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

Nucleotide metabolism was studied in rats during and following the induction of 10 min of forebrain ischemia (four-vessel occlusion model). Purine and pyrimidine nucleotides, nucleotides, and bases in forebrain extracts were quantitated by HPLC with an ultraviolet detector. Ischemia resulted in a severe reduction in the concentration of nucleoside triphosphates (ATP, GTP, UTP, and CTP) and an increase in the concentration of AMP, IMP, adenosine, inosine, hypoxanthine, and guanosine. During the recovery period, both the phosphocreatine level and adenylate energy charge were rapidly and completely restored to the normal range. ATP was only 78% of the control value at 180 min after ischemic reperfusion. Levels of nucleosides and bases were elevated during ischemia but decreased to values close to those of control animals following recirculation. Both the decrease in the adenine nucleotide pool and the incomplete ATP recovery were caused by insufficient reutilization of hypoxanthine via the purine salvage system. The content of cyclic AMP, which transiently accumulated during the early recirculation period, returned to the control level, paralleling the decrease of adenosine concentration, which suggested that adenylate cyclase activity during reperfusion is modulated by adenosine A2 receptors. The recovery of CTP was slow but greater than that of ATP, GTP, and UTP. The GTP/GDP ratio was higher than that of the control animals following recirculation.
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PMID:Mononucleotide metabolism in the rat brain after transient ischemia. 370 29

The effect of repetitive periods of coronary occlusion on myocardial adenine nucleotides, lactate, and infarct size was studied. In one series of dogs, the circumflex artery was occluded for one, two, or four 10-min episodes, each separated by 20 min of reperfusion. Hearts were excised and sampled for metabolic assays after one or more periods of ischemia before or after reperfusion. One 10-min period of ischemia caused a 61% loss of ATP and 41% loss of adenine nucleotides from the most severely ischemic subendocardial zone. Reperfusion resulted in rapid restoration of the adenylate charge but in only slight repletion of the adenine nucleotide pool. However, two or even four 10-min periods of ischemia caused no further adenine nucleotide loss. In contrast, 40 min of continuous coronary occlusion caused an 87% depletion of ATP and 67% of the adenine nucleotide pool from the same subendocardial region. Collateral blood flow was similar during all occlusions, but lactate accumulation was less during later occlusions. In a second series of experiments, myocardial necrosis was quantitated 4 days after four 10-min periods of ischemia. Necrosis was observed in only one of six dogs and, in this dog, was only 1.5% of the anatomic area at risk. Thus intermittent reperfusion prevents cumulative metabolic deficits and myocardial ischemic cell death, perhaps by restoring the capacity for high-energy phosphate (HEP) production and/or washing out deleterious catabolites. A first episode of ischemia also slows HEP utilization in subsequent episodes.
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PMID:Four brief periods of myocardial ischemia cause no cumulative ATP loss or necrosis. 378 83

The acute effects of reperfusion on myocardium reversibly damaged by 15 minutes of severe ischemia in vivo, were studied. Changes in the adenine nucleotide pool, cell volume regulation, myocardial calcium, and ultrastructure were studied at the end of 15 minutes of ischemia and after 0.5, 3.0, and 20 minutes of reflow. Before reperfusion, adenosine triphosphate and the adenylate pool decreased by 63% and 44% of control, respectively, and the adenylate charge was reduced to 0.65. After 3 minutes of reperfusion, the adenylate charge was restored to control by the rephosphorylation of adenosine mono- and diphosphate, but adenosine triphosphate was still reduced by 45%. Mild tissue edema was detected after 0.5 minute of reflow and persisted throughout 20 minutes of reperfusion. The increased tissue water was accompanied by a slight increase in sodium and a marked increase in tissue potassium. Although massive calcium accumulation develops when irreversibly injured tissue is reperfused, no calcium overload was detected during early reperfusion of reversibly injured myocytes. Reperfusion for 3 minutes exaggerated the mitochondrial swelling induced by 15 minutes of ischemia but after 20 minutes of reperfusion, myocardial ultrastructure was essentially normal except for rare swollen, or disrupted, mitochondria. Thus, the cellular abnormalities associated with brief periods of ischemia persist for variable periods of time after reperfusion of reversibly injured myocytes. First: although adenine nucleotide repletion occurs very slowly, the adenylate charge was restored after 3 minutes, indicating rapid resumption of mitochondrial adenosine triphosphate production. Second: calcium overload was not detected, but myocardial edema and increased potassium persisted throughout the 20 minutes of reperfusion. Third: the ultrastructural consequences of ischemia were nearly reversed after 20 minutes of reperfusion.
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PMID:Effect of reperfusion late in the phase of reversible ischemic injury. Changes in cell volume, electrolytes, metabolites, and ultrastructure. 397 4

