactivation can be explained by increased reactive oxygen species (ROS) activity during hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of oxygen tension on activity of antioxidant enzymes and on renal function of the postischemic reperfused rat kidney. 845 Sep 13

Superoxide anion radical (O2-) is one factor related to ischemia/reperfusion injury to the liver. The sites of O2- production and injury have yet to be determined. Superoxide dismutase (SOD), a specific scavenger for O2-, has an inhibitory effect on injury caused by O2-. SOD is of low molecular weight; hence, it has a short half-life in the circulating blood. Mannosylated SOD is taken up in sinusoidal endothelial cells of the liver by receptor-mediated endocytosis. In rats with an occluded inflow against 70% of the liver for 30 min followed by reperfusion there were elevations of serum aspartate aminotransferase and alanine aminotransferase, and lipid peroxide concentrations in liver tissue were significantly inhibited by intravenous administration of mannosylated SOD compared to treatment with normal saline. Electron microscopic examination showed that mannosylated SOD protected against damage to the sinusoidal endothelial cells caused by ischemia/reperfusion and that conventional SOD had no such protective effect. Thus, O2- produced by ischemia/reperfusion apparently damages sinusoidal endothelial cells, and damage to hepatic parenchymal cells is secondary. Mannosylated SOD deserves further study for possible use in surgical resection of the liver and for liver transplantations.
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PMID:Mannosylated superoxide dismutase inhibits hepatic reperfusion injury in rats. 859 29

Prolonged cold ischemia time and the generation of free oxygen radicals during reperfusion are risk factors for allograft arteriosclerosis. Growth factors are the main pro-proliferative mediators of smooth muscle cells in classical and in allograft arteriosclerosis. Superoxide dismutase is an enzyme that catalyzes the dismutation of superoxide anions into hydrogen peroxide. This study was designed to investigate which smooth muscle cell growth factor contribute to the formation of arteriosclerosis in syngenic vascular grafts with prolonged ischemia time, and whether perioperative intravenous administration of recombinant human superoxide dismutase (rh-SOD) prevents arteriosclerosis in these grafts. DA aortas were transplanted into DA recipients. One group of transplants was made with a short ex vivo ischemia time (15 min), while the other group transplant grafts was stored for 24 hr in cold saline. In addition to morphometric quantitation of the histological alterations, RNA isolated from grafts with short cold ischemia time in a semiquantitative polymerase chain reaction specific for various known smooth muscle cell growth factors. Syngeneic grafts with prolonged cold ischemia time showed severe intimal thickening and prominent medical necrosis, which were not seen in control groups. Approximately 3-fold levels of insulin-like growth factor-1 were found in ischemic syngeneic grafts compared with non-ischemic syngenic grafts, whereas epidermal growth factor levels were slightly lower. No changes in other growth factor mRNAs were found. Perioperative treatment with rh-SOD did not have significant effect on the extent of intimal thickening nor on the intensity of medial necrosis in grafts with prolonged ischemia time, and administration of rh-SOD did not change the expression level of insulin-like growth factor-1 in the grafts, either.
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PMID:Lack of effect of recombinant human superoxide dismutase on cold ischemia-induced arteriosclerosis in syngeneic rat aortic transplants. 862 79

