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

We have studied the localization of osmium reduction products to investigate the functional state of organelles as well as organelle interrelationships during cell injury. In normal hepatocytes osmium deposits of variable intensity are seen in nuclear envelope, endoplasmic reticulum. Golgi cisternae and vesicles and lysosomes. Buffering of osmium with s- collidine (pH 7.4) prevents the deposition of osmium. Reversible (30 min) and irreversible (60 min) ischemia without reflow causes no change in the pattern of osmium deposition. Irreversible ischemia followed by reflow causes decreased staining of endoplasmic reticulum (ER) and redistribution of the osmium deposits through the cytoplasm. Reversibly injured pancreatic acinar cells in cultured explants manifest a similar loss of osmium staining in the endoplasmic reticulum cisternae. The administration of antimicrotubule drugs induces an accentuation of osmium staining in localized cisternal elements of hepatocytes. These heavily stained cisternae appear to give rise to the bounding membranes of drug-induced autophagic vacuoles. Cytoplasmic organelles sequestered inside the autophagic vacuoles acquire intense staining when they begin to undergo degradation. In homogenized liver tissue all the subcellular organelles show osmium deposits. The deposits are preferentially localized along the organelle membranes. In particular the dense deposits in the ER lumen are not seen in the subcellular fractions. Phospholipase A2 (3 units/mg protein) enhances the deposition of osmium in the lumen of microsomal vesicles, whereas the presence of detergent has no such effect. Addition of EDTA to the homogenizing medium enhances the ultrastructural preservation of the subcellular fractions but has little effect on the deposition of osmium. OsO4 deposition occurs at acid pH and the intensity and pattern of the stain can be modified in vivo and in vitro. Osmium tetroxide deposition is induced at sites of membrane transformation (autophagic vacuoles) and degradation (lysosomes). Calcium influx and phospholipase activation (ischemia, tissue homogenization, phospholipase addition) enhance osmium deposition and/or influence the localization of the staining pattern.
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PMID:Unbuffered osmium staining of cell organelles: alterations induced by cell injury. 620 40

We have studied calcium exchanges and mechanical function in heart muscle during and after a period of ischaemia. The experimental preparation was the isolated but arterially perfused interventricular septum of the rabbit. Uptake of calcium was measured with 47Ca2+ and efflux with 45Ca2+. 51Cr-EDTA was used as a marker of the extracellular space. Ischaemia caused a rapid decline of developed tension followed by a rise in resting tension. Tissue counts of 47Ca2+ decreased due to a reduction in the extracellular space. On reperfusion after ischaemia developed tension partially recovered and resting tension increased further before returning towards control values. A large and prolonged uptake of 47Ca2+ occurred immediately on reperfusion while 45Ca2+ efflux rose transiently. The uptake of calcium was related to the severity and duration of ischaemia and to the degree of mechanical recovery. Calcium accumulation on reperfusion is due to an increased influx which is not related to gross disruption of the cell membrane but more probably to a specific abnormality of ionic channels.
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PMID:Effects of ischaemia and reperfusion on calcium exchange and mechanical function in isolated rabbit myocardium. 679 Jan 71

The ability of hypothermia (34 degrees, 28 degrees) to preserve cardiac metabolism and performance during ischemia, was evaluated in the isolated Langendorff perfused rabbit heart. The hearts, isolated and perfused aerobically for 20', were made ischemic for 90' and their wall temperature maintained either at 37 degrees, 34 degrees and 28 degrees. The hearts were consequently reperfused at 37 degrees for 30'. Some of the hearts were frozen and assayed for ATP and CP. Others were homogenized and their mitochondria harvest, using either an EDTA free or an EDTA-containing extraction medium. The oxidative phosphorylating and ATP generating capacity of these mitochondria were established and their Ca++ content determined. The mechanical performance of the hearts, which were paced, was monitored by means of an intra-ventricular balloon filled with water and connected with a pressure transducer. The hearts that were made ischemic and maintained at 37 degrees were severely depleted in ATP and CP content, their mitochondria accumulated Ca++ and their oxidative phosphorylating activity was impaired. During reperfusion mitochondrial Ca++ was substantially increased, the capacity of the mitochondria to use O2 for state III respiration was further impaired and their ATP generating capacity reduced. Diastolic pressure increased and there was no recovery of the ability of the hearts to develop sistolic pressure. The hearts made ischemic and maintained at 28 degrees were protected. There was a less marked rise in mitochondrial Ca++ concentration after ischemia and during reperfusion; the mitochondria recovered the capacity of utilizing O2 and of generating ATP. That was coincident with and almost complete recovery of mechanical performance. Hypothermia at 34 degrees during ischemia provoked only a partial protection. These results are discussed in accordance with the hypothesis that hypothermia protects heart muscle against the deleterious effects of ischemia not only by reducing the metabolic requirement but also by maintaining intracellular homeostasis with respect to Ca++.
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PMID:[Effect and action mechanism of hypothermia to preserve the ischaemic myocardium (author's transl)]. 720 98

