Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new approach for the evaluation of brain energy metabolism in awake animals became possible as UV transmitting optical fibers became available. A variety of surface fiber optic fluorometers / reflectometers which were developed during the past decade enabled the monitoring of intramitochondrial NADH redox state in unanesthetized animals. The bundle of flexible fibers was connected to the brain via a cemented light guide holder implanted epidurally. The two signals obtained, 366 nm reflectance and 450 nm fluorescence, are subjected to various artifacts not connected to the intramitochondrial NADH redox state. In our system, the effects of movement artifacts and changes in blood oxygenation are negligible while the effects of tissue absorption or blood volume changes are considerable and could be minimized by subtraction of the two signals (1:1 ratio) providing the corrected fluorescence signal. The brain was exposed to various physiological and pathological conditions which resulted in the increase or decrease in the level of NADH. Under anoxia, hypoxia and ischemia, oxygen availability decreased and the metabolic state of the brain became more reduced (state 4-5 transition). When the brain was activated by seizures, spreading depression of hyperbaric oxygenation NADH became more oxidized (state 4-3 transition).
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PMID:Brain NADH redox state monitored in vivo by fiber optic surface fluorometry. 637 Mar 76

Direct recording of reduced nicotinamide adenine dinucleotide (NADH) fluorescence was conducted with an organ redoximeter in isolated perfused guinea pig heart. Cross-clamping of the aortic inflow line resulted in an increase in NADH fluorescence. After etafenone (10(-6) M), there was a significant prolongation of the time to the detectable or the maximum increase in NADH fluorescence. The magnitude of the increase in NADH fluorescence tended to be reduced (135% as compared with 145% in the control group). Supplemental chemical analyses revealed a significant increase in creatine phosphate, adenosine triphosphate (ATP) and total adenine nucleotide in the etafenone-pretreated group 15 min after postischemic reperfusion, although the ischemia-induced changes were not improved by this compound. It was suggested that the better recovery of myocardial high energy phosphate levels produced by etafenone was brought about by a decrease in oxygen consumption due to a decrease in mechanical performance of the heart and possibly by a better resynthesis of ATP.
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PMID:Effects of etafenone on myocardial energy metabolism as studied by an organ redoximeter and biochemical analyses. 648 88

The mechanism of irreversible damage to ischemic myocardium was investigated in the perfused rat heart. The time of transition from reversible to irreversible damage to contractile function was accelerated by accumulation of glycolytic products and increases in extracellular calcium. Both of these effects were largely independent of adenine nucleotide levels in the tissue. With zero coronary flow and 1.25 mM calcium the decrease in ability of the heart to recover ventricular function with reperfusion after 30 minutes of ischemia was directly correlated with accumulation of glycolytic products (as estimated by tissue lactate) during ischemia. The extent of lactate accumulation during ischemia was varied by preperfusing the hearts for 0, 10, or 15 minutes under anoxic, high coronary flow conditions to deplete tissue glycogen prior to ischemia, and by adding lactate back to the perfusate of these hearts during the ischemic period. Recovery of ventricular function was inversely related to tissue lactate during ischemia and varied from 28 to 92%, even though there was little or no change in tissue levels of residual adenosine triphosphate. Increasing extracellular calcium accelerated the time of onset of irreversible damage with little or no change in residual adenosine triphosphate levels. At any given calcium concentration, the time-dependent declines in the ability of the heart to recover ventricular function was also largely independent of adenosine triphosphate levels. These studies suggest a major role of anaerobic glycolytic products (lactate, hydrogen ion, or NADH) in ischemic damage to the heart that is unrelated to loss of tissue adenine nucleotides. With zero or low flow ischemia, this effect may result in irreversible damage to the myocardium before adenine nucleotides are reduced to critically low levels.
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PMID:Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts. 649 36

