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

This study evaluated the effects of a prostaglandin I2 analogue (aPGI2), superoxide dismutase (SOD), and catalase (CAT) on hepatic injury after warm ischemia and reperfusion in terms of survival, mitochondrial function, serum enzymes, and histology. Hepatic ischemia was created in rats by clamping the hepatoduodenal ligament for 90 min with splenofemoral bypass. Reperfusion was induced by unclamping the vessels and disconnecting the splenofemoral bypass. Then aPGI2 (350 ng/kg/min) was infused for 60 min just before hepatic ischemia, and SOD and CAT (5,000 units/kg each) were administered immediately before the start of reperfusion. Serum enzyme and mitochondrial function assessments of livers were made just after ischemia, and after 2 hr of reperfusion. Survival rate was also assessed in a separate group of rats. Liver enzymes such as SGOT, SGPT, and LDH showed no correlation to liver viability. The administration of aPGI2 alone showed no effect on ischemically injured mitochondria; however, the free radical scavengers (SOD, CAT), in combination with aPGI2, showed significant improvement of mitochondrial function together with extension of survival. The ultrastructure of hepatocytes was better preserved in the treated groups. These agents improved the viability of ischemic-reperfused injured livers.
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PMID:Effects of prostaglandin I2, superoxide dismutase, and catalase on ischemia-reperfusion injury in liver transplantation. 225 62

Oxygen free radicals (OFRs) generated during reperfusion are putative mediators of postischemic renal dysfunction. To address this issue, the renal response to ischemia and reperfusion was compared to the response to OFR generation without ischemia. Isolated rat kidneys were perfused at 37 degrees C and 90-100 mm Hg with an asanguinous modified Krebs' buffer. Kidneys were subjected to 30 min of ischemia followed by reperfusion or to OFRs generated by combining 25 mumole hypoxanthine with 1 unit xanthine oxidase. Both insults caused a 50% increase in vascular resistance. This was accompanied by a 30% reduction in perfusate flow rate and an 80% reduction in glomerular filtration and urine flow rates. The OFR scavengers, superoxide dismutase (SOD, 250 units/ml) and catalase (CAT, 500 units/ml), prevented these alterations after OFR generation but not after 30 min of ischemia and reperfusion. SOD and CAT also afforded no protection against the less severe dysfunction observed after 10 or 20 min of ischemia and reperfusion. OFRs do not appear to be prominent mediators of postischemic renal dysfunction; other factors, probably associated with ischemia must be primarily responsible.
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PMID:Postischemic renal dysfunction: the limited role of xanthine oxidase-generated oxygen free radicals. 226 85

The effects of infusing superoxide dismutase (SOD) and catalase (CAT) into the coronary circulation were investigated in isolated, working rat hearts prior to and during a 15 minute episode of regional ischemia followed by 30 minutes reperfusion. Aortic output, left ventricular pressure and dP/dT were recorded. Compared to untreated hearts, SOD and CAT significantly improved function during reperfusion, but had no effect during the pre-ischemic or the ischemic period. To investigate possible transport of SOD and CAT into rat myocytes, cryotome sections of isolated, Langendorff perfused rat hearts were exposed to rabbit antibody prepared against the exogenous SOD and CAT. Bound antibody was detected by the indirect-fluorescent antibody test. The interior of myocytes from rat hearts exposed to SOD and CAT bound antibodies prepared against these enzymes, whereas myocytes from rat hearts not exposed to exogenous SOD and CAT only bound the CAT antibodies. This indicates the anti-SOD we prepared is specific for exogenous SOD, and also suggests exogenous SOD can gain access to the cytoplasm of myocytes from the coronary circulation.
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PMID:Exogenous superoxide dismutase and catalase promote recovery of function in isolated rat heart after regional ischemia and may be transported from capillaries into myocytes. 227 50

Blood granulocyte-mediated reactions involving generation of oxygen-derived free radicals have recently been shown to be capable of causing injury to the lungs. These findings suggest a similar mechanism also to be involved in the development of pulmonary ischemia/reperfusion injury. In the present study, therefore, the effects of three oxygen-derived free radical scavengers, superoxide dismutase (SOD; 1 mg/kg), catalase (20,000 IU/kg) and allopurinol (45 mg/kg), were evaluated during reperfusion in a rabbit model after 2 h normothermic ischemia of the lung. During reperfusion, ischemic lungs were found to have an elevated pulmonary vascular resistance, increased total and extravascular lung water content, and decreased arterial oxygen tension (PaO2) compared to control animals. SOD and catalase, but not allopurinol, were able to reduce pulmonary injury by lowering the pulmonary vascular resistance, but could not prevent pulmonary damage as shown by total lung water (TLW) or PaO2. It is concluded that oxygen-derived free radicals such as hydrogen peroxide and the superoxide anion may play an important role in precipitating pulmonary injury after ischemia. The failure of xanthine oxidase inhibition (allopurinol) to exert protective effects may suggest that oxygen-derived free radical generation following pulmonary ischemia occurs predominantly via leukocyte-mediated reactions.
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PMID:Pulmonary reperfusion injury: evidence for oxygen-derived free radical mediated damage and effects of different free radical scavengers. 228 47