This study determined the role that oxygen-derived free radicals played in the production of gastric injury in rats challenged orally with concentrated ethanol or subjected to vascular compromise. In the ethanol study, rats were pretreated with a variety of free radical scavengers or enzyme inhibitors prior to exposing the stomach to 100% ethanol. At sacrifice, the degree of macroscopic damage to the glandular gastric mucosa was quantified. In separate studies, the effects of ethanol on gastric mucosal levels of enaldehydes (malondialdehyde and 4-hydroxynonenal) were examined as an index of lipid peroxidation. Superoxide dismutase and catalase pretreatment were without benefit in reducing injury in our ethanol model, excluding potential contributory roles for the superoxide anion or hydrogen peroxide, respectively. Dimethyl sulfoxide and desferoxamine were likewise without protective capabilities, eliminating a role for the hydroxyl radical. Allopurinol, a xanthine oxidase inhibitor, provided no protection under acute conditions, even though partial protection was noted when administered chronically. Further, enaldehyde levels were not increased over control levels in alcohol-exposed mucosa, indicating no enhanced lipid peroxide formation. In contrast, in animals in which ischemia to the stomach was induced followed by reperfusion, marked gastric injury was observed in combination with enhanced enaldehyde levels. Prevention of enaldehyde formation by a 21-aminosteroid concomitantly prevented injury induced by ischemia-reperfusion. These findings support the conclusion that ischemia-reperfusion injury to the stomach is an oxygen-derived free radical process whereas ethanol-induced injury clearly involved some other process. Although allopurinal was partially protective against ethanol damage when administered chronically, observations in other models of injury suggest that this action is independent of its inhibitory effect on xanthine oxidase.
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PMID:Gastric injury induced by ethanol and ischemia-reperfusion in the rat. Differing roles for lipid peroxidation and oxygen radicals. 865 47

To gain insight into the mechanisms responsible for muscle dysfunction after ischemia-reperfusion, a rat spinotrapezius muscle preparation was developed which enabled sequential measurements of in vivo maximum tetanic force production and cell death assessed using digital microfluorographic determination of propidium iodide (PI) staining. After 60 min of no-flow ischemia, maximum tetanic force fell significantly during 90 min of reperfusion compared with control, nonischemic muscles. The most striking fall was evident within 30 min of reperfusion and occurred concomitant with an explosive increase in PI-positive myocyte nuclei. Treatment with the oxygen radical scavenger, dimethylthiourea, attenuated both the fall in force and increased PI staining. Indeed, the rise in PI-positive nuclei correlated closely (r= 0.728) with the reduction of maximum tetanic force developed following ischemia and reperfusion under all conditions. Superoxide dismutase also attenuated the rise in PI-positive nuclei. Assessment of mitochondrial inner membrane potential (deltapsi) using Rhodamine 123 fluorescence revealed that myocytes with the lowest initial mitochondrial membrane potential were subject to the greatest injury after 90 min of reperfusion (r= 0.828). These results support the hypothesis that myocyte injury, as visualized by PI-staining, reflects an impaired contractile function in fibers with a low oxidative potential which is likely mediated by oxygen radicals.
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PMID:Temporal correlation between maximum tetanic force and cell death in postischemic rat skeletal muscle. 867 60

Superoxide dismutase (SOD) scavenges free superoxide radicals generated during reperfusion of ischemic tissue and decreases cellular injury. A synthetic manganese-based metalloprotein superoxide dismutase mimic, SC52608 (Monsanto Co.), was tested in the isolated rabbit rectus femoris muscle flap to determine its effects on ischemia-reperfusion injury. The results of our experiments analyzing 38 isolated rectus femoris muscles in 19 New Zealand White rabbits show that administration of SC52608 at the onset of 4 hours of warm ischemia and before reperfusion significantly increases the survival of the muscle from 20.0 +/- 4.9 percent (control, HEPES) to 81.5 +/- 4.6 percent (SC52608) (p < 0.001). It preserved functional contraction in 8 of 10 muscles; only 1 of 12 control muscles (control, HEPES) had contractions (p = 0.0015). SC52608 decreased the neutrophil density from 4.63 +/- 0.6 x 10(4) cells/mm2 in the control (HEPES) muscle to 2.71 +/- 0.6 x 10(4) cell/mm2 in muscles perfused with SC52608 (p = 0.03). The level of malonyldialdehyde decreased from 6.12 +/- 0.26 nmol/gm (control, HEPES) to 4.64 +/- 0.41 nmol/gm (SC52608) (p = 0.0028). Postoperative weights of the muscles showed no statistical difference (p = 0.14) between the controls (16.0 +/- 0.9 gm) and the SC52608 (18.1 +/- 0.7 gm). Our investigation shows that direct intraarterial infusion of a synthetic superoxide dismutase mimic at the onset of ischemia and prior to reperfusion can reduce reperfusion injury in skeletal muscle.
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PMID:Prevention of ischemia-reperfusion injury with a synthetic metalloprotein superoxide dismutase mimic, SC52608. 877 95