The interrelation between the metabolic responses to ischemia and seizure propensity was studied in two groups of seizure prone (SP) and non-seizure prone (NSP) gerbils. The metabolic state was evaluated in vivo using the light guide surface fluorometry as well as in the frozen brain scanned at liquid N2 temperature for Fp/PN ratio after monitoring the brain in vivo. The results could be summarized as follows. (1) Unilateral carotid artery occlusion led to partial ischemia in the ipsilateral hemisphere while the contralateral hemisphere remained normoxic. (2) Animal variability in the degree of the ischemia insult due to unilateral occlusion was not side dependent or in correlation with seizure propensity. (3) Significant correlation was found between the NADH increase during ischemia and the redox state measurements done in the same brain after funnel freezing with liquid nitrogen. (4) In a large number of the gerbils (not depending on the origin or strain) a peculiar inter-hemispheric blood supply connection was found. A narrow band (1 mm in width) of tissue near the midline obtained its blood via the same vessels supplying the contralateral hemisphere. (5) We did not find any correlation between blood vessel anatomy to the brain and seizure propensity.
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PMID:Brain metabolic responses to ischemia in the mongolian gerbil: in vivo and freeze trapped redox scanning. 662 5

In Langendorff-perfused guinea pig hearts, local myocardial perfusion was evaluated by analysis of FITC-dextran-150 elution kinetics after bolus injection. Locally estimated half-times of the monoexponential elution curves showed good correlation with global undisturbed coronary flow. After ligation of the left anterior descending coronary artery indicator transit kinetics in the ischemic area were only slightly affected (increase of t/2 by 30 +/- 19%), indicating a residual flow of 80% to the ligated area. The moderate increase (40 +/- 20%) of NADH-surface fluorescence in the same area confirms a high degree of residual flow. Indicator partition volume (signal peak height after bolus injections) was additionally enhanced. Moreover, indicator transit kinetics changed from monoexponential to composed kinetics. On reperfusion these effects were partially reversible. Ligation of the left coronary artery at its aortic root produced only moderate ischemia, indicating very effective mechanisms in the isolated guinea pig heart from the right coronary artery to support the left ventricle. Severe ischemia as evidenced from NADH-surface fluorescence could be observed only after "stopped flow" ischemia.
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PMID:Local myocardial perfusion and epicardial NADH-fluorescence after coronary artery ligation in the isolated guinea pig heart. 673 20

Ischemic change of cerebral energy metabolism and catecholamine have already been discussed largely using biochemical quantitative assay. However, regional change and their correlation are not well understood. In the present study, the ischemic regional change of cerebral energy metabolism and catecholamine were investigated in gerbils and histochemical method. Adult either sex mongolian gerbils, weighing 50-100 g, were anesthetized with ether and the left carotid artery was ligated. After observation of clinical symptoms, the brain was frozen in situ by pouring liquid N2 after 30 min and 60 min of ischemic insult. The frozen brain was sectioned with precooled saw in the coronal plane. The brain section were placed in liquid N2 bath and illuminated with 366 nm light (UV) from a 200 watt mercury lamp and Corning filter 5840. NADH fluorescence was recorded photographically through Corning filter 3387 and 5562. Also UV reflectance was recorded through Corning filter 5840 to observe quenching effect of hemoglobin. Regional change of catecholamine was observed in the same frozen brain processed with Falck-Hillarp method. According to neurological abnormalities following left carotid ligation, animals were divided into three groups; symptomatic, borderline and asymptomatic. The intensity and distribution of tissue NADH fluorescence were closely correlated to the clinical symptoms. In the symptomatic group, both in 30 min and 60 min of ischemia, homogeneously and markedly increased fluorescence was observed in the ipsilateral temporal cortex, caudate nucleus, hypothalamus and dorsolateral thalamus. Columnar mild increase of NADH fluorescence was seen in the ipsilateral parietal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Regional change of brain energy metabolism and catecholamine in the early stage of experimental cerebral ischemia--histochemical study]. 673 86