To determine the relative influence of two levels of ischemia on myocardial cation and water composition as well as cardiac function, intact anesthetized dogs were studied for 1 h using a balloon-tip catheter in the proximal left anterior descending coronary artery. Hemodynamic studies in group A revealed a diminished ejection fraction during mild and severe ischemia associated, respectively, with a 36% and 74% decline in transmural coronary flow. Left ventricular end diastolic pressure rose only after severe ischemia. Greater accumulation of sodium and water and loss of K+ in ischemic tissue was observed in animals with severe ischemia. In group B, intracellular cations and water were estimated on the basis of 51Cr-labeled EDTA distribution. The extracellular space was unaltered at either level of ischemia. During mild ischemia, cell Na+ and H2O were enhanced in the inner and outer layers of myocardium. Despite a 25% reduction in subendocardial blood flow by the labeled microsphere technique, K+ content was normal. After severe ischemia, cell K+ was reduced in inner and outer layers. However, the increase of cell Na+ content substantially exceeded K+, suggesting a major effect on the sodium pump or cell permeability.
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PMID:Dissociation of myocardial sodium and potassium alterations in mild versus severe ischemia. 737 31

Whereas the changes of calcium influx and net calcium content in the myocardium have been described during ischemia, less is known of the changes that occur during and after hypoxia. In this study calcium uptake was measured with 47Ca2+, a high energy gamma emitter, calcium efflux with both 47Ca2+ and 45Ca2+, and extracellular space with 51Cr-EDTA. The experimental preparation was the isolated but arterially perfused interventricular septum of the rabbit. Temperature was 32 degrees C. Hypoxia in the absence of substrate caused a fall in developed tension and rise in resting tension. After 30 min, recovery on reoxygenation was incomplete. During hypoxia without substrate small changes of the extracellular space were associated with changes of mechanical function. Calcium efflux did not alter. Calcium influx decreased during the initial 30 min, but after 60 min a small increase was evident. The tissue content of 51Cr-EDTA only increased after prolonged hypoxia, suggesting that the increase of calcium influx at this time was due to nonspecific damage to the cell membrane. On reoxygenation calcium efflux was unaltered, but a large incrase of calcium influx occurred without an associated influx of 51Cr-EDTA. The influx of calcium on reoxygenation appears, therefore, to be caused by a relatively specific abnormality of the calcium transport system and not by generalized destruction of the cell membrane.
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PMID:Continuous measurement of 47Ca2+ uptake during and after hypoxia in rabbit myocardium. 742 45

Acidosis (pH 6.0) led to significant decrease in high-affinity choline uptake by rat brain synaptosomes. The effects persisted following pH readjustment (7.4) of the incubation medium, consisting of decrease in both Km and Vmax of the affinity system. pH readjustment coincided with synaptosomal leakage of lactate dehydrogenase (LDH) and with instability of the synaptosomal suspension as evidenced from turbidity modifications of the preparation. LDH leakage occurred when acidosis was performed with lactic acid, whereas it was not seen following H3PO4 acidosis, probably because of the rapid diffusion of the protonated from of lactic acid across membranes. Turbidity modifications of the suspension were prevented by EDTA. The present results indicate that acidosis to pH level comparable to what is observed in brain ischemia is deleterious for cholinergic mechanisms. They also suggest that alkaline pH shifts that occur after blood reperfusion of ischemic brain tissue might be critical for the survival of cells.
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PMID:Acidosis-induced modifications of high-affinity choline uptake by synaptosomes: effects of pH readjustment. 747 80

The role of gastric mucus was evaluated in a rat model of gastric epithelial damage induced by local ischemia/reperfusion (I/R) stress. In this model, blood-to-lumen chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) clearance served as an index of injury. Tetraprenyl acetone (TPA; 100 mg, 200 mg/kg IP) was used to stimulate mucus production. Administration of TPA increased both the hexosamine content in gastric tissue and the amount of alcian blue-periodic acid Schiff (AB-PAS) stained mucus in the mucosa in a dose-dependent manner. Increases in 51Cr-EDTA clearance induced by I/R were significantly attenuated by TPA in a dose-dependent manner. N-acetyl-L-cysteine (NAC; 0.6%, 0.8%) was perfused into the gastric lumen to assess the effect of reduction in mucus on the injury induced by I/R. Although mean values of hexosamine content were increased by perfusion with NAC, AB-PAS-stained mucus in the mucosa was significantly decreased in a dose-dependent manner. Perfusion of NAC did not change basal 51Cr-EDTA clearance but significantly exacerbated the increase in clearance induced by I/R in a dose-dependent manner. These results indicate that gastric mucus protects the gastric mucosa against I/R stress in vivo.
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PMID:Role of mucus in gastric mucosal injury induced by local ischemia/reperfusion. 766 77

