Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of human extracellular-superoxide dismutase type C (EC-SOD C) to limit infarct size after ischemia and reperfusion was explored and compared to that of EC-SOD C combined with catalase (CAT) and to that of CAT alone. EC-SOD C binds to heparan sulphate proteoglycan on the cell surfaces. Thirty-two pigs were subjected to 45 min of myocardial ischemia followed by 4 h of reperfusion. Control pigs (group A; n = 8) received 300 mL of saline into the great cardiac vein during a 30-min period started 5 min prior to reperfusion; pigs in group B (EC-SOD C; n = 8) got 16.6 mg of EC-SOD C; pigs in group C (EC-SOD C + CAT; n = 8) got 16.6 mg of EC-SOD C together with 150 mg of CAT. Pigs in group D (CAT; n = 8) received 150 mg of CAT. In groups B, C, and D, the drug was dissolved in saline and infused into the great cardiac. Infarct size expressed as percent of area at risk was smaller in groups B (14.5 +/- 16.7%) and C (40.8 +/- 13.3%) than in groups A (78.8 +/- 8.6%) and D (67.2 +/- 18.6%; p less than .05). Creatine kinase (CK) activity in ischemic myocardium was higher in groups B (1740 +/- 548 U/g) and C (1729 +/- 358 U/g) than in groups A (1184 +/- 237 U/g) and D (1251 +/- 434 U/g; p less than .05). There was an inverse relation (r = -.83) between infarct size and CK content. The EC-SOD C infusions resulted in only minimal increases in plasma SOD activities. In conclusion, the presence of SOD on the cell surfaces is of importance in the prevention of reperfusion injury rather than circulating SOD.
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PMID:Effects of recombinant human extracellular-superoxide dismutase type C on myocardial infarct size in pigs. 150 79

Oxygen free radicals are generated during reperfusion of ischemic organs. Studies employing several species of laboratory animal (rat, dog, pig, rabbit, mouse) have documented protective effects of a variety of free-radical scavengers and antioxidants when administered before or immediately preceding reperfusion of ischemic kidneys. These protective agents include superoxide dismutase, dimethylthiorea, dimethyl sulfoxide, alpha-tocopherol, glutathione, the iron chelator deferoxamine, probucol, allopurinol and oxypurinol, and the spin-trapping agent PBN. Furthermore, deficiency of antioxidants (selenium, alpha-tocopherol, or catalase) exacerbates postischemic renal injury. These findings have been applied to renal transplantation in an attempt to decrease the incidence of posttransplantation acute renal failure. This is important because acute renal failure results in morbidity, increases hospital stay and the cost of transplantation, and complicates the use of cyclosporine. In porcine and in canine kidney transplantation, superoxide dismutase and allopurinol have provided renal protection. Transplantation is complicated because there may be prolonged hypoperfusion before harvesting plus a brief period of total ischemia during harvesting, followed by a prolonged period of cold ischemia and/or reperfusion, then followed by another brief period of ischemia and reperfusion during transplantation. Injury may occur at each of these phases by different mechanisms.
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PMID:Free radical-mediated postischemic injury in renal transplantation. 150 58

This study was designed to test the hypothesis that the oxygen free radical scavengers superoxide dismutase (SOD) and catalase may reduce myocardial "stunning" after exercise-induced ischemia. To test this hypothesis, 8 mongrel dogs performed treadmill exercise for 10 min in the presence of a flow-limiting coronary artery stenosis. Regional left ventricular function was measured with ultrasonic microcrystals implanted to measure regional wall thickening. Regional myocardial perfusion was measured with radioactive microspheres. The combination of SOD (5 mg/kg iv) and catalase (5 mg/kg iv) did not affect heart rate, blood pressure, coronary artery flow, or regional myocardial blood flow at rest, during exercise, or in the postexercise period. SOD and catalase had no effect on regional wall thickening at rest before exercise. During exercise in the absence of a coronary artery stenosis, thickening was slightly lower during SOD and catalase infusion (27 +/- 11.0 vs. 30.8 +/- 11.5%, SOD vs. control P = 0.05). During exercise in the presence of a coronary artery stenosis, there was no difference in thickening. Infusion of SOD and catalase affected neither the transient rebound function occurring early after exercise nor the prolonged period of stunning. These results indicate that the myocardial stunning that follows exercise-induced ischemia is unlikely to be mediated by oxygen free radicals.
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PMID:Effect of superoxide dismutase and catalase on regional dysfunction after exercise-induced ischemia. 151 Jan 36

