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

Restoration of blood flow after 15 or 45 min. of ischemia induced an immediate recovery of phosphocreatine level and adenylate energy charge whereas ATP and total adenine nucleotides remained significantly below their normal values. These results prove that oxidative phosphorylations are not impaired but that a pool of myocardial adenine nucleotides is lost during ischemia which cannot be restored shortly after reperfusion. The significance of energy charge as a regulatory parameter in the myocardium is discussed.
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PMID:[Biochemical effects of reperfusion after regional myocardial ischemia of different duration in the open chest dog]. 11 59

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

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

The levels of the adenine nucleotides ATP, ADP, and AMP in the stria vascularis were measured under normal conditions, and following various durations of ischemia. The concentrations of these compounds were used for the calculation of the adenylate energy charge, the energy status and the phosphorylation state of the stria. Following 10 min of ischemia the adenylate energy charge had decreased three fold, the energy status seven fold and the phosphorylation state 14 fold. To study the potential for recovery of strial function following various brief and prolonged ischemic intervals, a method for the perfusion of the ear via the anterior inferior cerebellar artery was developed. For various reasons it was found advantageous to use "artifical blood" as perfusate, relying upon fluorocarbons as oxygen carriers. The endolymphatic potential was used as electrical indicator of strial function. Recovery of the endolymphatic potential following brief periods of ischemia was paralleled by a corresponding increase of the ATP levels and a drastic decrease of the AMP levels of the stria vascularis. Preliminary results on the effects of substrate-free perfusion are presented.
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PMID:Adenine nucleotides of the stria vascularis. 48 54

The relationship between oxygen deficiency-reduced high energy phosphate levels and their resynthesis upon return to aerobic conditions was investigated in the isolated perfused rat heart. Any net adenosine triphosphate (ATP) hydrolysis during anoxia tended to impair ATP resynthesis with subsequent aerobic perfusion. Thirty minutes of ischemia reduced myocardial ATP 50%, and with restoration of aerobic conditions ATP increased to only 60% of control levels. The major source of postischemic and postanoxic ATP was adenosine 5'-monophosphate and adenosine 5'-disphosphate. Loss of purine base from oxygen-deficient cells limited restoration of ATP. The inclusion of adenosine, ATP, or creatine phosphate (CP) in the perfusate did not enhance postischemic tissue adenine-nucleotide concentrations. Postischemic and postanoxic CP concentrations returned to control values and were independent of ischemic and anoxic ATP and CP concentrations. Complete resynthesis of CP suggests that cellular energy-producing pathways were functional. Ventricular performance was directly related to tissue ATP concentration in aerobic control, postischemic, and postanoxic hearts. Thus, loss of adenine nucleotides during oxygen deficiency may impair subsequent aerobic synthesis of ATP and mechanical function.
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PMID:Myocardial ATP synthesis and mechanical function following oxygen deficiency. 64 29

The present study, which concerns the rate of changes in the cerebral cortex concentrations of phosphocreatine (PCr), ATP, ADP, AMP, lactate and pyruvate during complete ischemia, had the objective of finding out whether or not phenobarbital retards depletion of tissue energy reserves during ischemia. Ischemia was induced for periods of 10 s to 10 min in animals maintained on 70% N2O or given 150 mg.kg-1 of phenobarbital. The results showed that the barbiturate anaesthesia delayed utilization of ATP during the first 2 min. However, after 5 min of ischemia PCr and ATP concentrations, as well as the calculated adenylate energy charge, were identical in animals anaesthetized with nitrous oxide and phenobarbital. Thus, phenobarbital induces a very moderate delay in the depletion of cerebral energy reserves that occurs during complete ischemia. The results obtained after 5-20 s of ischemia allowed calculation of energy (approximately P) utilization according to Lowry et al. (1964). The closed system method gave values for approximately P utilization which were not far from those obtained by CMRo2 measurements. However, with normal values for metabolic rate (70% N2O) valid estimates are obtained only with very short ischemic periods (5-10 s) and, with such short periods, the oxygen content of the tissue may introduce an error.
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PMID:Influence of phenobarbital on changes in the metabolites of the energy reserve of the cerebral cortex following complete ischemia. 71 81

