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

A computer technique for determination of the distribution of adenine nucleotides among compartmented, protonated, and metal-chelated species has been developed for the perfused rat heart. This procedure requires knowledge of tissue levels of creatine, creatine phosphate, ATP, ADP, and AMP and the glycolytic and respiration rates. The method is applicable to any physiological state of the organ and has been applied to transient behavior in aerobic, anoxic, and ischemic hearts. The results suggest that ADP uptake and ATP export by mitochondria are normally linked and equal in rate during aerobic metabolism or short-term anoxia but become separate and unequal during ischemia, so that mitochondrial adenine nucleotides, primarily AMP, accumulate.
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PMID:Distribution of adenine nucleotides in the perfused rat heart. 1 1

Changes in cerebral cortex concentrations of high-energy phosphates, glycolytic metabolites, citric acid cycle intermediates, associated amino acids, and ammonia, were studied after 5, 15 and 30 min of incomplete ischemia in rats anesthetized with 70% N2O or 150 mg.kg-1 of phenobartibal. Previous results have shown that with this type of ischemia (bilateral carotid artery occlusion combined with reduction in blood pressure to 50 mm Hg) cortical blood flow is reduced to below 10% of nitrous oxide values, whether animals are anesthetized with 70% N2O or 150 mg.kg-1 of phenobarbital. In animals under 70% N2O, changes in tissue concentrations of phosphocreatine, ATP, ADP and AMP were similar to those previously obtained in complete ischemia. However, some glucose remained in the tissue, and the lactate concentrations gradually rose to reach excessive values. Changes occuring in glycolytic and citric acid cycle intermediates were similar to those seen in complete ischemia but, after 30 min, there was some reduction in the pool size of amino acids. In those animals given phenobarbital and which lost all EEG activity during ischemia, changes in cerebral metabolites were virtually identical to those observed in nitrous oxide-anesthetized animals. However, some animals exposed to 5 or 15 min of ischemia had some remaining EEG activity. In these, cerebral energy state was significantly less deranged, and levels of glycogen, glucose and pyruvate were higher.
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PMID:Effects of phenobarbital in cerebral ischemia. Part I: cerebral energy metabolism during pronounced incomplete ischemia. 2 84

Bilateral occlusion of common carotid arteries in Mongolian gerbils was produced for the periods (up to 15 min) which were shown to be totally reversible. There was an initial increase of cyclic AMP and GABA levels and enhanced activities of adenylate cyclase and glutamate decarboxylase, as well as the reduction of norepinephrine level and decreased activities of monoamine oxidase, GABA-transaminase and Na+-K+-ATPase. Following these changes, decreased concentration of dopamine, serotinin and glutamate were found. The activities of total protein kinase and acetylcholinesterase were found to be reduced after longer periods of short-term ischemia. The data are consistent with the concept of increased non-controled release of putative neurotransmitters in ischemia.
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PMID:Alterations of putative neurotransmitters and enzymes during ischemia in gerbil cerebral cortex. 3 75

When keratome-sliced pig epidermis was floated on Hank's balanced salt solution, we observed a rapid decrease in the intracellular level of cyclic GMP. A portion of the lost cyclic GMP was detected in the incubation medium. When the epidermis was kept in air at room temperature, the cyclic GMP level also decreased rapidly but to a lesser degree. Incubating the epidermal slice at 37 degrees C in Hank's balanced salt solution with the addition of 3-isobutyl-1-methyl xanthine (IBMX) prevented the decrease. Also, after the cyclic GMP level had fallen, it could be raised to be the in vitro level by the addition of IBMX. Increased amounts of cyclic GMP were detectable in the medium in this case. These data indicate that the decrease in cyclic GMP in ischemic epidermis is due to sudden activation of epidermal cyclic GMP-phosphodiesterase and also in part due to leakage of cyclic GMP extracellularly. In contrast to the rapid decline in the cyclic GMP level, ischemia caused a rapid and transient increase in epidermal cyclic AMP. This confirms previous data by ourselves and by others (Br J Dermatol 92: 249-254, 1975; J Invest Dermatol 68:125-127, 1977). These "ischemic effects" must be avoided in order to measure the "in vivo level" of cyclic nucleotides in epidermis.
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PMID:Cyclic GMP System in epidermis: I. Effect of ischemia. 8 73