During the procedure of coronary artery bypass graft surgery (CABG), the release of free oxygen radicals as a result of ischemia and reperfusion which plants the seeds of post-operative low cardiac output and arrhythmias has grave consequence on the reestablishment of cardiac function. A variety of chemical agents such as mannitol, allopurinol, catalase (Q-10) and superoxide dismutase (SOD) has proved to be considerably effective to improve the myocardial necrosis following ischemia and reperfusion. In this study we chose mannitol (0.2 gm/kg) as the free oxygen radicals scavenger and utilized mass spectrophotometric method to detect the variation of concentration of [H2O2], a by-product of free oxygen radical, in an attempt to evaluate the efficacy of mannitol in this regard in patients undergoing CABG. Patients were divided into experimental group (n = 19) and control group (n = 20). In the experimental group the concentration of [H2O2] changed from 61 +/- 24 microM/L pre-operatively to 77 +/- 18 microM/L post-operatively as against 75 +/- 31 microM/L and 99 +/- 31 microM/L respectively in the control group. In comparison, only the change in experimental group was statistically significant (p less than 0.05). We confirmed that mannitol functions considerably as a free oxygen radical scavenger since it reduces the production of [H2O2] in patients undergoing CABG.
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PMID:[Mannitol reduces plasma hydrogen peroxide free radical in patients undergoing coronary artery bypass graft surgery]. 152 1

To clarify the role of oxygen radicals in the development of myocardial injury during ischemia, production of lipid peroxides mediated by oxygen radicals was determined in in vivo dogs subjected to regional ischemia and reperfusion. Myocardial injury was assessed by derangement in energy and carbohydrate metabolism caused by ischemia and reperfusion. The production of lipid peroxides mediated by oxygen radicals considerably increased not only during reperfusion after ischemia but also during ischemia. Removal of oxygen radicals by administration of radical scavengers [recombinant human superoxide dismutase + catalase or N-(2-mercaptopropionyl)glycine] completely prevented the increase in production of lipid peroxides during ischemia. However, the radical scavengers did not attenuate the myocardial energy and carbohydrate metabolic derangements caused by ischemia and reperfusion after ischemia. These results suggest that significant amounts of oxygen radicals are generated during ischemia as well as during reperfusion and that the oxygen radicals and subsequent lipid peroxidation are not major factors in development of myocardial injury during either ischemia or reperfusion after ischemia.
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PMID:Role of oxygen radicals in canine myocardial metabolic derangement during regional ischemia. 153 15

Preconditioning the heart with 5 min of ischemia renders the heart very resistant to infarction from subsequent ischemia by an unknown mechanism. We investigated whether the protective effect of preconditioning might be related to an increase in rabbit heart antioxidant defenses. The antioxidant activities of catalase, glutathione peroxidase, Mn superoxide dismutase, Cu,Zn superoxide dismutase, glucose-6-phosphate dehydrogenase, glutathione reductase, and total glutathione were measured in ischemic and normal regions from both control and preconditioned rabbit hearts. All hearts experienced 30 min regional ischemia and 5 min reperfusion. None of the antioxidant enzymes changed in activity when comparing nonischemic and postischemic zones in either nonpreconditioned or preconditioned hearts. Total glutathione, however, was reduced in reperfused zones and showed better preservation in preconditioned hearts. To determine whether this preservation resulted from a higher value at the onset of reperfusion or slower washout during reperfusion, we analyzed a second group of nonreperfused hearts after 30 min ischemia. The hearts had normal glutathione content in both ischemic and nonischemic zones of either preconditioned or control hearts. The most likely explanation is that preconditioned hearts experienced less washout of glutathione simply because they were less injured. We therefore conclude that enhancement of antioxidant defenses is not the mechanism of preconditioning.
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PMID:Protection from reperfusion injury by preconditioning hearts does not involve increased antioxidant defenses. 153 19