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

Regional changes of cerebral blood flow and biochemical substrates were assessed in the gerbil brain following different grades of cerebral ischemia. Ischemia was produced by occlusion of the right common carotid and left external carotid arteries. Gerbils were classified according to the severity of neurological symptoms as animals without, with mild and with severe neurological deficits. Brains were frozen in situ, sliced in 20-microns sections and processed for pictorial presentation of glucose and ATP, using bioluminescence techniques. Cerebral blood flow was determined in adjacent brain sections, using [14C]iodoantipyrine autoradiography. NADH fluorescence was recorded by illuminating the surface of the tissue block with ultraviolet light. Most animals without visible neurological symptoms exhibited reduced blood flow in circumscribed regions of cortex and basal ganglia of the right hemisphere without concomitant changes of biochemical substrates. In animals with mild neurological symptoms, blood flow in the right hemisphere was reduced, glucose and ATP decreased, and NADH fluorescence unhomogeneously enhanced. In animals with severe neurological symptoms blood flow was almost arrested in the right hemisphere and was distinctly reduced in the medial parts of the left hemisphere. The ischemic tissue was depleted from glucose and ATP, and exhibited bright NADH fluorescence. The severity of neurological symptoms, in consequence, correlated closely with both the degree and the size of biochemical lesions observed in the ischemic territory.
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PMID:Biochemical changes during graded brain ischemia in gerbils. Part 2. Regional evaluation of cerebral blood flow and brain metabolites. 684 58

The maximal rate of some cerebral enzymatic activities related to energy transduction (hexokinase; phosphofructokinase; lactate dehydrogenase; citrate synthase; malate dehydrogenase; total NADH-cytochrome c reductase; cytochrome oxidase), amino acid metabolism (glutamate decarboxylase; glutamate dehydrogenase) and cholinergic metabolism (acetylcholine esterase) were tested in the cerebral cortex and in sub-cortical area of rats. The evaluations were performed both in the homogenate in toto and in the crude mitochondrial fraction, before and after a postdecapitative normothermic ischemia of 5, 10, 20, and 40 min duration. The results are discussed also with respect to the pharmacological pretreatment with two biological substances which may modulate amino acid (L-alanine) and phospholipid metabolism (CDP-choline). The analysis of the present data suggests the occurrence in brain tissue of a variety of interrelated factors implicated in the ischemia-induced changes of the maximal rate of the enzymatic activities related to the energy transduction. These include: (a) rearrangement of the enzymatic activities because of the changed metabolic and chemico-physical condition; (b) decrease in the activity of enzymes related to the electron transfer chain and glycolysis; (c) changes in enzymes related to mitochondrial membranes. The effects of in vivo administration of alanine or CDP-choline, even if significant, are not consistent throughout the time period studied.
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PMID:Changes induced by ischemia on some cerebral enzymatic activities related to energy transduction and amino acid metabolism. 685 30

The temporal relationships among onset of cellular anoxia after coronary artery occlusion, contractile dysfunction, and electrocardiographic ischemia were studied in dogs with an intact circulation. Nicotinamide adenine dinucleotide (NADH) fluorescence was used to detect intracellular anoxia, using a fiber-optic method. Paired NADH concentrations from ischemic (394 +/- 10 mumol/g) and normoxic (285 +/- 11 mumol/g) regions of the heart were obtained, and the differences (delta[NADH]) were correlated with compensated fluorescence (r = 0.76, P less than 0.01). Onset of fluorescence occurred 1 to 2 sec after coronary artery occlusion, followed by hemodynamic (5 sec) and electrocardiographic (13 sec) changes. These data indicate that intracellular anoxia, with alterations in redox potential, is not synchronous with the onset of contractile failure and provide indirect support for intracellular acidosis as the likely mediator of contractile failure.
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PMID:Detection of intracellular anoxia and its relationship to onset of hemodynamic dysfunction and ST-segment elevation in the intact dog heart. 685 70


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