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Query: UMLS:C0003129 (Anoxia)
 551 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of glucose concentration and anoxia upon the metabolite concentrations and rates of glycolysis and respiration have been investigated in the perfused liver of the fetal guinea pig. In most cases the metabolite concentrations in the perfused liver were similar to those observed in vivo. Between 50 days and term there was a fall in the respiratory rate and in the concentration of ATP and fructose 1,6-diphosphate and an increase in the concentration of glutamate, glycogen and glucose. Reducing the medium glucose concentration from 10 mM to 1 mM or 0.1 mM depressed lactate production and the concentration of most of the phosphorylated intermediates (except 6-phosphogluconate) in the liver of the 50-day fetus. This indicates a fall in glycolytic rate which is not in accord with the known kinetic properties of hexokinase in the fetal liver. Anoxia increased lactate production by, and the concentrations of, the hexose phosphates ADP and AMP in the 50-day to term fetal liver, while the concentration of ribulose 5-phosphate, ATP and some triose phosphates fell. These results are consistent with an activation of glycolysis, particularly at phosphofructokinase and of a reduction in pentose phosphate pathway activity, particularly at 6-phosphogluconate dehydrogenase. The calculated cytosolic NAD+/NADH ratio for the perfused liver was similar to that measured in vivo and evidence is presented to suggest that the dihydroxyacetone phosphate/glycerol 3-phosphate ratio gives a better indication of cytosolic redox than the lactate/pyruvate ratio. The present observations indicate that phosphofructokinase hexokinase and possibly pyruvate kinase control the glycolytic rate and that glyceraldehyde-3-phosphate dehydrogenase is at equilibrium in the perfused liver of the fetal guinea pig.
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PMID:Some effects of glucose concentration and anoxia on glycolysis and metabolite concentrations in the perfused liver of fetal guinea pig. 2 74

Anoxia has been compared with ischaemia. The abrupt restoration of either oxygen of flow may accelerate cardiac damage. Anoxic stimulation of glycolysis (Pasteur effect) is inhibited during ischaemia by lactate and proton accumulation at the levels of phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. Anaerobic glycolysis provides lactate and ATP; breakdown of the latter provides protons. During partial respiration thought to occur in partial ischaemia, continued production of CO2 is a factor contributing to intracellular acidosis; mitochondrial ATP when formed by continued respiration also yields protons when ultimately broken down. The endoproducts of aerobic glycolysis (pyruvate and NADH) are transported into the mitochondria by the malate-aspartate cycle and by pyruvate dehydrogenase activity. Adenine nucleotide transferase activity normally transfers the mitochondrially-made ATP to the cytoplasm, but acyl CoA accumulates in ischaemia (or during perfusions with high circulating free fatty acids) to inhibit the transferase. The mitochondrial creatine kinase is thought to transform ATP transported outwards into creatine phosphate which can permeate the outer mitochondrial membrane. Further compartmentation of ATP may be by other creatine kinase isoenzymes or in relation to the cell membrane. The glycogenolytic-sarcoplasmic reticulum complex links a glycogen pool to the sarcoplasmic reticulum. Cyclic AMP may regulate admission of calcium to the cell during the plateau of the action potential and promote calcium uptake by the sarcoplasmic reticulum by phosphorylation of phospholamban. The latter promotes the activity of the calcium-transport ATPase. Calcium and cyclic AMP may also interact at the level of the contractile proteins where cyclic AMP phosphrylates troponin. Cyclic GMP generally has opposite effects to cyclic AMP and undergoes opposite changes in the frog cardiac cycle to those of cyclic AMP. A present it is reasonable to suppose that physiological effects of adrenaline or of cholinergic agents on the myocardium are mediated by cyclic AMP or cyclic GMP, respectively, but this hypothesis still lacks firm support. There is an association between tissue cyclic AMP and ventricular fibrillation after coronary ligation, and direct evidence for a role of cyclic AMP in promoting arrhythmias has been obtained by studies on the ventricular fibrillation threshold in the rat heart. However, there are other mechanisms, involving first the effects of substrates on the action potential duration, and secondly, the fast channel, which can also give rise to the development of malignant arrhythmias.
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PMID:Myocardial metabolism and heart disease. 3 41

