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)

Free radicals have been implicated in the damage caused by tissue ischemia and reperfusion. Canine kidneys were subjected to a 60-minute period of normothermic ischemia. One group of animals received intra-arterial superoxide dismutase (SOD, 17.6 mg/50 ml, 50,000 units) at the end of the ischemic period, whereas a second group received albumin (17.6 mg/50 ml). The kidneys treated with SOD demonstrated significantly less edema formation (1.0 +/- 0.3% wet weight vs. 1.8 +/- 0.2%, mean +/- SEM, p less than 0.05) and lower renovascular resistance (44.0 +/- 5.6 dynes-sec/cm5 vs. 64.0 +/- 12.0, p less than 0.05). The SOD group displayed greater preservation of both glomerular filtration rate (45.9 +/- 6.1% of baseline vs. 23.7 +/- 5.8%, p less than 0.05) and urine flow (1.3 +/- 0.4 ml/min vs. 0.3 +/- 0.1, p less than 0.05). We conclude that the free radical scavenger SOD provides significant protection of the kidney during ischemia and reperfusion.
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PMID:Protection of the kidney after temporary ischemia: free radical scavengers. 396 59

Reperfusion after reversible regional ischemia has been shown to result in delayed recovery of myocardial function, but the mechanism responsible for this phenomenon remains unknown. We explored the potential role of oxygen-free radicals as mediators of postischemic dysfunction in open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery (LAD) followed by 2 hr of reperfusion. Treated animals (n = 19) received an infusion of the oxygen free-radical scavengers superoxide dismutase (SOD; 15,000 U/kg) and catalase (CAT; 55,000 U/kg) for 1 hr starting 15 min before LAD occlusion, while control animals (n = 20) received an equal volume of saline. SOD and CAT produced no discernible effect on heart rate, aortic pressure, or left atrial pressure. Collateral flow to the ischemic zone (radioactive microspheres) was 0.07 +/- 0.01 ml/min/g in both groups. The size of the occluded bed as determined by postmortem perfusion was 26.1 +/- 1.2% of the left ventricle in the control group and 26.5 +/- 0.9% in the treated group. Systolic wall thickening (an index of regional function) was assessed with an epicardial pulsed-Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesia during ischemia. Nevertheless, recovery of function (expressed as percent of baseline) was considerably greater in the treated dogs, both at 1 hr (43.8 +/- 14.3 vs 12.8 +/- 11.6) and 2 hr of reperfusion (74.2 +/- 8.4 vs 31.6 +/- 9.8, p less than .005). This improved recovery of function obtained with SOD and CAT suggests that oxygen-free radicals play an important role in the genesis of myocardial dysfunction after a brief episode of regional ischemia.
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PMID:Enhancement of recovery of myocardial function by oxygen free-radical scavengers after reversible regional ischemia. 402 84

The activity of the free radical scavenger, superoxide dismutase, was studied in focal cerebral ischemia produced in Mongolian gerbils (Meriones unguiculatus) by occluding the right common and left external carotid arteries under halothane anesthesia. After recovery from anesthesia animals were classified according to their neurologic symptoms. Five animals exhibiting neurologic symptoms such as hemiparesis and rolling seizures were reanesthetized 120 min after vascular occlusion and their brains frozen in situ with liquid nitrogen. A series of 20-micron-thick coronal sections was cut in a cryostat; pictorial representations of tissue pH, ATP, and glucose were obtained using fluorescent and bioluminescent techniques. Using a highly sensitive bioluminescent technique, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and Mn-superoxide dismutase (Mn-SOD) activities were then measured in samples from both ischemic and nonischemic regions of the remaining tissue block. Cu,Zn-SOD and Mn-SOD activities were, respectively, 13.9 +/- 0.7 X 10(3) units/g and 5.4 +/- 0.3 X 10(3) units/g in the nonischemic tissue, and 13.2 +/- 0.6 X 10(3) units/g and 5.0 +/- 0.2 X 10(3) units/g within the ischemic tissue. Thus focal cerebral ischemia does not lead to a global decrease in SOD activity, as observed by others after heart and liver ischemia.
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PMID:Superoxide dismutase activity in experimental focal cerebral ischemia. 406 77

