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

In isolated adult rat myocytes, we tested the hypothesis that metabolic inhibition and simulated ischemia regulate the NADH/NAD+ redox couple with concomitant impairment of energy-dependent process, including contraction and maintenance of high-energy phosphate stores. We developed a method to examine the relationship among the redox couple, ATP content, and contractile performance in single cells under several conditions analogous to myocardial ischemia, with and without reperfusion. Myocytes were paced at 1 Hz while cell contraction and NADH fluorescence were determined simultaneously for single cells at 37 degrees C. Cells were exposed to cyanide and 2-deoxy-D-glucose (metabolic inhibition) or to metabolic inhibition plus 12 mM KCl and 20 mM lactate at pH 6.5 (simulated ischemia). Pyridine nucleotide fluorescence signals from single cells studied in this fashion could be modulated by metabolic inhibitors in a manner similar to that classically described for isolated mitochondria. Metabolic inhibition or simulated ischemia quickly produced maximal reduction of NAD+ to NADH. When cells were exposed to simulated ischemia for 10 min, then superfused with glucose-containing control buffer, 28% of cells exposed to conditions of simulated ischemia developed hypercontracture on reperfusion. Hypercontracture developed despite mitochondrial electron transport being reestablished. When myocyte suspensions in a cuvette were studied spectrofluorimetrically, the pyridine nucleotide fluorescence response to metabolic inhibitors was similar to that for a single cell. This permitted correlation of ATP determinations on cells in suspension with contractile and fluorescence measurements from single myocytes. In the absence of glycolysis there is correspondence among loss of electron transport, decline in high-energy phosphate concentration, and decline in contraction. Irreversible disruption of the electron transport process does not appear to be an early event in ischemic injury.
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PMID:NADH measurements in adult rat myocytes during simulated ischemia. 205 13

The brain ischemia of spontaneously hypertensive rat was produced gradually by bilateral ligation of the common carotid arteries. The cortical blood flow was measured with a laser doppler flowmeter before and after ligation of the arteries. At the specified intervals, the brain was frozen in situ with liquid nitrogen. The concentration of blood glucose and glycolytic intermediate in frozen brain were measured and the relationship between glycolytic activity and the concentrations of effectors to PFK-1, such as fructose 2,6-bisphosphate, fructose 1,6-bisphosphate, AMP, ATP, Pi and citrate, was investigated. The changes in glycolytic intermediates, pyridine and adenine nucleotides concentration showed that ischemic change occurred in the brain tissue after 30 min of bilateral ligation of the common carotid arteries, in correlation with the decrease in cortical blood flow. The rate of lactate formation increased during the 30-60 min interval and finally decreased during 60-120 min period of ischemia. This indicates that anaerobic glycolysis was accelerated during the early stages of ischemia. The most potent activator of PFK-1, fructose 2, 6-bisphoshate, increased from 5.3 or 6.7 nmol g during the initial stage of ischemia, and this change preceded the activation of glycolysis and the increase in fructose 1,6-bisphosphate concentration, a result indicated that fructose 2,6-bisphosphate does participate in the activation of glycolysis during brain ischemia in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Glycolytic activity and fructose 2, 6-bisphosphate changes in rat brain during ischemia]. 214 15

Brain ischemia was produced by bilateral ligation of the common carotid arteries of spontaneously hypertensive rats. The concentrations of fructose 2,6-bisphosphate and other glycolytic intermediates as well as of pyridine and adenine nucleotides were measured in frozen brain samples. In contrast to the decrease reported in hepatocytes under anoxic conditions, the fructose 2,6-bisphosphate content was increased by 20-30% during the early stages of ischemia. Elevation in fructose 1,6-bisphosphate level and lactate formation followed the rise in fructose 2,6-bisphosphate content, a finding suggesting that this compound plays a key role in the compensatory acceleration of glycolysis under ischemic conditions in vivo.
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PMID:Fructose 2,6-bisphosphate changes in rat brain during ischemia. 215 55

