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

Efforts to minimize the deleterious effects of intraoperative myocardial ischemia-reperfusion (I/R) injury have been primarily directed at optimizing cardioplegic solutions and altering reperfusion conditions. Classically, myocardial I/R has been associated with cardiac mechanical dysfunction ("stunning"). Recently, we reported an alpha 1-adrenergic receptor-mediated mechanism of paradoxical myocardial protection against I/R insult induced by a prior episode of transient ischemia, a phenomenon known as "ischemic preconditioning." Myocardial stunning resulting from transient ischemia has previously been associated with ischemic preconditioning, prompting intuitively negative bias against the clinical application of this phenomenon. The purpose of this study was to determine whether transient ischemia of insufficient duration to cause prolonged mechanical dysfunction (stunning) can induce favorable cardiac preconditioning. Isolated-perfused rat hearts were allowed to equilibrate for 8 minutes and were then subjected to either 2 minutes of global, normothermic transient ischemia or 2 minutes of 50 mumol/L phenylephrine infusion. A stabilization period of perfusion lasting 10 minutes after the termination of transient ischemia or phenylephrine infusion was followed by a standard I/R challenge (20 minutes of global, normothermic ischemia; 40 minutes of reperfusion). Ventricular function (measured as developed pressure in millimeters of mercury) recovered rapidly after transient ischemia such that no impairment was present before the subsequent standard I/R challenge. Phenylephrine treatment was associated with no residual inotropy before I/R challenge. Control hearts were subjected only to the standard I/R challenge after an initial 20-minute equilibration period. After reperfusion control hearts exhibited 54.4% recovery of initial left ventricular developed pressure. Transient ischemia- and phenylephrine-preconditioned hearts recovered 84.4% (p < 0.01) and 82.4% (p < 0.01), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiac preconditioning does not require myocardial stunning. 843 Oct 49

1. We investigated alterations in dopamine D1 receptors in the striatum and hippocampus after transient cerebral ischemia in gerbils using [3H]SCH 23390 autoradiography. 2. We also examined the effect of vinconate against the alterations in dopamine D1 receptors after transient ischemia. 3. Transient ischemia was induced for 10 min, and vinconate (100 and 300 mg/kg) was given intraperitoneally 10 min before ischemia. 4. [3H]SCH 23390 binding showed no significant alterations in the striatum and hippocampus 5 hr after ischemia, whereas severe reduction in these areas was found after 7 days of recirculation. 5. Vinconate showed no significant alterations in [3H]SCH 23390 binding in the striatum and hippocampus except for a decrease in the hippocampal CA3 sector and dentate gyrus 5 hr after ischemia. By contrast, vinconate prevented a significant reduction in [3H]SCH 23390 binding in the striatum, hippocampal CA3 sector, hilus, and dentate gyrus 7 days after ischemia. 6. Vinconate inhibited lipid peroxidation in rat brain homogenates in a concentration-related manner. 7. These results indicate that free radicals generated from abnormal dopamine metabolism may play a key role in the development of ischemic brain damage. Furthermore, they suggest that vinconate prevents ischemic brain damage by inhibiting lipid peroxidation.
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PMID:Neuroprotective effect of vinconate against postischemic alterations in binding of [3H]SCH 23390 in the gerbil brain. 848 99

