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)

These experiments examined the independent effects of short-term exercise and heat stress on myocardial responses during in vivo ischemia-reperfusion (I/R). Female Sprague-Dawley rats (4 mo old) were randomly assigned to one of four experimental groups: 1) control, 2) 3 consecutive days of treadmill exercise [60 min/day at 60-70% maximal O2 uptake (VO2 max)], 3) 5 consecutive days of treadmill exercise (60 min/day at 60-70% VO2 max), and 4) whole body heat stress (15 min at 42 degrees C). Twenty-four hours after heat stress or exercise, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was maintained for 30-min followed by a 30-min period of reperfusion. Compared with control, both heat-stressed animals and exercised animals (3 and 5 days) maintained higher (P < 0.05) left ventricular developed pressure (LVDP), maximum rate of left ventricular pressure development (+dP/dt), and maximum rate of left ventricular pressure decline (-dP/dt) at all measurement periods during both ischemia and reperfusion. No differences existed between heat-stressed and exercise groups in LVDP, +dP/dt, and -dP/dt at any time during ischemia or reperfusion. Both heat stress and exercise resulted in an increase (P < 0.05) in the relative levels of left ventricular heat shock protein 72 (HSP72). Furthermore, exercise (3 and 5 days) increased (P < 0.05) myocardial glutathione levels and manganese superoxide dismutase activity. These data indicate that 3-5 consecutive days of exercise improves myocardial contractile performance during in vivo I/R and that this exercise-induced myocardial protection is associated with an increase in both myocardial HSP72 and cardiac antioxidant defenses.
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PMID:Short-term exercise improves myocardial tolerance to in vivo ischemia-reperfusion in the rat. 1164 63

Hemodynamic disorders in brain dead organ donors induce hypoxia, warm ischemia and finally tissue damage. A cold preservation period also induces tissue and cellular lesions. The two major modes of preservation are cold storage (CS) and hypothermic pulsatile perfusion (HPP). We aimed to compare the influence of each mode of preservation and their combination on oxidative stress, perfusion characteristics and tissue damage, after a period of warm ischemia. Rat kidneys which had undergone ischemia (0, 30, 60 min) were preserved either by CS (12, 24 h), or by HPP (12 h), or by a combination of both (HPP+CS, CS+HPP), in University of Wisconsin cold storage solution (UWCSS) at + 4 degrees C. During HPP, renal vascular pressure decreased then increased to reach 90 mmHg after perfusion for 7 h. If HPP followed CS, the mean pressure reached 200 mmHg, showing successive high amplitude peaks. HPP had a deleterious effects on tissue structure with tubular necrosis, and induced an increase in catalase (Cat) and a decrease in manganese superoxide dismutase (Mn SOD) and gluthatione peroxidase (GPx) activity. Copper zinc superoxide dismutase (Cu/Zn SOD) activity was not reduced except with CS+HPP. During CS, we observed an increase in GPx, Cu/Zn SOD and Cat activity, a decrease in Mn SOD activity and no histological alterations in the kidney. CS induces a slight oxidative stress which is not important enough to induce major tissue damage. HPP with UWCSS induces a stronger stress, which overpowers the antioxidant defences, inducing tissue damage. The reperfusion of HPP with UWCSS emphasises the stress initiated by CS. In addition an increase in damage occurred in the CS + HPP group.
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PMID:Impact of different combined preservation modalities on warm ischemic kidneys: effect on oxidative stress, hydrostatic perfusion characteristics and tissue damage. 1208 21