The efficacy of preventing ischemia-reperfusion damage by employing native or modified (mPEG-SOD) superoxide dismutase in an experimental animal model of acute ischemia of the left hindlimb was tested. Four hours and thirty minutes complete warm ischemia was induced in the left hindlimb of 43 Wistar rats, by clamping the femoral artery and monitoring its efficacy with Laser Doppler flowmetry. After ten days, a significative difference (p = 0.004) of the survival leg rate was found in the group treated with mPEG-SOD (86.6%) compared with the control group (30%). Histomorphological and ultrastructural analysis were performed at different time intervals confirming what the clinical course had already pointed out. These results show that SOD in its modified form, despite the lower dosage, can provide good protection against ischemia/reperfusion injury of muscles.
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PMID:Biopolymeric modification of superoxide dismutase (mPEG-SOD) to prevent muscular ischemia-reperfusion damage. 749 20

Nitric oxide (NO) is a novel biologic messenger with diverse effects but its role in organ transplantation remains poorly understood. Using a porphyrinic microsensor, the first direct measurements of coronary vascular and endocardial NO production were made. NO was measured directly in the effluent of preserved, heterotopically transplanted rat hearts stimulated with L-arginine and bradykinin; NO concentrations fell from 2.1 +/- 0.4 microM for freshly explanted hearts to 0.7 +/- 0.2 and 0.2 +/- 0.08 microM for hearts preserved for 19 and 38 h, respectively. NO levels were increased by SOD, suggesting a role for superoxide-mediated destruction of NO. Consistent with these data, addition of the NO donor nitroglycerin (NTG) to a balanced salt preservation solution enhanced graft survival in a time- and dose-dependent manner, with 92% of hearts supplemented with NTG surviving 12 h of preservation versus only 17% in its absence. NTG similarly enhanced preservation of hearts stored in University of Wisconsin solution, the clinical standard for preservation. Other stimulators of the NO pathway, including nitroprusside, L-arginine, or 8-bromoguanosine 3',5' monophosphate, also enhanced graft survival, whereas the competitive NO synthase antagonist NG-monomethyl-L-arginine was associated with poor preservation. Likely mechanisms whereby supplementation of the NO pathway enhanced preservation included increased blood flow to the reperfused graft and decreased graft leukostasis. NO was also measured in endothelial cells subjected to hypoxia/reoxygenation and detected based on its ability to inhibit thrombin-mediated platelet aggregation and serotonin release. NO became undetectable in endothelial cells exposed to hypoxia followed by reoxygenation and was restored to normoxic levels on addition of SOD. These studies suggest that the NO pathway fails during preservation/transplantation because of formation of oxygen free radicals during reperfusion, which quench available NO. Augmentation of NO/cGMP-dependent mechanisms enhances vascular function after ischemia and reperfusion and provides a new strategy for transplantation of vascular organs.
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PMID:Cardiac preservation is enhanced in a heterotopic rat transplant model by supplementing the nitric oxide pathway. 751 95