The effect of different degrees of lactic acidosis on the recovery of brain mitochondrial function, measured as respiratory activity in isolated mitochondria or cortical concentrations of labile phosphates and carbohydrate substrates, was studied during 30 min of recirculation following 15 min of near-complete forebrain ischemia in rats. During ischemia, there was a marked decrease in mitochondrial State 3 respiration in vitro and a depletion of energy stores (i.e., phosphocreatine, ATP, glucose, and glycogen) in vivo that was similar in the high- and low-lactate ischemia groups. However, lactate concentrations differed markedly (20 and 10 mumol g-1, respectively). During recirculation, there was a near-complete recovery of both respiratory activity in vitro and adenylate energy charge (EC) in vivo regardless of the differences in lactic acidosis during ischemia. Respiratory activity and EC were well correlated. The changes in Ca2+ homeostasis during ischemia, an increase in tissue and a decrease in mitochondrial Ca2+ content, were reversed rapidly after ischemia in both high- and low-lactate ischemia animals and did not hinder an early recovery of mitochondrial function. It is concluded that lactic acidosis, with lactate levels reaching 20 mumol g-1 during 15-min ischemia, does not adversely affect early postischemic recovery of mitochondrial function.
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PMID:Lactic acidosis and recovery of mitochondrial function following forebrain ischemia in the rat. 398 25

Hearts of chicks fed the creatine analog, 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine), accumulated 15 mumol/g wet wt of the synthetic phosphagen, cyclocreatine-3-P; had total creatine levels reduced from the normal 6 mumol/g to only 1.8 mumol/g; and had their glycogen levels tripled. During total ischemia in vitro these hearts utilized the cyclocreatine-P for synthesis of ATP, had greatly prolonged glycolysis, and exhibited a two- to fivefold delay in depletion of both ATP and the total adenylate pool, relative to controls. Accumulation from the diet of comparable levels of the closely related 1-carboxyethyl-2-imino-3-phosphonoimidazolidine (homocyclocreatine-P) by heart was accompanied by only slight lowering of total creatine to 4.2 mumol/g, and a tripling of glycogen levels. During ischemia these hearts exhibited prolonged glycolysis, but they did not utilize the very stable homocyclocreatine-P (200,000-fold less reactive than creatine-P) and thus formed less Pi; most significantly, there was no delay in depletion of ATP levels relative to controls. Feeding of creatine doubled total creatine levels in heart, but had no marked effect on ATP depletion during ischemia; in all dietary groups creatine-P pools had fallen to less than or equal to 1.2 mumol/g by first tissue sampling. Although adaptive responses were also involved, maximal conservation of ATP and total adenylate pools in heart during ischemia apparently required, in addition to adequate glycogen reserves, substantial levels of a kinetically competent phosphagen that is thermodynamically poised to continue to assist glycolysis in buffering decreases and oscillations in the [ATP]/[free ADP] ratio at the lower phosphorylation potentials and more acid pH characteristic of later stages of ischemia. Decreases and oscillations in the [ATP]/[free ADP] ratio cannot be buffered effectively late in ischemia by the creatine-P system for thermodynamic reasons, or by the homocyclocreatine-P system because of kinetic limitations.
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PMID:Relative abilities of phosphagens with different thermodynamic or kinetic properties to help sustain ATP and total adenylate pools in heart during ischemia. 399 95

In this review of brain energy metabolism, the utilization of glucose as the sole energy source in the normal brain is described and presented in a schematic form. Important reactions concerned with the synthesis and degradation of the energy carrier in the cell, ATP, are also noted. Changes in energy metabolism with acute oxygen deficiency are shown in the example of rat brain energy metabolism during 30 seconds of nitrogen breathing (significant decrease of phosphocreatine, ATP, total adenine nucleotides and adenylate energy charge). Several important metabolic changes, particularly in ion and lipid metabolism during the decrease in the cerebral blood flow (ischemia), are described in some detail and presented in schematic form. A short description of the [14C]-2-deoxyglucose method developed by L. Sokoloff for the determination of local cerebral utilization of glucose is followed by a description of the application of this method in the study of aging in rats.
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PMID:[Energy metabolism in the brain]. 405 5

Calcium entry blockers can effectively preserve high-energy phosphates in ischemic heart. However, little is known about the optimal timing of drug therapy. The moment of nisoldipine administration in relation to its protective efficacy during ischemia and reperfusion was studied in rat hearts. Nisoldipine (50 nM), given some time before a reduction of about 90% in coronary flow diminished ATP-catabolite efflux during both ischemia and reperfusion by up to 85%. In contrast, drug administration at the onset of ischemia, or during ischemia or during reperfusion was completely without protective effect. Similarly, early nisoldipine application gave rise to ischemic ATP, adenylate charge and creatine phosphate values higher than those in untreated or late-treated hearts. Nisoldipine decreased the tension developed before ischemia by up to 66%, without affecting (post)ischemic function. Nisoldipine spares energy effectively only if administered to the heart prior to ischemia. This presumably has to do with its negative inotropy before flow reduction.
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PMID:Timely administration of nisoldipine essential for prevention of myocardial ATP catabolism. 408 50