Chemical preconditioning using the mitochondrial toxin, 3-nitropropionic acid (3-NP) has been reported to induce neuroprotection against subsequent global ischemia. To investigate the underlying mechanisms, Mongolian gerbils were pretreated with either vehicle or 3-NP at the dose of 3 or 10 mg/kg, intraperitoneal, 3 days prior to a 5-min bilateral carotid artery occlusion followed by either 48 h or 7 days of blood recirculation. Neuronal damage was assessed by a cresyl violet/fuchsin acid staining. Induction of heat shock protein 72 (HSP72) and manganese superoxide dismutase (MnSOD) expression was evaluated by Western blotting. Astroglial and microglial activation was detected by immunohistochemistry (glial fibrillary acid protein) and by histochemistry (isolectin B4 staining), respectively. Present data show that the hippocampal neuronal damage induced by ischemia were of similar extent between the vehicle- and 3-NP-treated gerbils, whatever the dose tested, indicating that 3-NP did not induce tolerance to transient forebrain ischemia under our experimental conditions. The lack of difference in the post-ischemic level of HSP72 and MnSOD protein expression and in the intensity of astroglial and microglial activation represents further indirect indications of the absence of 3-NP preconditioning effect. In conclusion, although chemical preconditioning with 3-NP is a well-established phenomenon at least in vitro and in models of focal ischemia, the relevance of 3-NP as a preconditioning molecule towards global brain ischemia remains an open question.
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PMID:Chemical preconditioning with 3-nitropropionic acid: lack of induction of neuronal tolerance in gerbil hippocampus subjected to transient forebrain ischemia. 1212 10

Brief periods of non-lethal ischemia and reperfusion render the myocardium more resistant to subsequent ischemia. This adaption occurs in a biphasic pattern: the first being active immediately and lasting for 2-3 hrs (early preconditioning), the second starting at 24 hrs until 72 hrs after the initial ischemia (delayed preconditioning) and requiring genomic activation with de novo protein synthesis. Early preconditioning is more potent than delayed preconditioning in reducing infarct size; delayed preconditioning also attenuates myocardial stunning. Early preconditioning depends on the ischemia-induced release of adenosine and opioids and, to a lesser degree, also bradykinin and prostaglandins. These molecules activate G-protein coupled receptors, initiate the activation of KATP channels and generation of oxygen radicals, and stimulate a series of protein kinases with essential roles for protein kinase C, tyrosine kinases and members of the MAP kinase family. Delayed preconditioning is triggered by a similar sequence of events, but in addition essentially depends on eNOS-derived NO. Both early and pharmacological preconditioning can be pharmacologically mimicked by exogenous adenosine, opioids, NO and activators of protein kinase C. Newly synthetized proteins associated with delayed preconditioning comprise iNOS, COX-2, manganese superoxide dismutase and possibly heat shock proteins. The final mechanism of protection by preconditioning is yet unknown; energy metabolism, KATP channels, the sodium-proton exchanger, stabilisation of the cytoskeleton and volume regulation will be discussed. For ethical reasons, evidence for ischemic preconditioning in humans is hard to provide. Clinical findings that parallel experimental ischemic preconditioning are reduced ST-segment elevation and pain during repetitive PTCA or exercise tests, a better prognosis of patients in whom myocardial infarction was preceded by angina, and reduced serum markers of myocardial necrosis after preconditioning protocols during cardiac surgery with cardiac arrest. The most promising approach to apply principles of ischemic preconditioning therapeutically appears to be the pharmacological recruitment of delayed protection, as recently demonstrated with intravenous nitroglycerine in patients undergoing PTCA 24 hrs later.
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PMID:Ischemic preconditioning. Experimental facts and clinical perspective. 1247 80