To assess the role of reactive oxygen species and nitric oxide (NO) in the genesis of reperfusion-induced arrhythmias, the effects of reactive oxygen species scavengers and NO synthase inhibitors on the incidence of ventricular fibrillation and irreversible ventricular fibrillation (mortality) were examined. Hearts of anesthetized rats were subjected to 4 min regional ischemia followed by 4 min reperfusion. The animals were treated i.v. with superoxide dismutase, a O2- scavenger, catalase, a H2O2 scavenger, dimethylthiourea, a .OH scavenger, or NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-L-arginine (L-NNA), NO synthase inhibitors. Superoxide dismutase (430 and 4300 U/kg/min) reduced the mortality from 93% to 43% and 57%, respectively, whereas treatment with catalase or dimethylthiourea did not affect these arrhythmias. L-NAME (0.1 and 0.3 mg/kg/min) reduced the mortality from 93% to 50% and 43%, respectively. L-NNA (0.3 mg/kg/min) reduced the mortality from 93% to 50%. This reduction by the NO synthase inhibitors was abolished by administration of L-Arg. However, L-Arg blocked neither a small increase in systolic blood pressure nor a decrease in heart rate elicited by the NO synthase inhibitors. The combinated treatment of superoxide dismutase (4300 U/kg/min) with L-NAME (0.3 mg/kg/min) reduced the mortality from 93% to 7%. These results suggest that the genesis of reperfusion-induced arrhythmias observed in this model may be in part due to O2- and NO.
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PMID:Involvement of superoxide and nitric oxide in the genesis of reperfusion arrhythmias in rats. 881 24

This study investigated the possible contribution of microvascular vasoconstriction to no-reflow following ischemia/reperfusion in a mouse skeletal muscle model. Using paired cremaster muscles, arterioles of diameter 10-100 microns were directly viewed and measured by the use of an in vivo videomicroscopy before and after a 6-hr period of complete ischemia at 27 degrees C. Following ischemia/reperfusion, feeder and arcading arterioles constricted significantly to 54.5 and 62% of pre-ischemic baseline diameters respectively (P < .05). While the calcium antagonist diltiazem and nitroprusside were both able to reverse arteriolar constriction, endothelium-dependent acetylcholine-induced dilatation was markedly impaired following reperfusion (P < 0.05). Superoxide dismutase did not attenuate the microvascular response, suggesting that the mechanism is likely to be at least partly free radical-independent.
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PMID:Characterization of microvascular vasoconstriction following ischemia/reperfusion in skeletal muscle using videomicroscopy. 889 74

Brain ischemia reperfusion causes increased formation of reactive oxygen species (ROS). Activity of the mitochondrial enzyme pyruvate dehydrogenase (PDH) has been shown to undergo a significant decrease following reperfusion of the ischemic tissue. We have examined the effect of a superoxide radical-generating system (xanthine oxidase/hypoxanthine, XO/HX) on the activity of this enzyme. Incubation of PDH in the presence of XO/HX resulted in its inactivation. The degree of the inactivation was dependent on the amount of XO present, which correlated linearly with the concentration of superoxide radical generated by this system. The activity of lactate dehydrogenase, an enzyme resistant to inactivation by ischemia reperfusion, was not affected by this system. Superoxide dismutase partially prevented and catalase exerted a nearly complete protective effect against the inactivation of PDH. Deferoxamine was partially protective. The sulfhydryl protective reagents, dithiothreitol and glutathione, prevented the inactivation of PDH, even though to varying degrees, which implicates sulfhydryl oxidation. A hydroxyl radical-generating system (hydrogen peroxide irradiated with ultraviolet radiation) effectively inactivated PDH. These results demonstrate that PDH is susceptible to damage and inactivation by ROS and point to the involvement of Fenton chemistry and hydroxyl radicals formed through it in PDH inactivation by XO/HX. A similar mechanism may be responsible for the PDH inactivation during ischemia/reperfusion.
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PMID:Reactive oxygen species-mediated inactivation of pyruvate dehydrogenase. 895 77


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