We previously reported that adenosine A1 receptor activation protects against the cardiodepressant effects of hydrogen peroxide in isolated rat hearts. The present study examined whether a transient ischemic period of 5 min duration, which preconditions the heart against ischemic and reperfusion-induced dysfunction, can bestow protection against 30-min exposure to hydrogen peroxide in isolated rat hearts. Transient ischemia on its own failed to alter the cardiac response to hydrogen peroxide. However, when transient ischemia was carried out in the presence of the nucleoside transport inhibitor S-(4-Nitrobenzyl)-6-thioguanosine and the adenosine deaminase inhibitor erythro-9-(2-Hydroxy-3-nonyl)adenine, a significant attenuation of the hydrogen peroxide-induced loss in contractility was evident and this was associated with significant preservation of tissue glycogen content. The protective effect of the transient ischemia/drug combination on both functional changes and glycogen levels was abolished by the adenosine A1 receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine as well as by glibenclamide, a blocker of the ATP-sensitive potassium channel (KATP). To further assess the role of glycogen in the protection against hydrogen peroxide, we compared the effects of the adenosine A1 agonist N6-cyclopentyl adenosine (CPA) and insulin. While both treatments protected against hydrogen peroxide the effect of insulin was superior to any other treatment. Moreover, while all protective modalities preserved glycogen stores after hydrogen peroxide treatment, the protection afforded by insulin was also associated with significantly elevated glycogen levels prior to hydrogen peroxide administration. No protection by either CPA or insulin was evident in the absence of exogenous glucose. Taken together, our results demonstrate that a brief period of ischemia with concomitant administration of agents which increase interstitial adenosine levels protects against hydrogen peroxide toxicity. The effect is mediated by activation of adenosine A1 receptors and is linked to KATP stimulation. Moreover, our results are strongly suggestive of an important role of glycogen preservation in bestowing protective effects against hydrogen peroxide cardiotoxicity.
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PMID:Transient ischemia in the presence of an adenosine deaminase plus a nucleoside transport inhibitor confers protection against contractile depression produced by hydrogen peroxide. Possible role of glycogen. 876 52

Following selective neuronal death, numerous presynaptic terminals maintain their structural integrity in the brain region. The role that these remaining presynaptic terminals play in the brain region showing selective neuronal death is not known. In the present study, we investigated the possibility that brief transient ischemia induces an excessive release of glutamate from the remaining presynaptic terminals, which then spreads by diffusion. The glutamate could act as an excitotoxin and be a pathogenic factor in the local injured brain region. Transient ischemia of 3.5 min duration was used in the gerbil as a pretreatment to obtain hippocampal CA1 in which most of postsynaptic neurons were eliminated but numerous presynaptic terminals remained normal. At 10-14 days after the pretreatment, brain microdialysis experiments were performed in vivo in the CA1 to measure the levels of extracellular glutamate induced by 5 min ischemia. Prior to 5 min ischemia the basal concentration of glutamate in the CA1 was the same as that observed in gerbils that had been subjected to sham pretreatment. During 5 min ischemia, no significant increase in glutamate was induced in the CA1 which showed selective neuronal death. However, a massive increase in glutamate was induced in the CA1 of the sham-pretreated gerbils. These results suggest that the remaining presynaptic terminals are unlikely to play a pathogenic role in the CA1 after selective neuronal death has occurred.
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PMID:The role of remaining presynaptic terminals in the hippocampal CA1 after selective neuronal death: ischemia-induced glutamate efflux. 877 44

The effect of retrograde perfusion of the cerebral vein (RPCV) with antioxidant LY231617 on neuronal injury after transient ischemia in rat brain was examined. Transient ischemia was caused by left middle cerebral artery (MCA) occlusion and reperfusion. Rats were assigned to three groups: Group A (n = 6), MCA occlusion only; Group B (n = 8), RPCV with saline (flow rate 4.95 ml/hr) into the left inferior cerebral vein; and Group C (n = 6), RPCV with LY231617 (20 mg/kg/hr, flow rate 4.95 ml/hr). RPCV in Groups B and C was performed simultaneously with occlusion. Both occlusion and RPCV were performed for 30 minutes in awake animals. Seven days later, all rats were investigated for rotational behavior elicited by apomorphine (1.0 mg/kg), and then immunohistochemical analysis of brain specimens was carried out using calcineurin as a neuronal marker in the striatum to detect the ischemic damaged area. The number of turns to the left (lesioned side) in both Groups B (42 +/- 12) and C (46 +/- 14) was significantly lower (p < 0.01) than in Group A (222 +/- 45), but there was no significant difference between Groups B and C. The percentage ischemic damaged area in both Groups B (17.9 +/- 6.2%) and C (1.6 +/- 1.0%) was significantly less (p < 0.01) in Group A (51.1 +/- 2.1%). RPCV with and without LY231617 during occlusion was effective for attenuating reperfusion injury.
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PMID:Effectiveness of retrograde perfusion of the cerebral vein for attenuating neuronal injury after transient ischemia following reperfusion in the rat brain. 909 24