Hypoxia is commonly invoked to explain alterations in mental function, particularly in patients with cardiac pulmonary failure. The effects of acute graded hypoxia or higher integrative functions are well documented experimentally in man. Hypoxia in experimental animal models demonstrates that the pathophysiology is complex. In mild to moderate hypoxia, in contrast to severe hypoxia and to ischemia, the supply of energy for the brain is not impaired; cerebral levels of adenosine triphosphate (ATP) and adenylate energy charge are normal. In contrast, the turnover of several neurotransmitters is altered by mild hypoxia. For example, acetylcholine synthesis is reduced proportionally to the reduction in carbohydrate oxidation. This relationship holds in vitro and with several in vivo models of hypoxia. Pharmacologic and physiologic studies in man and experimental animals are consistent with acetylcholine having an important role in mediating the cerebral effects of mild hypoxia. These observations raise the possibility that treatments directed to cholinergic or other central neurotransmitter systems may benefit patients with cerebral syndromes secondary to chronic hypoxia.
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PMID:Brain dysfunction in mild to moderate hypoxia. 611 79

The effects on central hemodynamics and skeletal muscle metabolism during surgery for abdominal aortic aneurysm were compared in 6 patients given a preoperative adrenergic block (group B) and in 6 patients who additionally had a temporary brachio-femoro-femoral by-pass during the aortic clamping (group B + S). The cardiac output, heart rate, arterial and pulmonary artery pressures and the cardiac filling pressure were studied. Biopsy specimens from the lateral vastus muscle and blood samples from the radial artery and the iliac vein were taken before aortic clamping and also before and 30 minutes, 4 and 16 hours after the aortic declamping. Intramuscular temperature and pH were measured. The glycogen, glucose, lactate, pyruvate, ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) contents of the muscle and the lactate and pyruvate concentration in iliac venous and radial arterial blood were determined, using enzymatic fluorometric techniques. In group B, aortic clamping induced severe temporary incomplete ischemia with a 300% increase in lactate/pyruvate (L/P) ratio and a fall in intramuscular pH (pHm). The adenylate energy charge (EC) decreased, but the creatine (PCr + CR) and the adenylate (ATP + ADP + AMP) pool remained unchanged. After aortic declamping, the L/P ratio, EC and pHm regained their preclamping values, but the pools of energy phosphate compounds were reduced, indicating dysfunction or damage of the muscle cells. In group B + S there were no major muscle metabolic changes during clamping or after declamping of the aorta. In group B the systemic vascular resistance (SVR), mean arterial blood pressure (MAP) and left ventricular stroke work (LVSW) increased during the occlusion. On release of the clamp, cardiac output rose, possibly due to the sudden reduction of SVR. A temporary marked fall of MAP occurred. In group B + S, no increase of SVR, MAP or LVSW was observed during aortic clamping. After the declamping, only a minor MAP drop was observed. In both groups, a brief rise in pulmonary vascular resistance after the aortic declamping suggested transient pulmonary microembolism. If a high-risk patient is to undergo reconstructive surgery of the abdominal aorta and/or technical difficulties can be expected to necessitate prolonged cross-clamping during the operation, a temporary extracorporeal by-pass may be a favorable adjuvant, improving cardiac performance and preventing derangement of muscle metabolism.
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PMID:Temporary incomplete ischemia of the legs induced by aortic clamping in man. Metabolic and hemodynamic effects of temporary extracorporeal by-pass. 613 73

Moderate unilateral cerebral ischemia was produced by microembolism in 24 adult cats. Two million plastic microspheres with a diameter of 15 +/- 5 microns were injected into the left common carotid artery via the lingual artery. The physiological and metabolic responses to embolism were accessed by electrocorticography and by determining the cerebral energy state. Embolism caused an immediate slowing and voltage reduction of the ipsilateral electrocorticogram with a gradual recovery after 30 to 60 min. Some animals also had an immediate and short depression of the contralateral electrocorticogram. In spite of the market functional suppression, metabolites of the cerebral energy-producing metabolism in most of the animals changed only slightly. In the embolized hemisphere pyruvate increased from 0.06 to 0.10 mumol/g and lactate from 1.9 to 4.6 mumol/g within 5 min after embolization and remained at this level during the 4 h observation period. Phosphocreatine, adenosine triphosphate and the energy charge of the adenylate pool remained uncharged during this period. However, there was a slight increase of ATP in the non-embolized hemisphere during the early postembolic period. In two animals, the initial slowing of the electrocorticogram recurred and spread to the contralateral hemisphere, followed by bilateral flattening after a few hours. This delayed functional deterioration was accomplished by complete loss of energy-rich phosphates. These animals also had a progressive increase of cerebrospinal fluid (CSF) pressure and considerable brain swelling with cerebellar herniation after 4 h. It is concluded that unilateral cerebral embolism in the above concentration leads only to a slight increase of anerobic glycolysis without significant perturbation of the cerebral energy state, unless progressive brain swelling with cerebrellat herniation supervenes. This supports previous findings, that brain edema and not initial ischemia is the main pathogenetic factor for tissue damage in cerebral microembolism.
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PMID:The effect of mild microembolic injury on the energy metabolism of the cat brain. 615 90


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