Copper Fenton systems (Cu(II)/H2O2 and Cu(II)/Asc) inactivated the lipoamide reductase and enhanced the diaphorase activity of pig-heart lipoamide dehydrogenase (LADH). Cupric ions alone were less effective. As a result of Cu(II)/H2O2 treatment, the number of titrated thiols in LADH decreased from 6 to 1 per subunit. NADH and ADP (not NAD+ or ATP) enhanced LADH inactivation by Cu(II). NADH also enhanced the effect of Cu(II)/H2O2. Dihydrolipoamide, dihydrolipoic acid, Captopril, acetylcysteine, EDTA, DETAPAC, histidine, bathocuproine, GSSG and trypanothione prevented LADH inactivation. 100 microM GSH, DL-dithiothreitol, N-(2-mercaptopropionylglicine) and penicillamine protected LADH against Cu(II)/Asc and Cu(II), whereas 1.0 mm GSH and DL-dithiothreitol also protected LADH against Cu(II)/H2O2. Allopurinol provided partial protection against Cu(II)/H2O2. Ethanol, mannitol, Na benzoate and superoxide dismutase failed to prevent LADH inactivation by Cu(II)/H2O2 or Cu(II). Catalase (native or denaturated) and bovine serum albumin protected LADH but that protection should be due to Cu binding. LADH inhibited deoxyribose oxidation and benzoate hydroxylation by Cu(II)/H2O2. It is concluded that site-specifically generated HO, radicals were responsible for LADH inactivation by Cu(II) Fenton systems. The latter effect is discussed in the context of ischemia-reoxygenation myocardial injury.
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PMID:Inactivation of heart dihydrolipoamide dehydrogenase by copper Fenton systems. Effect of thiol compounds and metal chelators. 775

The objective of this study was to determine whether the nitric oxide (NO) donors, spermine NO and 3-morpholinosydonimine-N-ethyl-carbamide (SIN1), alter the mucosal and microvascular responses of the feline small intestine to 6 hr of hypothermic ischemia and 2 hr of normothermic reperfusion. Intestinal mucosal permeability was monitored using the blood-to-lumen clearance of 51Cr-EDTA. Lymph flow and lymphatic protein clearance estimates were used to assess intestinal microvascular fluid filtration and vascular protein leakage, respectively. Spermine NO (0.1 mmol/L) or SIN1 (0.5 mmol/L) was added to the luminal perfusate during the entire reperfusion period. Both NO donors were effective in attenuating the increased mucosal permeability to 51Cr-EDTA and the depressed net water absorption, relative to untreated intestinal preparations exposed to the same protocol. Intestinal lymph flow, lymphatic protein clearance, and capillary hydrostatic pressure were increased by a greater extent in preparations treated with spermine NO. These findings suggest that NO donors may improve mucosal function in intestinal allografts subjected to prolonged hypothermic ischemia. This protective effect on mucosal epithelium appears to be unrelated to an action of the NO donors on the microvasculature.
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PMID:Nitric oxide donors improve gut function after prolonged hypothermic ischemia. 788 92

Rapid depression of Ca(2+)-uptake by sarcoplasmic reticulum (SR) vesicles and inhibition of the activity of creatine kinase (CK) and pyruvate kinase (PK) was observed during incubation of enzymes with micromolar concentrations of iron in the presence of adenine nucleotides. This effect of iron was dependent on the redox state of the iron as determined by the redox state of the environment. Redox conditions that generated an Fe2+/Fe3+ ratio close to 1 were most effective in depressing Ca(2+)-uptake by SR vesicles. Redox conditions that decreased the Fe2+/Fe3+ ratio by oxidizing iron were most effective in depressing CK activity while redox conditions that significantly increased the Fe2+/Fe3+ ratio by reducing iron were most effective in depressing PK activity. All iron sensitive enzymes possessed N-etylmaleimide (NEM) sensitive sulphydryl groups that are essential for their activity. The sensitivity to inhibition by NEM increased in the order: PK < Ca(2+)-uptake < CK. Iron initiated depression of CK and PK activities were reversible with dithiothreitol (DTT). This indicated that modification of SH groups was an important step in the mechanism by which iron depressed enzyme activity. Iron initiated depression of Ca(2+)-uptake and of the activity of CK and PK was prevented by not allowing the critical Fe2+/Fe3+ ratio to be reached and by binding of iron with desferroxamine and EDTA. These results, together with data from the literature, led us to suggest that changes in the redox state of cellular micro-environments, inevitably taking place during ischemia and reperfusion, may increase the availability of "low molecular weight iron" and, through changes in the redox state of this iron, selectively initiate reversible depression of several enzymes which contain SH groups essential for their activity.
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PMID:Iron effects on myocardial enzymes depend on redox state. 800 76


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