The purpose of the reported experiments was to measure the strial concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) in order to arrive at estimates of three commonly used adenylate ratios. Under normal conditions, the concentrations of ATP, ADP, and AMP were found to be 11.4, 3.7, and 0.6 mmoles/kg dry weight, respectively. Of the three substances, AMP is the most sensitive indicator of metabolic stress, since its concentration doubles within 6 sec. of ischemia and reaches a peak level of about 1500% of the control following 65 sec. of ischemia. Under normal conditions, the "adenylate energy charge," the "energy status," and the "phosphorylation state" amount to 0.84, 3.0, and 1.52 gram wet weight/mumole, respectively. In ischemia of 10 min. duration, the adenylate energy charge decreases 3 fold, the energy status 7 fold and the phosphorylation state 14 fold. The size of the adenylate pool shows a slight increase in the earliest stage of ischemia, but declines progressively thereafter. The apparent equilibrium constant of strial adenylate kinase was found to be 0.48. The advantages and limitations of the different adenylate ratios, as indicators of metabolic health and as regulatory parameters, are discussed.
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PMID:Adenylate energy charge, energy status, and phosphorylation state of stria vascularis under metabolic stress. 73 98

The effects of occlusion of the left anterior descending coronary artery on a variety of metabolic parameters was examined in both infarcted and noninfarcted areas of the dog heart. These included mitochondrial performance, glycolysis, in vitro contractility, and regional myocardial blood flow. Measurements were made at 1 and 3 h after onset of ischemia. Regional coronary blood flow was measured in infarcted, noninfarcted and borderline regions using radioactive microspheres. Blood flow through the ischemic area was reduced by an average of 69% after 1 h of ischemia, and 75% after 3 h. After 3 h the subendocardium of the borderline region also revealed a significantly reduced blood flow. Mitochondria isolated from the ischemic region of the heart exhibited a substantial decrease in the rate of respiration (QO2), and minor reductions in the coupling between oxidative phosphorylation and electron transport (RCI), and in the amount of ADP phosphorylated per oxygen reduced (ADP:O ratio). Levels of hexose monophosphates were elevated 1 and 3 h after ischemia was initiated. At the same time, the concentration of fructose-1,6-diphosphate declined markedly, reflecting inhibition of glycolysis at the phosphofructokinase level. Concentrations of the adenosine phosphate moieties, as well as creatine phosphate, were reduced, while levels of free fatty acids were elevated in ischemic tissue. The in vitro contractility of glycerinated ischemic muscle fibers was also depressed. Significant changes were found in maximal tension development (P0), maximal rate of tension development (dp/dtmax), time to peak tension (t0), and shortening velocity at zero load (Vmax).
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PMID:Regional blood flow, contractility and metabolism in early myocardial infarction. 87 51

The permissible duration of brain ischemia without sustaining damage is short. Less clear are the mechanisms accounting for the vulnerability of brain to ischemic insults. Neurochemical factors implicated include impairment of energy synthesis by mitochondria and of energy-dependent processes such as synaptic transmission, ATPase activity, membrane conductance and altered protein and lipid synthesis. To clarify the vulnerability of energy metabolism, we investigated energy availability and synthesis in our model of global cerebral ischemia. Our studies evaluated in vitro mitochondrial ATP synthesis and the in vivo quantitation of the cortical adenylate pool. Results of our investigations support a growing body of evidence showing the energy state to be relatively stable to ischemia. We conclude that an energy-dependent process of brain is primarily vulnerable to ischemia.
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PMID:Energy metabolism during brain ischemia. Stability during reversible and irreversible damage. 119 33

Modeling of ischemic phenomena in vitro has been hindered by the inability to create specific alterations in the variables of interest over a defined time-frame. In particular, changes in the adenine nucleotide pool have been quite difficult to mimic because of the putative low metabolic rate in culture and the long times necessary to achieve even partial chemical energy depletion. Here we present evidence for a rapid method of producing a profound chemical energy depletion with the combination of a NADH dehydrogenase inhibitor (amytal) and a mitochondrial proton ionophore (CCCP). Treatment with our protocol in enriched spinal cultures results in a 40% decrease in ATP within 2 min and a fall to one-third of control values by 15 min. The overall pool size of the total adenine nucleotides is decreased 46% by 15 min and does not completely recover after 5 min of reenergization. The ATP/ADP ratio declines to one-third of control values during deenergization and returns to control values after 5 min in control buffer. Such a loss of the total adenylate pool closely mimics that seen in vivo during ischemia and provides an in vitro model system in which the effects of the combination of this means of cellular injury with others (e.g., excitotoxins) may be examined.
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PMID:Energy depletion in culture. Adenine nucleotides are altered as in vivo. 177 32


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