Cellular high-energy phosphate levels and 42K exchange were studied in isolated, interventricular rabbit septa at 28 degrees C. Septa were perfused with a modified Tyrode solution that contained glucose as the metabolic substrate. Anoxia was induced by switching to solution equilibrated with N2-CO2 gas. Potassium lost during anoxia by increased efflux from the cells was measured by 42K. Whole tissue levels of ATP, ADP, phosphocreatine, and total creatine were determined. The effects of 20-min anoxic stresses were evaluated in each of four groups of septa: 1) control (perfused with regular solution and paced at 42 excitations/min; 2) E-C uncoupled (by perfusing with solution containing 50 micron Ca2+); 3) quiescent (spontaneous contraction rate less than 1/min); and 4) perfused with high glucose solution (20 mM). Compared to the control group, only quiescence significantly decreased the potassium loss during anoxia; the cellular energetic state was well maintained during stress by both E-C uncoupling and quiescence. The results indicate that the increase in potassium efflux during brief anoxic stress is largely excitation dependent and can be dissociated from contraction and cellular energetic state.
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PMID:Dissociation of energetic state and potassium loss from anoxic myocardium. 72 75

1. The mechanisms responsible for the depolarization of the hepatocytes secondary to anoxia have been studied in isolated perfused dog liver. It was attempted to elucidate the role of the inhibition of the sodium pump following exhaustion of the energy reserves and of the modifications of membrane permeability. Anoxia was compared to ouabain and to a reduction of the cellular ATP level. 2. Membrane potentials were measured with micro-electrodes. Potassium, sodium and chloride were determined in plasma samples and liver tissues. Extracellular space was measured with tritiated inulin or with an electrical impedance method. Adenine nucleotides were also measured in liver biopsies. 3. The fall in membrane potential produced by administration of ouabain (0-1 mM) is greater than the effect of the redistribution of sodium + potassium ions; this suggests that the sodium pump is functioning, at least partially, electrogenically. The administration of dinitrophenol (10 mM), which causes a 74% fall in the ATP level in 15 min, produces, as does ouabain, a depolarization which also corresponds to stopping an electrogenic pump. 4. A partial reduction in the level of ATP brought about by hypoxia, by an inhibitor of cellular respiration, antimycin (10 mM), or by fructose (20 mM) results in a hyperpolarization which may be attributed to an elevation of potassium permeability (PK) since it is concomitant to a loss of K from the liver. The change in membrane permeability could be related to a rise in the free calcium in the cells which has not been documented. Other possible hypothesis include a facilitated transport for potassium. 5. The administration of amobarbitone (10 mM) produces immediately a depolarization which is independent of the progressive reduction in the level of ATP. The depolarization has been attributed to a direct effect of amobarbitone on the membrane reducing the permeability for potassium ions. 6. The depolarization observed in ischaemic anoxia is greater than that produced by ouabain for the same variation in ions concentration. In addition to a likely inhibition of the electrogenic sodium pump, changes in membrane permeability inducing a rise in the PNa/PK ratio must also occur. 7. After ischaemic anoxia for 24 hr at 3 degrees C, the ratio of PNa/PK rises to 0-68 which indicates abolishment of the selective character of membrane permeability. The augmentation in cell volume produced by anoxia might result in an opening of membrane pores, which could entail the augmentation of sodium permeability; the latter would be responsible in part for the depolarization produced by anoxia. 8. According to the severity and length of oxygen deprivation an increase in PK, a cessation of the sodium pump activity and finally an increase in PNa will occur.
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PMID:Effect of anoxia and ATP depletion on the membrane potential and permeability of dog liver. 89 69