The CXCR3 chemokine receptor, a member of the CXCR family, has been linked to a pathological role in autoimmune disease, inflammatory disease, allograft rejection, and ischemia. In the kidney, expression of the CXCR3 receptor and its ligands is up-regulated in states of glomerulonephritis and in allograft rejection, but little is known about the expression and functional role the CXCR3 receptor might play. Here, we study the function of the CXCR3 chemokine receptor in an immortalized human proximal tubular cell line (IHKE-1). Stimulation of the CXCR3 receptor by its selective agonist monokine induced by IFN-gamma leads via a Ca(2+)-dependent mechanism to an up-regulation of early growth response gene (EGR)-1. Overexpression of EGR-1 induces down-regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase and stimulates the generation of reactive oxygen species (ROS) via the NADH/NADPH-oxidase system. EGR-1 overexpression or treatment with monokine induced by IFN-gamma resulted in a ROS-dependent inhibition of basolateral Na(+)/K(+)-ATPase activity, compromising sodium transport in these cells. Thus, activation of the CXCR3 receptor in proximal tubular cells might disturb natriuresis during inflammatory and ischemic kidney disease via EGR-1-mediated imbalance of ROS.
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PMID:Up-regulation of early growth response gene-1 via the CXCR3 receptor induces reactive oxygen species and inhibits Na+/K+-ATPase activity in an immortalized human proximal tubule cell line. 1251 59

Endogenous tyrosine nitration and inactivation of manganese superoxide dismutase (MnSOD) has previously been shown to occur in both human and rat chronic renal allograft rejection. To elucidate the time course of MnSOD inactivation and mitochondrial dysfunction at earlier times during renal transplantation, we developed a rodent model of renal ischemia/reperfusion (I/R). Renal function was significantly impaired at 16 h reperfusion following 30 min of warm ischemia. Tyrosine nitration of specific mitochondrial proteins, MnSOD and cytochrome c, occurred at the earliest time point examined, an event that preceded significant renal injury. Interestingly, a small percentage of both mitochondrial proteins were also located in the cytosol. This leakage and decreased adenosine 5(')-triphosphate levels indicate loss of mitochondrial membrane integrity during renal I/R. Inactivation of MnSOD occurred rapidly in this model of renal I/R, suggesting that loss of MnSOD activity leads to further renal injury and nitration of other mitochondrial targets.
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PMID:Mitochondrial targets of oxidative stress during renal ischemia/reperfusion. 1264 64

Hepatic resection with concomitant periods of ischemia and reperfusion (I/R) is required to perform reduced size liver transplantation such as split liver or liver donor transplantation. Although great progress has been made using these types of surgeries, there remains substantial risk to both donors and recipients, with a significant number of patients developing liver injury and failure. The objective of this study was to assess the roles of superoxide (O(2)(-)) and tumor necrosis factor-alpha (TNF-alpha) in the pathophysiology of a mouse model of reduced size liver combined with ischemia and reperfusion (RSL+I/R). We found that all male mice subjected to RSL+I/R died within 3-5 days following surgery. Mortality was always preceded by dramatic increases in liver injury and TNF-alpha expression in the absence of neutrophil infiltration. Using a long-lived, polycationic form of human manganese superoxide dismutase (pcMnSOD), NADPH oxidase-deficient mice (gp91(-/-)) or a monoclonal antibody directed against mouse TNF-alpha, we demonstrated that hepatocellular injury (and mortality) were significantly attenuated. In addition, we found that pcMnSOD administration or NADPH deficiency reduced expression of TNF-alpha. Taken together, our data suggest that NADPH oxidase-derived O(2)(-) plays an important role in the pathophysiology of RSL+I/R-induced liver injury via its ability to enhance expression of TNF-alpha. We propose that therapies directed toward scavenging of O(2)(-), inhibiting NADPH oxidase, and/or immuno-neutralizing TNF-alpha may prove useful in limiting the liver injury induced by surgical procedures that require resection and I/R such as split liver or living donor liver transplantation.
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PMID:Role of NADPH oxidase-derived superoxide in reduced size liver ischemia and reperfusion injury. 1487 73

