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

The transgenic mice overexpressing heat shock protein 72 (HSP72) or antioxidants have been reported to be more resistant to myocardial ischemia/reperfusion injury. However, it remains unknown whether whole body heat stress (HS) which may induce HSP72 or endogenous antioxidants affords similar protection in the mouse heart. Adult male mice were treated with either HS (42 degrees C for 15 min) or anesthesia only (SC) against a group of non-stressed controls (NC). At 6 or 24 h later, the hearts were excised and perfused at a constant pressure of 55 mmHg in Langendorff mode. Following 30 min equilibration, hearts were subjected to 20 min of global ischemia and 30 min reperfusion (37 degrees C). Ventricular force was measured by a force-displacement transducer attached to the apex. Leakage of intracellular enzymes (CK, LDH) was measured in coronary efflux. Infarct size was determined by tetrazolium staining. The results showed that no significant differences between HS, SC, and NC groups in ventricular contractile function, CK and LDH release, or infarct size were observed at either time window. HS enhanced the expression of HSP72 in mouse hearts by two- to three-fold, whereas antioxidant enzyme activities (catalase and MnSOD) did not change significantly. We conclude that HS does not precondition the isolated perfused mice hearts against ischemia/reperfusion injury, despite induction of HSP72.
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PMID:Whole body heat shock fails to protect mouse heart against ischemia/reperfusion injury: role of 72 kDa heat shock protein and antioxidant enzymes. 992 59

While the role of heat shock protein 72 (HSP72) in protection of the ischemic heart has been studied extensively, the expression and localization of HSP72 in the ischemic and reperfused heart remains poorly understood. This study examined the expression and distribution of HSP72 after various periods of ischemia and reperfusion in the non-stress-pretreated rat heart. The distribution of HSP72 in the myocardium was examined immunohistochemically using a specific monoclonal antibody for detection of this protein. The levels of HSP72 mRNA in the myocardium were estimated by the reverse transcriptase polymerase chain reaction (RT-PCR) method. Rats were subjected to either permanent occlusion of the left coronary artery or 30 min of occlusion followed by reperfusion, and they were sacrificed 30 min, 4 h, 24 h and 7 days thereafter. Both permanent ischemia and reperfusion induced expression of HSP72 mRNA in the ischemic myocardium from 30 min to 24 h after the onset of ischemia/reperfusion. The maximum mRNA level, which appeared at 4 h, was much higher in the reperfusion group than in the permanent ischemia group. Myocytes exhibited definite immunoreactivity of HSP72 at 4 h and 24 h in both groups, and microvessels exhibited strong immunoreactivity at 4 h in the reperfusion group. This study revealed the time course of expression and distribution of HSP72 in the ischemic and reperfused hearts in vivo.
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PMID:Time course of expression and localization of heat shock protein 72 in the ischemic and reperfused rat heart. 1047 76

In the present study, we investigated whether neurons adjacent to an ischemic lesion acquire tolerance against subsequent ischemia or not. We initially used unilateral hemispheric ischemia for 3 min in gerbils to produce an ischemic lesion confined to the unilateral CA1 sector, and the presence of tolerance was examined in the adjacent CA3 sector through transient global ischemia by occlusion of both common carotid arteries. Attenuation of neuronal damage was clearly observed in neurons in the CA3 sector adjacent to the ischemic lesion in the CA1 sector. The phenomenon lasted for up to two weeks after the initial hemispheric ischemia, but was no longer present two months later. Reactive astrocytes as identified by the presence of glial fibrillary acidic protein were visible in the CA3 hippocampus four days and two weeks after hemispheric ischemia, but they were scarce two months later. Expression of heat shock protein 72 in the CA3 neurons was observed four days after hemispheric ischemia, but the reaction returned to the control level two weeks later. In conclusion, the present study showed that tolerance in the neurons adjacent to an ischemic lesion could be sustained at least for two weeks, and raised the possibility that reactive astrocytes might contribute to the extended tolerance in neurons.
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PMID:Extended neuronal protection induced after sublethal ischemia adjacent to the area with delayed neuronal death. 1068 19

Acute administration of glucocortiocoids reduces inflammation. Increasing knowledge of the mechanisms of action indicate that pretreatment with glucocorticoids could have organ-protective effects. We investigated whether pretreatment with methylprednisolone (MP) protected the heart against ischemia-reperfusion dysfunction, and we hypothetized that this protection might be due to induction of the cardioprotective heat shock protein 72 (HSP72). Rats were given vehicle or MP-40 mg/kg im as a double injection starting either 24 or 120 h (5 days) before their hearts were excised for Langendorff perfusion (n = 6-11 hearts in each group). MP improved left ventricular function and coronary flow during reperfusion after 30 min of global ischemia and reduced infarct size. Cardiac HSP72 gradually increased in a 24-h time course after MP treatment, and the increase was sustained 5 days afterward (immunoblotting). HSP72 mRNA was either reduced or unchanged, indicating a posttranscriptional regulation. Pretreatment with hydrocortisone or dexamethasone (n = 7-8 hearts of each) similarily increased cardiac HSP72 24 h afterward. This paper demonstrates that glucocorticoids increase cardiac HSP72 and protect organ function against ischemia-reperfusion injury.
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PMID:Glucocorticoid pretreatment protects cardiac function and induces cardiac heat shock protein 72. 1092 84