The effects were studied of hypoxia on intracellular ion activities in sheep heart Purkinje fibres. The intracellular pH (pHi), surface pH (pHs), intracellular potassium activity (aki), and intracellular sodium activity (aNai) of the cells were recorded using liquid ion exchanger-filled microelectrodes. Various methods of inhibiting oxidative phosphorylation were compared for their effect on pHi. These methods were the use of hypoxia, anoxia or NaCN (2 mM). Hypoxia was produced by degassing solutions under reduced pressure then bubbling with 100% nitrogen gas. Anoxia was produced in a similar manner but with the addition of the reducing agent sodium dithionite (0.5 mM) to remove all traces of oxygen from the solutions. Anoxia caused the most marked changes. Concentration of sodium dithionite between 0.1 and 1 mM produced similar maximum rates of acidification. High concentrations (5 or 20 mM) could produce larger intracellular acidifications apparently unrelated to anoxia. The effects of hypoxia and NaCN were similar. Inhibition of Na(+)-H+ exchange with amiloride (1 mM) had little effect on the pH changes produced by hypoxia. Periods of hypoxia exceeding 1 h still resulted in rapid, readily reversible changes in pHi. Hypoxia caused a rise in aNai, the effect being larger in anoxic conditions. The intracellular K+ activity decreased in hypoxia with further decreases in anoxic conditions. The intracellular ion changes produced during hypoxia are discussed in terms of the production of lactic acid by the cells and changes in the ATP supply to the Na(+)-K+ pump.
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PMID:Intracellular pH changes induced by hypoxia and anoxia in isolated sheep heart Purkinje fibres. 131 38

The effects of fructose on the intracellular ionic changes evoked by anoxia were studied in freshly isolated rat hepatocytes maintained in agarose gel threads and perfused with Krebs-Henseleit bicarbonate buffer (KHB). Cytosolic free calcium (Ca2+i) was measured with aequorin, intracellular sodium (Na+i) with sodium-binding benzofuran isophthalate, intracellular pH (pHi) with 2'-7'-bis(carboxyethyl)-5,6-carboxyfluorescein, lactic dehydrogenase (LDH) by the increase in NADH absorbance during lactate oxidation to pyruvate, and viability by trypan blue exclusion. ATP, Pi, phosphomonoesters, and the cell phosphorylation potential assessed by the reciprocal of the Pi/ATP ratio were measured by 31P NMR spectroscopy in real time. Intracellular free Mg2+ (Mg2+i) was calculated from the chemical shift of beta-ATP relative to alpha-ATP in the NMR spectra. Anoxia was induced by perfusing the cells with KHB saturated with 95% N2, 5% CO2. When the perfusate contained 5 mM glucose as substrate, anoxia caused a fall in ATP, a rise in Pi, and in the Pi/ATP ratio, a biphasic increase in Ca2+i that reached 1.45 +/- 0.42 microM and a 6-fold increase in LDH. When 15 mM fructose was used as substrate during the anoxic period, intracellular ATP decreased much faster than with glucose, Pi did not increase, and the concentration of phosphomonoesters increased 2.5-fold. During the first hour of anoxia, the Pi/ATP ratio was higher in the fructose than in the glucose group indicating that the hepatocyte phosphorylation potential and ATP decreased faster and to lower levels with fructose than with glucose. On the other hand, ATP and the phosphorylation potential of the fructose group increased during the second hour of anoxia, in contrast to their continuous decline in the glucose group. The major surge in Ca2+i was depressed 52% when glucose was replaced by fructose: Ca2+i reached only 0.7 +/- 0.2 microM instead of 1.45 +/- 0.42 microM (p less than 0.01). Anoxia also caused an increase in Na+i and an intracellular acidosis. The rise in Na+i was significantly greater with fructose than with glucose. Na+i rose from a control value of 15.9 +/- 2.4 to 32.2 +/- 0.4 mM with glucose and to 48.7 +/- 0.7 mM with fructose (p less than 0.001). The decrease in pHi from a control value of 7.43 +/- 0.03 was consistently greater and faster with fructose than with glucose: 6.59 +/- 0.03 and 7.04 +/- 0.01, respectively. At the same time, fructose completely suppressed LDH release and reduced the loss of viability produced by anoxia from 27.7 +/- 2.9 to 14 +/- 3.1% (p less than 0.05).
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PMID:Fructose protects rat hepatocytes from anoxic injury. Effect on intracellular ATP, Ca2+i, Mg2+i, Na+i, and pHi. 155 92