Hypoxia and ischemia are potent stimuli to vascular growth. The mechanisms by which vascular growth is induced are unknown. During ischemia, such as that which occurs in the heart, purine and pyridine nucleotides are degraded and their metabolites accumulate. At least two of these metabolites, adenosine and nicotinamide, have previously been demonstrated to induce vascular growth. The goal of this study was to determine whether other purine and pyridine metabolites have the potential to stimulate angiogenesis in vivo, to determine the relative angiogenic potency of these metabolites, and to determine if their angiogenic effects is mediated through a direct effect on endothelial cell proliferation. Purine metabolites (adenosine, inosine, hypoxanthine, xanthine, guanosine, uric acid), the pyridine metabolite nicotinamide, and chemical derivatives of nicotinamide, were tested at various concentrations for their ability to stimulate angiogenesis in the chick choriollantoic membrane assay. Although none of the purine metabolites were effective in promoting the angiogenic response, nicotinamide as well as several derivatives of nicotinamide induced an angiogenic response in a dose-dependent manner. Nicotinamide was then evaluated to determine if its angiogenic effect is a result of a direct effect on capillary endothelial cell proliferation. In concentrations of 100 microM to 1 mM nicotinamide was not demonstrated to be mitogenic for bovine capillary endothelial cells. These results demonstrate that pyridine nucleotides are indirect angiogenic agents that do not exert a primary effect on endothelial cell proliferation. The results of this study suggest that increases in vascular growth induced by ischemia and hypoxia might be mediated, at least in part, by pyridine metabolites released from ischemic tissues.
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PMID:Angiogenic potency of nucleotide metabolites: potential role in ischemia-induced vascular growth. 252 26

Brain levels of NADH and NAD+ were measured in three models of cerebral ischemia to determine whether degradation of the pyridine nucleotides is enhanced in models that generate high concentrations of lactic acid. Complete ischemia (decapitation), in which lactate increased to 14 mmol/kg, caused a gradual decrease in the NAD pool to 50% of control by 2 h. During focal ischemia (occlusion of the middle cerebral artery), the decrease in the NAD pool was less pronounced (82% of control at 2 h) despite the accentuated accumulation of lactate to 33 mmol/kg. In a third model (unilateral hypoxia-ischemia), pretreatment of animals with glucose augmented the ischemic elevation of lactate from 30 mmol/kg to 40 mmol/kg and greatly impaired restoration of energy metabolites during recirculation. However, glucose pretreatment had no effect on the size of the NAD pool during ischemia or early recovery. These results, therefore, demonstrate that the pyridine nucleotide pool is not rapidly degraded during ischemic insults that accumulate high concentrations of lactic acid. The stability of the NAD pool may have been enhanced by the limited increase in brain levels of NADH that occurred in these models of incomplete ischemia.
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PMID:Effect of lactacidosis on pyridine nucleotide stability during ischemia in mouse brain. 361 29

Respiratory and phosphorylating capacities of kidney mitochondria were distinctly decreased within early (1.5 hr) and late (1 day) postischemic periods after long-term (2-3 hrs) ischemia of rat kidney. Preadministration of adenine (ADP, AMP) and pyridine (NAD) nucleotides into the animals prevented the decreases, while vitamin E, heparin, trifluoroperazine or aminazine proved to be ineffective. Depletion of mitochondrial nucleotide pool, which occurred during long-term ischemia of kidney and were maintained within the post-ischemic period, appears to be responsible for impairment of oxidative phosphorylation.
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PMID:[Changes in and pharmacological correction of oxidative phosphorylation in regional kidney ischemia]. 376 3

The relationships among isometric tension development, the oxidation-reduction states of pyridine nucleotides and cytochrome c, and the oxygenation state of myoglobin have been assessed using the arterially perfused rabbit interventricular septum under different conditions of contraction rate, perfusate [Ca2+] and pH, catecholamine stress, and hypoxia. Hypoxia was produced either by decreasing oxygen availability with maintained flow (high-flow hypoxia) or by decreasing the flow rate (ischemia). Under normoxic conditions, increased work caused a fall of the cytosolic adenine nucleotide phosphorylation potential, delta G(ATP)c, an oxidation of the pyridine nucleotides, and a reduction of cytochrome c; the opposite occurred with decreased work. Thus, the redox potential span from NADH to cytochrome c, delta Eh, varied with the energy demand such that delta Eh and delta G(ATP)c changed in the same direction. Under hypoxic conditions, all respiratory components became more reduced, and myoglobin was partially deoxygenated. The percentage change of developed tension under hypoxic conditions was approximately proportional to the percentage change of oxidized cytochrome c. When high-flow hypoxia and ischemia were compared at the same rates of oxygen delivery, the developed tension at any level of cytochrome c reduction was always lower with ischemia than with high-flow hypoxia. This difference was attributed to the low intracellular pH of ischemic tissue. Myoglobin deoxygenation was linearly related to cytochrome c reduction under all conditions of hypoxia, indicating steep oxygen gradients. The results support the concept of heterogeneous oxygenation of the tissue with mixed populations of aerobic and anaerobic mitochondria in the hypoxic state. In the full aerobic state, the control of mitochondrial respiration in situ appears similar to that of isolated mitochondria.
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PMID:Mitochondrial function in normal and hypoxic states of the myocardium. 630 29