The effects of ischemia on myocardial adenine nucleotide metabolism and coronary flow during cardiac hypertrophy were studied in 140 rats and 20 guinea pigs, respectively. During increased periods of ischemia, the initially lower ATP contents decreased significantly as did the initially elevated ADP levels, whereas AMP, adenosine, and inosine, and hypoxanthine showed a continually rising elevation compared with the normal hearts. The sum of ATP, ADP, AMP, and their degradation products in the hypertrophied myocardial tissues started to decline after 5 min of ischemia. The remainder was found in the 0.9% NaCl solution in which the rat hearts were incubated, in the form of hypoxanthine, which was the largest fraction, followed by inosine and adenosine, which was the lowest fraction. In normal hearts, these changes occurred only after 60 min of ischemia. The coronary flow of the isolated guinea pig hearts increased significantly with decreasing content of the oxygen gas phase in the Krebs-Henseleit perfusion medium. These changes were more significant in normal than in hypertropheid hearts despite the clear initial elevations of the coronary flow in these hearts at 95% oxygen saturated perfusion, as well as the essential increases of the adenosine content in the myocardial tissues and in the perfusates during the development of the hypoxemia. Consequently, these results significantly demonstrate the curtailed compensation possibilities of hypertrophied hearts for the maintenance of their functions during the development of ischemia in comparison with normal hearts, a factor obviously caused by the ineffecient utilization of their energy supply even without ischemia.
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PMID:Effects of ischemia on adenine nucleotide metabolism and coronary flow during cardiac hypertrophy. 12 92

The activity of adenylate cyclase and the steady state levels of cyclic AMP (cAMP) were determined in stria vascularis (SV) and organ of Corti (OC) of the guinea pig cochlea. The activities are 12 and 19 pmoles/mg dry weight/minute for OC and SV, respectively. The activity was increased two to four-fold by NaF. The base level of cAMP is 4.2 and 4.4 nmoles/g dry weight in OC and SV, respectively. In contrast to brain, neither ischemia nor barbiturates produced major changes of the steady state levels of cAMP. No in vitro effect of cAMP upon the state of activation of glycogen phosphorylase was noticeable in either tissue. cAMP did not exert a significant in vitro inhibition of strial Na+K+-ATPase. Perilymphatic perfusion of cAMP (10-3 M) and of theophylline (5 times 10-3 M) did not produce changes in the endolymphatic potential (EP), but dibutyryl cAMP (10-3 M) led to a significant increase of EP. The alpha adrenergic blocking agent, phentolamine, produced very complex changes of the cochlear potentials. A possible role of catecholamines and cAMP in the secretory phenomena of the SV and in the transduction and/or transmission processes of the auditory sense organ are discussed.
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PMID:Cyclic AMP and adenylate cyclase in the inner ear. 16 45

Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the 'carrier-facilitated' transport mechanism. For glucose this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate-limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production and therefore, maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. An insulin-induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate.
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PMID:Insulin: fundamental mechanism of action and the heart. 18 67