Oxidative stress may precondition the heart. The present study investigated whether hyperoxia elicits a preconditioning-like response. Rats were kept in a hyperoxic (>95% O2) environment for 60 or 180 minutes. Hearts were Langendorff-perfused immediately or 24 hours after hyperoxia, and exposed to 25 minutes of global ischemia and 60 minutes of reperfusion. Whole blood was sampled after 60 and 180 minutes of hyperoxia for oxidative stress markers. Hearts were sampled immediately or 24 hours after hyperoxia for measurement of antioxidants, lipid peroxidation products, heat shock protein 72 and endothelial nitric oxide synthase. At the end of reperfusion after 1 h hyperoxia, infarct size was determined by tetrazolium staining. Hyperoxia increased serum levels of conjugated dienes, reduced serum antioxidative protection, reduced reperfusion arrhythmias in most groups, and improved myocardial function. Infarct size was reduced from 45% of myocardial tissue in controls to 22% in treated animals. The myocardial activity of antioxidant enzymes, content of heat shock protein 72, and endothelial nitric oxide synthase in myocardial tissue were not influenced. In conclusion, hyperoxia induces a low-graded systemic oxidative stress, improves postischemic cardiac function and reduces infarct size. The mediators of protection remain to be determined.
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PMID:Pretreating rats with hyperoxia attenuates ischemia-reperfusion injury of the heart. 1126 75

Oxidative stress is a prominent feature of the placenta in many complications of pregnancy, such as preeclampsia. The cause is primarily unknown, although ischemia-reperfusion injury is one possible mechanism. Our aim was to test this hypothesis by examining the oxidative status of human placental tissues during periods of hypoxia and reoxygenation in vitro. Rapid generation of reactive oxygen species was detected using the fluorogenic probe, 2',7'-dichlorofluorescein diacetate, when hypoxic tissues were reoxygenated. The principal sites were the villous endothelium, and to a lesser extent the syncytiotrophoblast and stromal cells. Increased concentrations of heat shock protein 72, nitrotyrosine residues, and 4-hydroxy-2-nonenal were also observed in the villous endothelial and underlying smooth muscle cells, and in the syncytiotrophoblast. Furthermore, preloading placental tissues with the reactive oxygen species scavengers desferrioxamine and alpha-phenyl-N-tert-butylnitrone reduced levels of oxidative stress after reoxygenation. These changes are consistent with an ischemia-reperfusion injury, and mirror those seen in preeclampsia. Consequently, in vitro hypoxia/reoxygenation may represent a suitable model system for investigating the generation of placental oxidative stress in preeclampsia and other complications of pregnancy.
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PMID:In vitro ischemia-reperfusion injury in term human placenta as a model for oxidative stress in pathological pregnancies. 1154 95

Disruption of cell contact sites during ischemia contributes to the loss of organ function in acute renal failure. Because prior heat stress protects cell contact sites in ATP-depleted renal epithelial cells in vitro, we hypothesized that heat shock protein 72 (HSP72), the major inducible cytoprotectant in mammalian cells, interacts with protein kinases that regulate cell-cell and cell-matrix interactions. ATP depletion increased the content of Tyr(416) Src, the activated form of this kinase. c-Src activation was associated with an increase in the tyrosine phosphorylation state of beta-catenin, paxillin, and vinculin, three c-Src substrate proteins that localize to and regulate cell contact sites. Prior heat stress inhibited c-Src activation and decreased the degree of tyrosine phosphorylation of all three Src substrates during ATP depletion and/or early recovery. HSP72 coimmunoprecipitated with c-Src only in cells subjected to heat stress. ATP depletion markedly increased the interaction between HSP72 and c-Src, supporting the hypothesis that HSP72 regulates Src kinase activity. These results suggest that alterations in the tyrosine phosphorylation state of proteins located at the cell-cell and cell-matrix interface mediate, at least in part, the functional state of these structures during ATP depletion and may be modulated by interactions between HSP72 and c-Src.
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PMID:c-Src and HSP72 interact in ATP-depleted renal epithelial cells. 1160 Apr 31

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

Heat shock preconditioning (HSPC) is a promising strategy for providing ischemic tolerance. The objective of this study is to investigate the effectiveness of HSPC in preventing oxidative damage of cellular proteins and DNA during ischemia-reperfusion of the liver. Male Wistar rats were divided into a heat shock group (group HS) and control (group C). Forty-eight hours prior to ischemia, rats in group HS received HSPC at 42 degrees C for 15 min. All rats received hepatic warm ischemia for 30min and subsequent reperfusion. The formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE) modified proteins in liver tissue, survival rate of the animals, and changes in biochemical and histological parameters were compared between groups. Heat shock protein 72 was produced only in group HS. The 7-day survival of rats was significantly better in group HS (10/10) than in group C (5/10) (p < 0.01). The serum release of alanine aminotransferase (n = 10, p < 0.01) and the concentration of adenosine triphosphate in liver tissue (n = 10, p < 0.01) 40min after reperfusion was significantly better in group HS than in group C. The formation of 8-OHdG in liver tissue measured by high-performance liquid chromatography was suppressed in group HS (p < 0.01). The production of HNE-modified proteins as determined by Western-blot analysis was also decreased in group HS. These results were also confirmed by immunohistochemical analysis. As determined by levels of 8-OHdG and HNE-modified proteins produced during ischemia-reperfusion of the liver, HSPC reduced the oxidative injury of cellular proteins and DNA in the liver tissue.
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PMID:Heat shock preconditioning reduces the formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal modified proteins in ischemia-reperfused liver of rats. 1199 85

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


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