Severe experimental hypertension is associated with vascular hyperpermeability and cellular damage in small arteries and arterioles in rats. Oxygen-derived free radical production is also associated with increased vascular permeability and cellular injury in a variety of conditions, including ischemia-reperfusion and inflammation. To determine if free radicals play a role in the pathogenesis of hypertensive vascular disease, the free radical scavengers superoxide dismutase (SOD), catalase, SOD and catalase, and dimethyl sulfoxide (DMSO) were given to rats made acutely hypertensive with angiotensin II infusions. Untreated hypertensive and normotensive control animals were used for comparison. The effects of scavenger treatment were assessed by in vivo observations of intestinal small arteries by use of stereomicroscopy and videotape and light and transmission electron microscopy to identify and quantitate vascular lesions, and tracer particle injections to determine permeability changes. In vivo observations revealed that scavenger treatment did not alter vascular constriction patterns, vessel caliber, or blood pressures. Electron microscopy of arteries from untreated hypertensive rats showed more severe and more extensive endothelial and smooth muscle lesions, increased tracer particle penetration, and greater fibrin deposition than that found in scavenger-treated hypertensive groups. Quantitation of vascular lesions showed approximately equal reductions in smooth muscle necrosis (p less than 0.01) and fibrin deposition (p less than 0.05) in arteries from each of the scavenger-treated hypertensive groups. The results indicate that the free radical scavengers SOD, catalase, SOD-catalase, and DMSO inhibit (but do not prevent) vascular hyperpermeability and cellular damage during acute, angiotensin II--induced hypertension. These findings suggest that free radicals play a role in the pathogenesis of hypertensive vascular disease, probably by exacerbating the vascular changes initially triggered by an acute elevation in blood pressure.
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PMID:Role of oxygen-derived free radicals in acute angiotensin II--induced hypertensive vascular disease in the rat. 230 4

Ischemia-reperfusion lung injury limits lung transplantation. Neutrophil activation and/or xanthine oxidase-mediated purine degradation may cause toxic oxygen metabolite production and lung injury. We investigated whether circulating blood elements are involved in the pathogenesis of ischemia-reperfusion lung injury. Isolated rat lungs were perfused with physiological salt solution (PSS) stabilized with Ficoll until circulating blood elements were not detected in the lung effluent. Lungs were then rendered ischemic by stopping ventilation and perfusion for 45 min at room temperature. Lung injury occurred and was quantitated by the accumulation of 125I-bovine serum albumin into lung parenchyma and alveolar lavage fluid during reperfusion. Lung injury occurred, in the absence of circulating blood elements, when ischemic lungs were reperfused with PSS-Ficoll solution alone. Reperfusion with whole blood or PSS-Ficoll supplemented with human or rat neutrophils did not increase lung injury. Furthermore, during lung ischemia, the presence of neutrophils did not enhance injury. Experiments using PSS-albumin perfusate and quantitating lung injury by permeability-surface area product yielded similar results. Microvascular pressures were not different and could not account for the results. Toxic O2 metabolites were involved in the injury because addition of erythrocytes or catalase to the perfusate attenuated the injury. Thus reperfusion after lung ischemia causes injury that is dependent on a nonneutrophil source of toxic O2 metabolites.
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PMID:Neutrophils are not necessary for induction of ischemia-reperfusion lung injury. 231 80

Neutrophils have been implicated in the genesis of myocardial ischemia-reperfusion injury, and their mechanism of action has been linked to the production of reactive oxygen species, fatty acid-derived prostanoids, and leukotrienes. In this study, we examined the potential relation between production of reactive oxygen species and cyclooxygenase-derived autacoids by studying the effects of superoxide dismutase (SOD) and catalase (CAT) on the rise in thromboxane formation observed with myocardial ischemia and reperfusion. Immunoreactive thromboxane B2 was measured in cardiac lymph from conscious dogs during reperfusion after a 60-minute occlusion in the presence of infusions of SOD alone, CAT alone, and a combination of SOD and CAT. Reperfusion after 60 minutes of ischemia causes an immediate elevation in thromboxane B2. SOD and CAT infusion prevented this rise in thromboxane B2 as did infusion of SOD alone. The ability of SOD-CAT to suppress thromboxane B2 production dissipated within 3 hours after the cessation of infusion, at which time thromboxane B2 excretion increased. The modulation of fatty acid oxygenases by reactive oxygen species may be a very important pathogenic factor in considering the origin of the protective effect of antioxidants in the setting of myocardial ischemia-reperfusion injury.
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PMID:Thromboxane B2 in cardiac lymph. Effect of superoxide dismutase and catalase during myocardial ischemia and reperfusion. 231 86

