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)

The purpose of this study was to investigate the effect of the oxidants hypochlorous acid (HOCl) and hydrogen peroxide (H2O2) on the vulnerability of the myocardium to reperfusion-induced arrhythmias following global ischemia. After a 15 min equilibration period with or without experimental intervention, isolated perfused rat hearts in the Langendorff mode were made globally ischemic for 5 min by cross-clamping the aortic line. No dysrhythmias were evoked upon reperfusion at the 5 min global ischemia time period. HOCl or H2O2 were added to the perfusate 5 min into the equilibration period with a total exposure of 10 min. Global ischemia was then induced for 5 min followed by 10 min of reperfusion. A dose-response curve for HOCl (50-200 microM) indicated the development of idioventricular rhythms, in a concentration-dependent way. Furthermore, coronary flow of the hearts exposed to 100 and 200 microM HOCl, at 5 min post-reperfusion, was decreased; methionine (10 microM to 1 mM), an accepted scavenger for HOCl, prevented the responses to 200 microM HOCl, in a concentration-dependent manner. All hearts exposed to 200 microM H2O2 developed ventricular dysrhythmias during the reperfusion period. Coronary flow increased after 5 min of exposure to 200 microM H2O2 and remained elevated during reperfusion. It is concluded that toxic oxygen derived products are capable of increasing the susceptibility of the myocardium to reperfusion induced arrhythmias, and that although the electrical responses to exposure to those two oxidants were similar, the effects on the vasculature were not the same.
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PMID:The effect of hypochlorous acid and hydrogen peroxide on coronary flow and arrhythmogenesis in myocardial ischemia and reperfusion. 839 7

To determine the exercise workload, ECG, and thallium-201 image parameters that are most closely associated with a poor prognosis from ischemic heart disease, the test results of 268 patients were reviewed. Only patients with unequivocal thallium-201 redistribution were selected. A multivariate analysis was performed to find the variables that were most strongly associated with the outcomes of coronary revascularization, myocardial infarction, and cardiac death during a follow-up period of 25 +/- 19 months. Patients who underwent early elective revascularization had poorer exercise tolerance and more thallium image abnormalities than those with no events. In the remaining patients myocardial infarction was most closely related to the extent and severity of thallium ischemia (p = 0.0086), whereas cardiac death was associated with abnormal thallium lung uptake (p = 0.0082) and an inability to exercise to 9.6 MET (p = 0.0144). Thus unlike myocardial infarction, cardiac death is best predicted by variables that reflect poor left ventricular function rather than those that indicate ischemia.
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PMID:Variables associated with a poor prognosis in patients with an ischemic thallium-201 exercise test. 842 25

A rat model of fatty liver transplantation has been developed to study primary nonfunction in fatty liver grafts. ACI rats were fed with a diet deficient in choline and methionine for 7, 14, 28, and 42 days. Fat content in the pretransplant livers was examined by gas chromatography and histology. The main constituent of the fatty droplets was determined to be triglyceride. The triglyceride concentration reached a maximum by day 14 and remained constant for an additional 28 days. Histology revealed an absence of necrosis in 14- and 28-day fatty livers but scattered hepatocytic necrosis and inflammation in 42-day fatty livers. After being given cold (UW stored, 4 degrees C) or warm (37 degrees C) ischemia, the fatty liver was orthotopically transplanted into normal ACI rats. The one-week survival of fatty liver grafts after 6, 12, 18, and 24 hr cold preservation was 5/5, 5/6, 3/8, 0/6 for 14-day fatty liver and 5/5, 4/6, 0/8, 0/6 for 42-day fatty livers. The survival of normal liver grafts was 5/5, 6/6, 5/9, 2/8, respectively. Increased survival rate was correlated with the absence of hepatocytic necrosis. The survival after 15 and 30 min warm ischemia prior to transplant was 5/5, 2/6 for normal liver grafts and 4/7, 0/6 for 28-day fatty liver graft, respectively. Fatty livers were less resistant to damage induced by cold or warm ischemia.
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PMID:A rat fatty liver transplant model. 847 45