The effects of anoxia were studied in freshly isolated rat hepatocytes maintained in agarose gel threads and perfused with Krebs-Henseleit bicarbonate buffer (KHB). Cytosolic free calcium (Ca2+i) was measured with aequorin, intracellular sodium (Na+i) with SBFI, intracellular pH (pHi) with BCECF, lactic dehydrogenase (LDH) by the increase in NADH absorbance during lactate oxidation to pyruvate, ATP by 31P NMR spectroscopy in real time, and intracellular free Mg2+ (Mg2+i) from the chemical shift of beta-ATP relative to alpha-ATP in the NMR spectra. Anoxia was induced by perfusing the cells with KHB saturated with 95% N2, 5% CO2. After 1 h of anoxia, beta-ATP fell 66%, and 85% after 2 h, while the Pi/ATP ratio increased 10-fold from 2.75 to 28.3. Under control conditions, the resting cytosolic free calcium was 127 +/- 6 nM. Anoxia increased Ca2+i in two distinct phases: a first rise occurred within 15 min and reached a mean value of 389 +/- 35 nM (p less than 0.001). A second peak reached a maximum value of 1.45 +/- 0.12 microM (p less than 0.001) after 1 h. During the first hour of anoxia, Na+i increased from 15.9 +/- 2.4 mM to 32.2 +/- 1.2 mM (p less than 0.001), Mg2+i doubled from 0.51 +/- 0.05 to 1.12 +/- 0.01 mM (p less than 0.001), and pHi decreased from 7.41 +/- 0.03 to 7.06 +/- 0.1 (p less than 0.001). LDH release doubled during the first hour and increased 6-fold during the second hour of anoxia. Upon reoxygenation, ATP, Ca2+i, Mg2+i, Na+i, and LDH returned near the control levels within 45 min. To determine whether the increased LDH release was related to the rise in Ca2+i, and whether the increased Ca2+i was caused by Ca2+ influx, the cells were perfused with Ca(2+)-free KHB (+ 0.1 mM EGTA) during the anoxic period. After 2 h of anoxia in Ca(2+)-free medium, beta-ATP again fell 90%, but Ca2+i, after the first initial peak, fell below control levels, and LDH release increased only 2.7-fold. During reoxygenation, Ca2+i, ATP, Na+i, and LDH returned near the control levels within 45 min. These results suggest that the rise in Ca2+i induced by anoxia is caused by an influx of Ca2+ from the extracellular fluid, and that LDH release and cell injury may be related to the resulting rise in Ca2+i.
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PMID:Effect of anoxia on intracellular ATP, Na+i, Ca2+i, Mg2+i, and cytotoxicity in rat hepatocytes. 163 81

This communication describes the effects of anoxia on rabbit proximal renal tubule element (ion) content by using high-resolution electron probe x-ray microanalytical imaging to obtain quantitative elemental data from subcellular compartments not previously resolvable with low-resolution imaging. These organelles and regions include the heterochromatin and euchromatin of the nucleus and the microvilli of the apical brush border, in addition to mitochondria, lysosomes, and cytoplasm. Anoxia of 40-min duration caused the expected decrease in K and increase in Na and Cl concentrations in the tubules with the cytoplasmic K:Na ratio declining to 0.13:1. These changes were accompanied by decreases in ATP and total K contents, and an increase in lactate dehydrogenase release. Swelling occurred in some cells as evidenced by ultrastructural changes. No alterations were evident after oxygen deprivation in Ca content of cytoplasm (control, 6.7 +/- 0.6 versus anoxia, 7.6 +/- 0.7 nmol/mg dry wt) or mitochondria (control, 4.0 +/- 0.4 versus anoxia, 4.9 +/- 0.6 nmol/mg dry wt) or in S content of recognizable lysosomes (control, 314 +/- 11 versus anoxia, 325 +/- 12 nmol/mg dry wt). Brush border (microvillus) Ca content was higher than cytoplasmic Ca content during normoxia (10.7 +/- 0.9 nmol/mg dry wt) and increased further during anoxia (17.0 +/- 1.0 nmol of Ca/mg dry wt). The finding of higher Ca content within the brush border region during normoxia is unexpected and novel, because such results suggest that Ca homeostasis in the apical elaboration of the proximal cell may be different from that in the cytoplasm. The results also raise the possibility that an increase in Ca content in the brush border membrane region may be involved in the pathogenesis of renal cell injury.
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PMID:Elemental microanalysis of organelles in proximal tubules. II. Effects of oxygen deprivation. 191 94