Contractile dysfunction of viable, previously ischemic stunned myocardium is thought to be due to reactive oxygen species generated during ischemia/reperfusion. Direct in vivo evidence that oxidants cause systolic or diastolic dysfunction of viable myocardium has, however, been lacking. We sought to determine whether in vivo exposure of canine myocardium to exogenously generated reactive oxygen species could--in the absence of myocardial ischemia or necrosis--"mimic" the depressed systolic contractile function, paradoxical contraction during early diastole, and prolonged diastolic relaxation time characteristic of stunned myocardium. Anesthetized open-chest dogs were randomly assigned to receive either (1) the free radical generating substrates xanthine oxidase + purine + iron-saturated transferrin or (2) saline, infused directly into an anterior coronary vein. Infusion of free radical substrates did not cause ischemia: regional myocardial blood flow and myocardial high-energy phosphate stores were normal in both groups. Furthermore, infusion of xanthine oxidase + purine + transferrin was not associated with histologic or electron microscopic evidence of myocyte injury or death in this model. Xanthine oxidase + purine + transferrin did, however, produce marked abnormalities in regional systolic contractile function; at 2 hours after the onset of infusion, segment shortening (assessed by sonomicrometry) in the perfused region of the heart averaged 62 +/- 5% of baseline, preinfusion values in animals infused with free radical substrates versus 113 +/- 8% of baseline values in saline-administered control dogs (p less than 0.004). This systolic dysfunction was effectively reversed by administration of the free radical scavenging agents superoxide dismutase + catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo infusion of oxygen free radical substrates causes myocardial systolic, but not diastolic dysfunction. 232 2

Hydrogen peroxide (H2O2) has been implicated in cardiac damage due to ischemia and reperfusion. We adapted an electron microscopic, histochemical method for demonstrating H2O2 produced by isolated cells to isolated, buffer-perfused rabbit hearts. The method involves formation of an electron-dense precipitate when H2O2 reacts with cerium chloride (CeCl3). We perfused hearts retrograde via the aorta with well-oxygenated bicarbonate-buffered solution, followed by one in which bicarbonate was replaced with imidazole (IPSS) to prevent precipitation of bicarbonate and CeCl3. Some hearts were made globally ischemic (30 min, 37 degrees C), reperfused 5 min with well-oxygenated IPSS containing 1 mM CeCl3, then processed for electron microscopy. Others were perfused with IPSS containing catalase (300 U/ml) or albumin before ischemia and upon reperfusion, followed by CeCl3 administration. Nonischemic control hearts perfused with IPSS (+/- catalase) were also studied. Electron micrographs were assessed visually and by computer for precipitate localization and amount. There was abundant precipitate on the luminal face of the coronary vascular endothelium in ischemic-reperfused, cerium-treated hearts, including those treated with albumin. There was significantly less in reperfused catalase-treated or nonischemic control hearts. X-ray microbeam analysis of the endothelial precipitate indicated the presence of Ce. This appears to be the first visual demonstration of a CeCl3-H2O2-dependent reaction product in intact isolated ischemic hearts. The data indicate that at the time of reperfusion some H2O2 is accessible to the vascular space, and that its amount can be reduced by perfused catalase. Further modifications this technique may be useful for assessing the sites and pathways by which H2O2 is generated by hearts or other buffer-perfused organs subjected to stresses such as ischemia or hypoxia.
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PMID:Cerium chloride as a histochemical marker of hydrogen peroxide in reperfused ischemic hearts. 232 33

The role of superoxide and lipid peroxidation in liver injury induced by ischemia-reperfusion was investigated in rats. Ischemic condition of the liver was created by applying small clamps to the right branch of portal vein and the right hepatic artery for 15 min. Clamping of hepatic artery and portal vein could decrease the hepatic blood flow to about 30% of that measured before the clamping. Levels of serum GPT and thiobarbituric acid (TBA) reactive substances in the liver tissue were significantly increased 30 min after the reperfusion following 15 min of ischemia. The increase in serum GPT and TBA reactants in the liver tissue was significantly inhibited by the treatment with superoxide dismutase combined with catalase. The treatment with allopurinol significantly inhibited the elevation of serum GPT levels and showed a tendency to inhibit the increase in TBA reactants in liver tissue. These results suggest that active oxygen species and lipid peroxidation may play an important role in the pathogenesis of ischemia-reperfusion injury in the liver, and hypoxanthine-xanthine oxidase system may be one of the main sources of active oxygen species.
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PMID:[Role of active oxygen species and lipid peroxidation in liver injury induced by ischemia-reperfusion]. 232 99


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