Neuronal protein synthesis is severely depressed following stress such as heat-shock, hypoxia, and hypoglycemia. Following reversible cerebral ischemia, protein synthesis is transiently inhibited in ischemia-resistant areas, but persistently depressed in vulnerable brain regions. Eukaryotic initiation factor 2 (eIF-2) activity, that is, the formation of the ternary complex eIF-2.GTP.initiator 35S-Met-tRNA, a rate-limiting step in the initiation of cellular protein synthesis, was studied in the rat brain during and following 15 min of transient global cerebral ischemia. At 30 min and 1 hr of reperfusion, a general decrease of eIF-2 activity by approximately 50% was seen in the postmitochondrial supernatant (PMS). In the relatively resistant neocortex and CA3 region of the hippocampus, the eIF-2 activity returns to control levels at 6 hr of reperfusion, but remains depressed in the vulnerable striatum and the CA1 region. Similarly, the activity of the guanine nucleotide exchange factor (GEF), which catalyzes the exchange of GTP for GDP bound to eIF-2, a crucial step for the continued formation of the ternary complex, is transiently reduced in neocortex but persistently depressed in striatum. The postischemic decrease in eIF-2 activity is further attenuated by agarose-bound alkaline phosphatase, and mixing experiments revealed that a vanadate-sensitive phosphatase may be responsible for the depression. Addition of partially purified GEF to PMS from postischemic neocortex restored eIF-2 activity to control levels. We conclude that ischemia alters the balance between phosphorylation and dephosphorylation reactions, leading to an inhibition of GEF and a depression of ternary complex formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stress-induced inhibition of protein synthesis initiation: modulation of initiation factor 2 and guanine nucleotide exchange factor activities following transient cerebral ischemia in the rat. 847 77

The alteration of calcium homeostasis is of outstanding importance for the cytotoxic reactions that place after ischemia, for this reason calcium channel blockers have been used with the purpose to protect the lung during transplantation. This work analyses the effect of Diltiazem at two different doses (10 mg/l and 50 mg/l) on Wistar rat alveolar type II cells, incubated for 8 hours at 37 degrees C and at 4 degrees in an electrolytic solution. Total protein content and the rate of protein synthesis derived from 35S Methionine uptake were used to evaluate cells viability. The data showed that Diltiazem did not improve cellular viability after warm and cold metabolic ischemia either using 10 mg/l or 50 mg/l, while at 4 degrees C a significantly cytotoxic effect (p < 0.05) was observed. At this temperature toxicity was independent on the dose used.
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PMID:The influence of high and low doses of diltiazem on isolated alveolar type II cells during normothermic and hypothermic ischemia: cytoprotection or cytotoxicity? 859 20

Induction of stress proteins is thought to be important in the protection of cells from a variety of environmental insults including heat, hypoxia and ischemia. The aim of this study was to compare the mechanism of induction of heat shock protein 72 (HSP72) in primary cultures of murine cortical astrocytes by heat and combined oxygen-glucose deprivation (OGD), a model of in vitro ischemia. 35S-methionine labeling and immunoblotting showed increased HSP72 synthesis and accumulation lasting for up to 24 h following heat or OGD. Heat induced a markedly greater amount of HSP72 mRNA and protein than did OGD. We then sought evidence of heat shock transcription factor-1 (HSF-1) activation. An increase in apparent molecular weight of nuclear HSF-1 after heat or OGD was observed, consistent with increased phosphorylation. To seek an explanation of the difference between heat and OGD as inducers of HSP72 we examined the binding activity of HSP72 + 73 to other proteins. More cellular protein was found to co-immunoprecipitate with HSP72 + 73, and more HSP72 + 73 was found in the pellet fraction after heat shock compared to OGD. These results suggest that HSP72 induction is regulated in astrocytes at least in part at the level of HSF activation, by both heat and OGD. Reduced availability of free HSP72 + 73 in heated cells could be responsible for the greater magnitude of HSP72 induction after heat compared to OGD.
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PMID:Mechanism of heat shock protein 72 induction in primary cultured astrocytes after oxygen-glucose deprivation. 871 40