In ischemic myocardium abnormal lipid metabolism results in accumulation of compounds that are deleterious to membrane structural integrity and membrane dependent functions. In this study isolated adult rat ventricular myocytes were used to investigate anoxia-induced alterations in cellular lipid composition and metabolism. Myocyte phospholipid content declined 19% on average during 60 min anoxia and intracellular arachidonic acid increased 3-fold, without affecting myocyte ATP content. Anaerobic incubation in the absence of glucose depleted cellular ATP to 2 nmol/mg protein, elicited a 23% decrease in phospholipids, and reduced triacylglycerol content by 51%. Intracellular levels of C16-C22 fatty acids were significantly elevated, especially palmitic and arachidonic acids. Myocytes presented with 0.08 mM [1-14C]-palmitic or arachidonic acid acylated 85% (25-26 nmol/mg) of the fatty acid taken up into triacylglycerols. Anoxia decreased this esterification by 46-60%. Formation of [14C]-CO2 was also depressed 70-90% by anaerobiosis. The results demonstrate that anoxia stimulates degradation of complex lipids, with a concomitant increase in non-esterified fatty acids, especially arachidonic acid.
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PMID:The effect of anoxia on lipid metabolism in isolated adult rat cardiac myocytes. 212 22

We used 31P-nuclear magnetic resonance (NMR) spectroscopy to measure intracellular pH (pHi) and high-energy phosphate levels in hearts of turtles (Chrysemys picta bellii) during either 4 h of anoxia [extracellular pH (pHo) 7.8, 97% N2-3% CO2], 4 h of lactic acidosis (pHo 7.0, 97% O2-3% CO2), or 1.5 h of combined anoxia + lactic acidosis (pHo 7.0, 97% N2-3% CO2) followed by 2 h of oxygenated recovery (pHo 7.8) at 20 degrees C. We also measured heart rate, maximum ventricular-developed pressure, and rate of pressure development (dP/dtmax). 31P-NMR spectra were characterized by the seven peaks typical of mammalian hearts, although turtle spectra were dominated by a large phosphodiester peak. Anoxia caused an increase in Pi to 165% and a decrease in creatine phosphate (CP) to 42% of control, whereas ATP levels remained unchanged. pHi declined from 7.37 +/- 0.01 to 7.22 +/- 0.03 at 1 h of anoxia and remained unchanged through hour 4. Lactic acidosis caused a 59% decrease in Pi, whereas CP and ATP levels remained unchanged. pHi fell to 6.88 +/- 0.04 by hour 1 and then climbed steadily to 7.14 +/- 0.05 at hour 4. During recovery from acidosis, pHi exceeded control values and returned to control by 2 h. Combined anoxia + acidosis caused profound decreases in CP to 14% and pHi to 6.56 +/- 0.03. In anoxic hearts, cardiodynamic variables remained at control levels through hour 3, after which cardiac output, heart rate, and dP/dtmax declined. Cardiodynamic variables were essentially unchanged from control throughout 4 h of acidosis except for dP/dtmax, which declined rapidly. In the combined protocol, all measures of cardiac function decreased. Recovery in all three cases was complete by approximately 2 h. We conclude that turtle hearts were relatively resistant to the stresses imposed in all three protocols compared with mammalian hearts, although anoxia + acidosis depressed the measured cardiac variables more profoundly than predicted from responses to the conditions imposed separately. Our results from the anoxia protocol suggest no direct causal relationship between myocardial CP (or ATP) levels and cardiac function.
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PMID:31P-NMR measurements of pHi and high-energy phosphates in isolated turtle hearts during anoxia and acidosis. 239 11


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