The cardioprotective effects of human recombinant extracellular-superoxide dismutase type C (hr-EC-SOD C) were compared with those of bovine Cu,Zn-SOD in isolated working rat heart subjected to 35-min global normothermic ischemia followed by 55-min reperfusion. hr-EC-SOD C or bovine Cu,Zn-SOD (3 x 10(4) and 6 x 10(4) IU/L, respectively) was added to St. Thomas' Hospital (STH) cardioplegic solution infused 5 min before and 10 min after the ischemic period. Control hearts were treated with STH cardioplegic solution without SOD. By the end of reperfusion, hr-EC-SOD C-treated hearts recovered left ventricular systolic pressure (LVSP), aortic flow (AF) and cardiac output (CO) to 95 +/- 4, 60 +/- 4, 69 +/- 6% of preischemic value, respectively, as compared with 86 +/- 3, 44 +/- 5, and 52 +/- 6% in the control (p < 0.05). Cardioplegia with hr-EC-SOD C significantly reduced lactate dehydrogenase (LDH) release into myocardial effluent during reperfusion (p < 0.05) and increased ATP, AMP, and total creatine (Cr) tissue contents in reperfused hearts (by 21 +/- 3, 42 +/- 4, and 34 +/- 3%, respectively, as compared with control hearts, p < 0.05). The effects of bovine SOD on functional and biochemical indexes were similar but not statistically significant as compared with control. Treatment with hr-EC-SOD C, but not with bovine SOD, resulted in reduction in hydroxyl radical formation assessed by 5-5-dimethy-1-pyrroline-N-oxide spin trap (DMPO) in coronary effluent at early reperfusion with electron spin resonance (ESR) technique. The results suggest that enhanced myocardial protection against ischemia/reperfusion injury afforded by hr-EC-SOD C is related to scavenging of oxygen-derived free radicals.
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PMID:Human recombinant extracellular-superoxide dismutase type C improves cardioplegic protection against ischemia/reperfusion injury in isolated rat heart. 752 49

Reperfusion after ischemia results in endothelial cell injury and Kupffer cell activation. Inflammatory cytokines thus released can induce major histocompatibility complex antigens and increase the immunogenecity of the graft. An orthotopic rat liver allotransplant model was used to test the hypothesis that prevention of reperfusion injury by infusion of polyethylene glycol superoxide dismutase (PEG-SOD) would result in long-term allograft survival in the presence of subthreshold immunosuppressive dosages. ACI rats were used as donors, and Lewis strain rats as recipients. Orthotopic liver transplantation was initially performed to identify a subthreshold dose of the immunosuppressant FK-506, which would be unable to extend survival longer than control untreated rats with this strain combination. After testing three intramuscular FK-506 doses of 0.04, 0.08, and 0.16 mg/kg, it was observed that an FK-506 dose of 0.04 mg/kg/day for 14 days was unable to extend survival longer than in untreated recipients. This dose of FK-506 was used in combination with PEG-SOD at doses of 1000, 3000, 10,000, or 30,000 units. Recipient animals were treated intravenously with PEG-SOD as a loading dose to facilitate tissue penetration on day 1, and beginning on the day of transplantation, every 2 days for the duration of the study. Results of histologic studies and mean survival time were compared in untreated recipients and in rats treated with PEG-SOD plus 0.04 mg/kg/day FK-506.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction of FK-506 requirements by combination with polyethylene glycol superoxide dismutase in orthotopic rat liver transplantation. 754 Oct 60

In this study, the kinetics of copper-zinc superoxide dismutase (CuZn-SOD) in experimentally induced ischemia-reperfusion injury of the canine jejunum were examined using immunohistochemical procedures, and evaluated as an index for the viability of transplants. A pedicled jejunal graft was subjected to arterial reperfusion after clamping the supplying blood vessels for 30 min. Under nonischemic conditions, some of the goblets in the goblet cells and the mucin covering the surface of the villi were stained positively with luxol fast blue, von Kossa, and immunohistochemistry for CuZn-SOD. Between 5 and 30 min after reperfusion, the appearance of goblets with positive immunoreaction for CuZn-SOD in the intestinal glands and the disappearance of these goblets in the villi were observed in the grafts of animals that received arterial reperfusion after 30 min of clamping of the arteries and veins at room temperature. Thereafter, the former disappeared gradually and the latter returned toward the nonischemic condition. The administration of allopurinol led to a decrease in tissue damage and a significantly higher number of goblets with positive immunoreaction for CuZn-SOD than in untreated animals. Furthermore, the goblets in the intestinal glands showed a negative reaction for CuZn-SOD 5 to 30 min after reperfusion. Preservation at 4 degrees C during ischemia revealed similar results to those observed in the animals given allopurinol. Thus, the distribution and intensity of CuZn-SOD positive goblets seems to be a useful indicator for the evaluation of tissue damage induced by free radicals mediating ischemia-reperfusion injury.
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PMID:The kinetics of copper-zinc superoxide dismutase in experimentally induced ischemia-reperfusion injury of the canine jejunum. 763 26