We investigated whether the known neuroprotective effects of two selective glutamate receptor antagonists, the NMDA antagonist MK-801 and the AMPA antagonist NBQX, are reflected in the regional cerebral protein synthesis rates (CPSR) in rats with middle cerebral artery occlusion (MCAO). Rats treated with either saline, MK-801 (5 mg/kg i.p.) or NBQX (30 mg/kg i.p. x 3) were subjected to permanent MCAO. Regional CPSR and volumes of gray matter structures displaying normal CPSR were measured in coronal cryosections of the brain by quantitative autoradiography following an i.v. bolus injection of 35S-labelled L-methionine 2 h after occlusion. MCAO completely inhibited protein synthesis in the lateral part of striatum and part of the adjacent frontoparietal cortex corresponding to the ischemic focus. Surrounding this, a metabolic penumbra with approximately 50% reductions in CPSR was present. Treatment with MK-801 significantly increased the volume of tissue with normal CPSR in the ischemic hemisphere compared to controls, whereas this was not seen with NBQX treatment. The results suggest that MK-801 and NBQX have different effects on peri-infarct protein synthesis after MCAO. Since both compounds reduce infarct size, it is questionable that acute inhibition of protein synthesis in focal ischemia is of significant importance to the final outcome of a stroke lesion.
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PMID:Differential effect of NMDA and AMPA receptor blockade on protein synthesis in the rat infarct borderzone. 874 Nov 37

The normal vascular wall contains resident leukocytes, notably tissue macrophages (histiocytes) and mast cells, that confer a rapid, eicosanoid-dependent vasoconstrictor response to agonists typical of leukocytes, such as the complement-derived anaphylatoxin C5a or the formylated peptide f-Met-Leu-Phe (isolated organ methodology). The eicosanoid-dependent vasomotor response is even more intense in pathologies that involve leukocyte infiltration of the blood vessel wall, such as atherosclerosis and serum sickness in the rabbit. The leukocyte compartment of the blood vessel is the likely source of vasoactive mediators (eicosanoids, radicals, cytokines) of physiopathological importance, with possible application in cardiac ischemia, lupus nephritis, vasculitides, and graft rejection. This line of investigation may be compared to the discovery and characterization of endothelium-dependent vasomotor responses. However, the problem is experimentally more demanding: histological correlations, experiments based on leukocyte depletion, reconstitution, and enrichment are useful approaches to document this form of circulatory control.
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PMID:Evidence for vascular tone regulation by resident or infiltrating leukocytes. 893 61

We have studied the beneficial effects of S-adenosyl-L-methionine (SAM) tosylate on blood-brain barrier (BBB) breakdown and neuronal survival after transient cerebral ischemia in gerbils. BBB breakdown experiments were performed in pentobarbital anesthetized gerbils subjected to 10 min of bilateral carotid artery occlusion and 6 h of reperfusion. For BBB breakdown measurements, SAM (120 mg/kg, i.p.) was administered to gerbils just after occlusion and thereafter every hour up to 5 h. Fluorometric measurements quantified the blood-brain permeability tracer, Evans blue (EB). SAM treatment significantly reduced the BBB breakdown as indicated by reduced levels of EB fluorescence. Neuronal count experiments were conducted in gerbils subjected to transient ischemia and 7 days of reperfusion. For neuronal count experiments SAM (15-120 mg/kg) was administered at 6 and 12 h after reperfusion, and twice each day thereafter for 7 days. SAM dose dependently protected the hippocampal CA1 neurons assessed by histopathological methods. SAM has a beneficial effect on the outcome of ischemic injury by reducing the BBB breakdown and neuronal death.
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PMID:Beneficial effects of S-adenosyl-L-methionine on blood-brain barrier breakdown and neuronal survival after transient cerebral ischemia in gerbils. 903 Jul 7

The primary objective of this study was to attempt to induce excessive intraglial acidosis during ischemia by subjecting rats to an initial insult which leads to post insult accumulation of glycogen, presumed to accumulate primarily in astrocytes. The initial insults were 15 min of transient forebrain ischemia, 30 min of hypoglycemic coma, and intraperitonial injection of methionine-sulphoximine (MSO). In the first two of these insults, glycogen content in neocortex increased to 6-7 mM kg(-1) after 6 h of recovery, and in MSO-treated animals even higher values were measured 24 h after administration ( 12 mM kg(-1)). In spite of this glycogen loading, the amount of lactate formed during a subsequent ischemic insult (of 5-30 min duration) did not exceed values usually obtained during complete ischemia in animals with normal glycogen contents (tissue lactate contents of 15 mM kg(-1)) This was because appreciable amounts of glycogen (3-7 mM kg(-1)) remained undegraded even after 30 min of ischemia. The undigested part largely reflected the extra amount of glycogen accumulated after the initial insults. It is discussed whether this part is unavailable to degradation by phosphorylase.
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PMID:Glycogen accumulated in the brain following insults is not degraded during a subsequent period of ischemia. 912 Apr 90


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