By use of highly sensitive radioimmunoassays, 3':5'-cyclic AMP (cAMP) and 3':5'-cyclic GMP (cGMP) were measured in individual layers of light- and dark-adapted rabbit retinas, and the effects of ischemia were determined. In light-adapted retinas, cGMP levels ranged 50-fold, with over 90% of the total concentrated in the photoreceptor cells. The layer of outer segments contained 95 mumol/kg of dry weight, or three times the concentration present in the remainder of the photoreceptor cell layers. By contrast, levels of cAMP varied only 4-fold; the lowest level (6 mumol/kg of dry weight) was found in the outer segment layer and the highest level (22 mumol/kg of dry weight) in the inner segment layer of the photoreceptor cells. Dark adaptation elevated cGMP levels only in retinal layers containing photoreceptor cells, and the greatest proportional increase was observed in the synaptic layer of photoreceptor cells. Dark adaptation also caused increases of cAMP that were restricted to the outer plexiform and outer nuclear layers. Ischemia lowered cGMP levels, but only in retinal layers containing photoreceptor cells, and elevated cAMP levels, primarily in the inner layers of the retina. The effects of ischemia were greater in the dark-adapted than in light-adapted retinas. These results indicate that cGMP and cAMP levels in retina are influenced by the light adaptational state, that ischemia markedly modifies these processes, and that the effects of both light exposure and ischemia are regionally selective.
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PMID:Distribution of 3':5'-cyclic AMP and 3':5'-cyclic GMP in rabbit retina in vivo: selective effects of dark and light adaptation and ischemia. 18 39

After prelabeling the adenine nucleotides (ATP, ADP, AMP) of isolated perfused guinea pig hearts with either 14C-adenine or 14C-adenosine for 35 min, labeled adenosine, inosine, hypoxanthine and cyclic 3'5'-AMP (cAMP) were continuously released into the cardiac perfusate. Determination of the specific activities (SA) of the adenine nucleotides, cAMP, and their breakdown products (adenosine, inosine, hypoxanthine) in tissue and perfusate revealed: Under steady state conditions the SA of adenosine and cAMP in the perfusate were of the same order of magnitude and proved to be many times higher than the SA of the respective precursor adenine nucleotides. This difference was observed regardless whether adenine or adenosine was used as prelabeling substances. The SA of inosine and hypoxanthine in the perfusate were constantly lower than the SA of adenosine. Cardiac ischemia of 6 min, which resulted in a markedly increased formation of adenosine, led to a pronounced decrease in the SA of adenosine released from the heart. Our findings provide evidence that at least two different adenine nucleotide compartments of the heart severe as precursors for the formation of adenosine and cAMP, one characterized by a high, the other by a lower SA. Under normoxic conditions adenosine and cAMP released into the cardiac perfusate are derived mainly from a nucleotide fraction of high SA, which appears to be rather small. During ischemia a second compartment of much lower SA in addition contributes to the formation of adenosine.
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PMID:Compartmentation of cardiac adenine nucleotides and formation of adenosine. 18 85

It has recently been suggested that adenosine is a metabolic coupling factor responsible for an increased cerebral blood flow during hypoxia or increased functional activity. However, tissue adenosine concentrations have been reported to increase in situations previously shown to be unassociated with changes in tissue AMP concentrations. The present experiments were undertaken to assess cerebral cortex concentrations of adenosine under normal circumstances, and to relate changes in adenosine, AMP and cyclic AMP during shortlasting ischemia. Following freezing and extraction of tissue, adenosine was measured using high pressure liquid chromatography. In paralyzed and anaesthetized (70% N2O) rats, freezing of tissue through intact skull bone gave an adenosine concentration of 0.9 +/- 0.1 mumol-kg-1 (mean +/- S.E.M.). With freezing through the exposed dura the concentration was 3 times as high with a large scatter. When special precautions were taken to avoid tissue trauma during craniotomy, the adenosine concentration was 1.1 +/- 0.1 mumol-kg-1. It is concluded that previously reported values are erroneously high. During the first 60 s of total ischemia there was a linear correlation between increase in AMP and in adenosine concentration (as well as between adenosine and cyclic AMP concentrations). It is concluded that increases in tissue adenosine concentration only occur if AMP accumulates. However, since (relative) changes in adenosine concentrations are at least twice those of AMP, analyses of adenosine may provide sensitive measures of a change in phosphorylation state.
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PMID:Adenosine in rat cerebral cortex: its determination, normal values, and correlation to AMP and cyclic AMP during shortlasting ischemia. 19 47


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