Intravital video microscopy was used to test superoxide dismutase and a lazaroid analogue, U-74389F, as a pretreatment for ischemia-reperfusion-induced microvascular dysfunction in skeletal muscle. Twenty-two male Wistar rats (350-400 g), anesthetized with sodium pentobarbital (65 mg/kg i.p.), were divided into groups to test the lazaroid analogue U-74389F (3 mg/kg; n = 8), a citric acid/citrate mixture (CS-4; n = 4) used as the vehicle for the lazaroid analogue, superoxide dismutase (SOD, 10 mg/kg; n = 5), and saline (n = 5). Normothermic ischemia of the extensor digitorum longus muscle was induced for 3 h by tightening a tourniquet placed around the limb above the muscle. Measurements of the number of perfused capillaries (CDper; mm-1) and capillary red blood cell velocity (VRBC; mm/s) were made after 30, 60 and 90 min of reperfusion. Thirty minutes following release of the tourniquet, all test groups showed a significant drop in CDper. The extent of this reduction was maximal in SOD treated muscles, while it was minimized in the lazaroid-treated muscles following 90 min reperfusion. Hyperemia occurred only in muscles treated with saline or lazaroid. The hyperemia was of limited duration in saline-treated muscles, but lasted the entire reperfusion period following lazaroid treatment. An index of microvascular flow, estimated from the product of VRBC and CDper, indicated that flow was significantly greater in muscles treated with lazaroids as compared with all other groups following the 90-min reperfusion. We conclude that whereas SOD was detrimental, the lazaroid analogue U-74389F improved microvascular perfusion following 3 h of no-flow ischemia and 90 min reperfusion.
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PMID:Effect of superoxide dismutase and 21-aminosteroids (lazaroids) on microvascular perfusion following ischemia-reperfusion in skeletal muscle. 763 46

A growing body of experimental data indicates that the "no-reflow" phenomenon is a type of reperfusion injury in skeletal muscle which may, in part, be mediated by oxygen free radicals, and thus may be attenuated by using agents that scavenge or inhibit formation of these reactive oxygen metabolites. This study was undertaken to assess the efficacy of recombinant human manganese superoxide dismutase (rhMnSOD) in reducing reperfusion injury in skeletal muscle. The specific advantage of this agent over other SOD types is a much longer plasma half-life (5 to 7 hr), allowing better equilibration between extra- and intracellular compartments. The rat cremaster model was used to study "no-reflow" in skeletal muscle. Reperfusion injury in the muscle was assessed by fluorescein dye perfusion, myocyte creatine phosphokinase (CPK) release, and contractile function in response to electrical field stimulation. Compared with untreated saline control animals, those treated with rhMnSOD after 5 hr of cremasteric ischemia, had a significantly higher percentage area of blood reflow (78 percent +/- 6 percent of normal), a greater percentage tetanic (66 percent +/- 9 percent of normal) and twitch (56 percent +/- 9 percent of normal) contractile strength, and less CPK release (21.5 percent higher than pre-reperfusion baseline CPK levels) (p < 0.05). Untreated saline control CPK release (21.5 percent higher than the prereperfusion level. Animals treated with allopurinol also had a significantly higher percentage twitch contraction (47 percent +/- 14 percent of normal) and a lower CPK release (11.1 percent of the prereperfusion value) 45 min after reperfusion than untreated saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy of recombinant human manganese superoxide dismutase compared to allopurinol in protection of ischemic skeletal muscle against "no-reflow". 765 Jun 47


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