Transient ischemia on Holter monitoring is a major determinant of outcome in unstable angina. In this study we investigated whether analysis of heart rate variability (HRV) may further improve the prognostic yield of Holter monitoring in this clinical setting. We performed 24-hour Holter monitoring in 75 patients with unstable angina (59 men, aged 62 +/- 9 years) within 12 hours of hospital admission. Number and duration of myocardial ischemic episodes, and both time domain and frequency domain HRV measures were obtained from Holter recordings. In-hospital major cardiac events (death or myocardial infarction) occurred in 7 patients (9%). Episodes of ST-segment depression on Holter monitoring were found in 6 of 7 patients (86%) with and in 26 of 68 patients (38%) without events (p <0.05). There were no differences between patients with or without events in both time domain (standard deviation [SD] of all normal RR intervals in the entire 24-hour electrocardiographic recording (SDNN), SD of the mean RR intervals for all 5-minute segments (SDANN-i), mean of SD of all RR intervals for all 5-minute segments (SDNN-i), percentage of differences between adjacent RR intervals >50 ms (pNN50), and square root of the mean squared differences of successive RR intervals) (RMSSD), and frequency domain (ultra low, very low, low, and high frequency) HRV indexes. However, the low-frequency/high-frequency (LF/HF) ratio was significantly higher in patients with cardiac events (2.12 +/- 1.4 vs 1.48 +/- 0.5, p = 0.01). Moreover, when considering only the 32 patients with myocardial ischemic episodes on Holter monitoring, the LF/HF ratio was again higher in the 6 patients with than the 26 patients without major cardiac events (2.45 +/- 1.5 vs 1.31 +/- 0.3, p <0.01). Multivariate logistic regression, including clinical and angiographic variables, showed that transient ischemia on Holter monitoring was the only independent determinant of outcome (odds ratio = 12.2, p = 0.03), with the LF/HF ratio being only slightly over statistical significance (odds ratio for 0.1 increments = 2.8, p = 0.08). Our data confirm that transient ischemia on Holter monitoring is a powerful predictor of cardiac events in unstable angina and indicates that an imbalance in cardiac autonomic tone toward a prevalence of sympathetic activity increases the risk of events in this group of patients.
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PMID:Usefulness of the addition of heart rate variability to Holter monitoring in predicting in-hospital cardiac events in patients with unstable angina pectoris. 926 16

Activation of the N-methyl-D-aspartate (NMDA) receptor has been implicated in the events leading to ischemia-induced neuronal cell death. Recent studies have indicated that the properties of the NMDA receptor channel may be regulated by tyrosine phosphorylation. We have therefore examined the effects of transient cerebral ischemia on the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B in different regions of the rat brain. Transient (15 min) global ischemia was produced by the four-vessel occlusion procedure. The tyrosine phosphorylation of NR2A and NR2B subunits was examined by immunoprecipitation with anti-tyrosine phosphate antibodies followed by immunoblotting with antibodies specific for NR2A or NR2B, and by immunoprecipitation with subunit-specific antibodies followed by immunoblotting with anti-phosphotyrosine antibodies. Transient ischemia followed by reperfusion induced large (23-29-fold relative to sham-operated controls), rapid (within 15 min of reperfusion), and sustained (for at least 24 h) increases in the tyrosine phosphorylation of NR2A and smaller increases in that of NR2B in the hippocampus. Ischemia-induced tyrosine phosphorylation of NR2 subunits in the hippocampus was higher than that of cortical and striatal NR2 subunits. The enhanced tyrosine phosphorylation of NR2A or NR2B may contribute to alterations in NMDA receptor function or in signaling pathways in the postischemic brain and may be related to pathogenic events leading to neuronal death.
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PMID:Transient ischemia differentially increases tyrosine phosphorylation of NMDA receptor subunits 2A and 2B. 928 28