Effect of ischemia and cytochrome c on oxidation of pyruvate and malate as well as of 3-hydroxybutyrate, succinate and exogenous NADH was studied. Respiration of mitochondria at the state 3 was markedly decreased in presence of the mixtures free of cytochrome c and containing pyruvate and malate, 3-hydroxybutyrate and succinate. In the same mixtures, but containing cytochrome c, oxidation of NAD-dependent substrates was decreased less distinctly and oxidation of succinate was similar to the control values. The rate of rhothenone-sensitive oxidation of NADH as well as the activating effect of cytochrome c on oxidation of all the substrates studied, except of NADH, were increased in ischemia. The data obtained suggest that alterations in the mitochondria functional activity in ischemia occur due to an increase in penetration of pyridine nucleotides across the inner membrane and of cytochrome c across the outer layer. Heterogeneity of mitochondria is discussed.
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PMID:[Effect of ischemia on the functional activity and membrane permeability of heart mitochondria]. 633 Oct 1

The effects of 3 hours of ischemia and 1 hour of reperfusion on biochemical, physiological and ultrastructural parameters were studied in 12 dogs. In the ischemic subendocardium without reperfusion, mitochondrial losses of adenine (ATP + ADP + AMP) and pyridine (NAD + NADH) nucleotides far exceeded those observed in whole tissue. Adenine nucleotide translocator (ANT) was severely inhibited and seemed to be a sensitive indicator of a lesion of the inner mitochondrial membrane. Postischemic reperfusion led to a slight loss of adenine and pyridine nucleotides from the reversibly damaged subepicardium and to an enormous loss from the irreversibly damaged subendocardium. The washout of nucleotides from irreversibly damaged areas caused the negative para-Nitro Blue Tetrazolium ( pNBT ) staining of the infarcted tissue. Diagnosis of cell death with pNBT failed after the occlusion period without reflow because pyridine, although lost from the mitochondria, was still present in the tissue. In reversibly injured areas, mitochondrial function and ultrastructure were restored after reperfusion, although a significant nucleotide loss was found in the tissue. These studies suggest that mitochondrial ultrastructure and function may play a key role in cellular viability during recovery from ischemia.
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PMID:Mitochondrial damage during myocardial ischemia. 674 90

Sixty-three mongrel dogs were exposed to 8-10 min. of complete cerebral ischemia with Aortic occlusion balloon catheter and followed by 120 min. of recirculation. The degree and distribution of post-ischemic reperfusion in 11 different cerebral regions were then assessed using radioactive labelled microspheres (15 +/- 3 micrometers). The animals were divided into 3 groups by the administration of drugs as follows: 1) no additional drugs; 2) Indomethacin (selective inhibitor of cyclooxygenase) 4 mg/kg 5 min. after ischemia; 3) Pyridine deriv. (OKY-1580 Na-salt, selective inhibitor of thromboxane synthetase) infusion 100 gamma/kg/min. beginning 5 min. after ischemia. Animals receiving no additional drugs had low cerebral blood flow rates at 120 min. after ischemia especially in basal ganglia and cerebral cortex. Animals receiving Indomethacin did not differ significantly from the no additional drug group. The significant enhancement and redistribution of post-ischemic reperfusion at 120 min. after ischemia occurred in animals receiving Pyridine deriv. with reversal of the state of poor reperfusion. These observations implicate an imbalance of prostaglandin pathways in platelets and blood vessel walls in the genesis of impaired post-ischemic reflow and suggest the usefulness of Pyridine deriv. in the treatment of local vasoconstriction of the brain after total cerebral ischemia.
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PMID:[Cerebral blood flow after total cerebral ischemia in dog (author's transl)]. 733 24


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