Exogenously supplied catalase, a peroxisomal enzyme, has been found to be of therapeutic value in ischemic injury. Therefore, we examined the effect of ischemic-reperfusion injury on the structure and function of kidney peroxisomes. Ischemic injury changed the density of peroxisomes from 1.21 g/cm3 (peak I) to a lighter density of 1.14 g/cm3 (peak II). The number of peroxisomes moving from the normal density population (peak I) to a lower density population (peak II) increased with an increase in ischemic injury. Latency experiments indicated both populations of peroxisomes to be of intact peroxisomes. Immunoblot analysis with antibodies against peroxisomal matrix and membrane proteins demonstrated that after 90 min of ischemia a significant number of matrix proteins were lost in the peak II population, suggesting that functions of these peroxisomes may be severally affected. Reperfusion following ischemic injury resulted in loss of peroxisomal matrix proteins in both peaks I and II, suggesting that peroxisomal functions may be drastically compromised. This change in peroxisomal functions is reflected by a significant decrease in peroxisomal catalase activity (35%) and beta-oxidation of lignoceric acid (43%) observed following 90 min of ischemia. The decrease in catalase activity was more pronounced in reperfused kidneys even after a shorter term of ischemic injury. Reperfusion restored the normal peroxisomal beta-oxidation in kidneys exposed up to 60 min of ischemia. However, 90 min of ischemia was irreversible as there was a further decrease in beta-oxidation upon reperfusion. The decrease in catalase activity during ischemia alone was due to the formation of an inactive complex, whereas during reperfusion, following 90 min of ischemia, inactivation and proteolysis or decreased synthesis of catalase contributed equally toward the injury. The observed changes in the structure and function of peroxisomes as a result of ischemic-reperfusion injury and the ubiquitous distribution of peroxisomes underlines the importance of this organelle in the pathophysiology of vascular injury in general.
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PMID:Ischemia-reperfusion injury: biochemical alterations in peroxisomes of rat kidney. 157 21

We studied the concomitant effects of scavengers of reactive oxygen species (ROS) on both cardiac function and the incidence of arrhythmias. Isolated rat heart was perfused with a working mode paced at 300 beats/min. The left coronary artery was occluded for 5, 7, 15, or 60 min and reperfused thereafter for 30 min. Superoxide dismutase and catalase were infused from 5 min prior to reperfusion to the end of reperfusion in the scavenger treatment group. In the 60-min ischemia group with scavenger treatment, the cardiac output was significantly higher than that in the untreated group at both 10 and 30 min of reperfusion (P less than 0.01). In the 15-min ischemia group with scavenger treatment, the cardiac output showed a tendency toward a higher value than that in the untreated group. The incidence of reperfusion arrhythmias occurring after a short ischemic time (5, 7, or 15 min) were similar in the scavenger treated and untreated groups; but, with a preceding ischemia of 60 min, the incidence of ventricular tachycardia was higher in the scavenger treated group than in the untreated group (P less than 0.02). In conclusion, scavengers improved contractile dysfunction but did not attenuate the incidence of arrhythmias.
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PMID:The failure of radical scavengers to attenuate the incidence of reperfusion arrhythmias despite improvement of cardiac function. 158 9

An experimental model of optic nerve ischemia was designed in the rabbit to determine early biochemical alterations, i.e.--changes of high energy phosphate metabolites (ATP and phosphocreatine)--in occlusive and peri-occlusive areas. Vascular occlusion provoked a rapid fall of ATP and phosphocreatine in the optic nerve. Free radicals scavengers, superoxide dismutase plus catalase or dimethylthiourea were able to counteract the drop of phosphate metabolites in the peri-occlusive area. These results show that hypoxia leads to oxygen-derived free radical generation which can be responsible for cell damage and emphasize the role of free radicals in the pathogenesis of ocular diseases related to vascular dysfunction.
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PMID:Alterations of energetic metabolite levels by free radicals during optic nerve ischemia. 158 50

To determine the contribution of oxygen-derived free radicals to the changes in microvascular structure and function which follow reperfusion of ischemic myocardium, isolated perfused rat hearts were subjected to 15 or 45 min of global ischemia followed by 5 min of oxygenated reperfusion. Hearts were then fixed by perfusion with glutaraldehyde and perfused with nuclear track photographic emulsion to identify competent capillaries in scanning and transmission electron micrographs. Reperfusion after 15 min caused a significant reduction in the density of competent capillaries in the subendocardial third of the left ventricle, but this reduction was lessened but not eliminated by the addition of 0.61 mmole/liter desferrioxamine, but not by 60,000 U/liter superoxide dismutase plus 60,000 U/liter catalase, to the perfusate. After 45 min of ischemia both interventions prevented the myocyte swelling, endothelial cell changes, bleb formation, and reduction in microvascular lumina characteristic of unprotected reperfusion, but only desferrioxamine significantly improved microvascular competence. This suggests that the hydroxyl radical rather than superoxide and/or hydrogen peroxide has a pathogenic role, although desferrioxamine may have other effects as nonspecific chelator. Postischemic reductions in capillary function also occur in reversibly injured myocardium in the absence of structural abnormality. Preventing postischemic microvascular incompetence has the potential to minimize ischemic cell injury and to enhance repair following myocardial infarction, but it also may increase the risk of hemorrhage from venules.
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PMID:Anti-oxidant therapy improves microvascular ultrastructure and perfusion in postischemic myocardium. 163 71


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