Endurance exercise provides cardioprotection against ischemia-reperfusion-induced myocardial stunning and infarction. A recent study demonstrates that an exercise-induced increase in myocardial manganese superoxide dismutase (MnSOD) activity is essential to protect the heart against infarction. It is unknown if an elevation in cardiac MnSOD is also a prerequisite to achieve exercise-induced protection against myocardial stunning. Therefore, this study determined if an exercise-induced increase in myocardial MnSOD activity is a requirement to achieve protection against myocardial stunning. Adult male rats remained sedentary or performed successive bouts of endurance exercise. Hearts were exposed to 25 min of global ischemia followed by reperfusion in an isolated working heart preparation. Postischemic recovery of cardiac external work during reperfusion was significantly higher (84 +/- 3 vs. 67 +/- 4%) in exercised animals compared with sedentary controls. Furthermore, prevention of exercise-induced expression of myocardial MnSOD via antisense oligonucleotides did not retard this exercise-induced protection against myocardial stunning. These data demonstrate that exercise-induced increases in cardiac MnSOD activity are not essential to achieve exercise-mediated protection against myocardial stunning. Therefore, we conclude that different mediators are responsible for exercise-induced cardioprotection against myocardial stunning and infarction.
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PMID:Elevated MnSOD is not required for exercise-induced cardioprotection against myocardial stunning. 1503 Nov 26

Uncoupling protein 2 (UCP2) is suggested to be a regulator of reactive oxygen species production in mitochondria. We performed a detailed study of brain injury, including regional and cellular distribution of UCP2 mRNA, as well as measures of oxidative stress markers following permanent middle cerebral artery occlusion in UCP2 knockout (KO) and wild-type (WT) mice. Three days post ischemia, there was a massive induction of UCP2 mRNA confined to microglia in the peri-infarct area of WT mice. KO mice were less sensitive to ischemia as assessed by reduced brain infarct size, decreased densities of deoxyuridine triphosphate nick end-labelling (TUNEL)-labelled cells in the peri-infact area and lower levels of lipid peroxidation compared with WT mice. This resistance may be related to the substantial increase of basal manganese superoxide dismutase levels in neurons of KO mice. Importantly, we found a specific decrease of mitochondrial glutathione (GSH) levels in UCP2 expressing microglia of WT, but not in KO mice after ischemia. This specific association between UCP2 and mitochondrial GSH levels regulation was further confirmed using lipopolysaccharide models of peripheral inflammation, and in purified peritoneal macrophages. Moreover, our data imply that UCP2 is not directly involved in the regulation of ROS production but acts by regulating mitochondrial GSH levels in microglia.
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PMID:Resistance to cerebral ischemic injury in UCP2 knockout mice: evidence for a role of UCP2 as a regulator of mitochondrial glutathione levels. 1514 21

Exercise provides protection against ischemia-reperfusion (I-R)-induced arrhythmias, myocardial stunning, and infarction. An exercise-induced increase in myocardial manganese superoxide dismutase (MnSOD) activity has been reported to be vital for protection against infarction. However, whether MnSOD is essential for exercise-induced protection against ventricular arrhythmias is unknown. We determined the effects of preventing the exercise-induced increase in MnSOD activity on arrhythmias during I-R resulting in myocardial stunning. Male rats remained sedentary or were subjected to successive bouts of endurance exercise. During in vivo myocardial I-R, the incidence of arrhythmias was significantly lower in the exercise-trained rats than in the sedentary rats as evidenced by the arrhythmia. When exercised rats were pretreated with antisense oligonucleotides directed against MnSOD, protection from arrhythmias was attenuated. Moreover, I-R resulted in significant increases in nitro-tyrosine (NT) in the sedentary group. Exercise abolished this I-R-induced NT formation but this protection was unchanged by antisense treatment. Protein carbonyls were increased by I-R, but neither exercise nor antisense treatment impacted carbonyl formation. These data demonstrate that an exercise-induced increase in MnSOD activity is important for protection against arrhythmias. The mechanism by which MnSOD provides protection does not appear to be linked to protein nitrosylation or oxidation.
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PMID:MnSOD antisense treatment and exercise-induced protection against arrhythmias. 1545 75


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