We examined the functionality of hippocampal CA1 neurons at early times after transient global ischemia, by electrophysiologic recordings in brain slices. Transient ischemia was conducted on rats using the method of 15-minute four-vessel occlusion, and brain slices were obtained from these animals at different times after ischemia. Within 24 hours after insult, CA1 neurons showed no substantial damage as identified by morphologic means, but exhibited dramatic decreases in synaptic activities by 12 hours after insult, which became further decreased at more extended times after recovery. Blocking gamma-aminobutyric acid A (GABAA) receptors with bicuculline produced a reversible augmentation of the diminished synaptic responses in slices prepared from 12-hour postinsult animals, but failed to do so in slices obtained from rats 24 hours after insult. Recorded in whole-cell mode, the minimum depolarizing current required to elicit an action potential was about twofold larger in the ischemic CA1 neurons than in sham controls, suggesting that an elevated spiking threshold exists in these neurons. We suggest that decreases in electrophysiologic activities precede the morphologic deterioration in postischemic CA1 neurons. The early decrease in CA1 synaptic activities may be associated with an imbalance between glutamate-mediated synaptic excitation and GABAA-mediated synaptic inhibition, whereas substantial impairments in synaptic transmission likely take place after prolonged post-ischemic recovery.
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PMID:Transient ischemia induces an early decrease of synaptic transmission in CA1 neurons of rat hippocampus: electrophysiologic study in brain slices. 930 9

The goal of this study was to determine whether aurintricarboxylic acid (ATA), an endonuclease inhibitor known to inhibit apoptosis, could ameliorate cell damage in a gerbil model of transient ischemia. Transient ischemia was induced in gerbils by bilateral carotid artery occlusion for a period of 5 minutes. Four micrograms of ATA was administered intraventricularly 1 hour before ischemia, and the brains were assessed histologically 1 week later to quantitate cell loss in the vulnerable CA-1 subsector of the hippocampus. In a separate set of experiments, 4 microg of ATA was administered intraventricularly 1 hour before ischemia and the brains were assessed for evidence of DNA fragmentation by the TUNEL method. There was only a 16% cell loss compared with nonischemic controls in animals pretreated with ATA that was significantly less (p < 0.05) than the 48% cell loss in animals pretreated with saline alone. TUNEL-positive cells were first evident at 3 days and were still present at 7 days subsequent to ischemia. Maximal staining occurred at 4 days. Pretreatment with ATA virtually eliminated TUNEL staining at 4 days. These results support the hypothesis that the delayed cell death secondary to transient ischemia is, in part, apoptotic. Furthermore, ATA afforded significant neuronal protection and prevented DNA fragmentation.
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PMID:Pretreatment with intraventricular aurintricarboxylic acid decreases infarct size by inhibiting apoptosis following transient global ischemia in gerbils. 958 61

Using in situ hybridization, Northern blot analysis, Western blot analysis, and immunocytochemistry, mRNA and protein expression of the novel DNA damage-inducible gene GADD45 was examined in the rat brain at 0.5, 2, 4, 8, 16, 24, 48, and 72 hours after 15 minutes of transient global ischemia. Transient ischemia produced by the four-vessel occlusion method resulted in DNA double-strand breaks and delayed neuronal cell death in vulnerable neurons of the hippocampal CA1 sector, the hilus, dorsal caudate-putamen, and thalamus, as shown by in situ DNA nick end-labeling and histologic staining. GADD45 mRNA was transiently increased in less-vulnerable regions such as the parietal cortex (up to 8 hours after ischemia) and dentate granule cells (up to 24 hours after ischemia) but was persistently increased in vulnerable neurons such as CA1 pyramidal neurons (up to 48 hours). GADD45 immunoreactivity was increased in both vulnerable and less-vulnerable regions at earlier reperfusion periods (4 to 16 hours), but thereafter immunoreactivity was decreased below control levels in most vulnerable regions before delayed cell death and DNA double-strand breaks. At 72 hours after transient ischemia, a moderate increase in GADD45 immunoreactivity was still detectable in some CA3 neurons and in a few surviving neurons in the CA1 region. Double staining performed at 16 to 72 hours after ischemia revealed that GADD45 immunoreactivity was persistently increased in neurons that did not develop DNA damage. Because GADD45 protein may participate in the DNA excision repair process and because it has been shown that this protein is also overexpressed in neurons that survive focal ischemia and kainate-induced epileptic seizures, the results reported here support the hypothesis that GADD45 could have a protective role in neuronal injury.
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PMID:Transient global ischemia triggers expression of the DNA damage-inducible gene GADD45 in the rat brain. 962 89


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