UMLS:C0022116 - FACTA Search

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

Prior transient episodes of ischemia ("ischemic preconditioning") reduce lactate accumulation and attenuate acidosis during a subsequent prolonged ischemic insult. The mechanisms responsible for attenuated glycolytic catabolite accumulation have not been established but may include earlier exhaustion of glycogen stores, slowed glycogenolysis before complete glycogen depletion, and/or inhibition of glycolysis. Simultaneous repeated measures of myocardial glycogen and the rates of glycolysis, glycogenolysis, glucose utilization, and glycolytic ATP production were obtained during total ischemia by 13C nuclear magnetic resonance spectroscopy in control and ischemia-preconditioned isolated rat hearts. Both [13C]glycolytic and [13C]glycogenolytic rates were significantly lower during total ischemia in preconditioned compared with control hearts (0.77 +/- 0.04 versus 1.06 +/- 0.06 mumol/min per gram wet weight [P < .01] for glycolysis and 0.15 +/- 0.07 versus 0.78 +/- 0.12 mumol/ min per gram wet weight [P < .001] for glycogenolysis, respectively, at 2.5 minutes of ischemia). Slowed glycolysis was present even during the early minutes of ischemia, when significant amounts of available [13C]glycogen were still present. Importantly, the reduction in the rate of glycogenolysis was larger and out of proportion to the reduction in glycolysis and occurred despite an increase in glucose utilization in preconditioned hearts (2.23 +/- 0.15 versus 1.5 +/- 0.10 mumol/min per gram wet weight at 1.25 minutes, P < .01). During early ischemia, conversion of glycogen phosphorylase to the a or "active" form was less in preconditioned than in control hearts (29.1 +/- 2.6% versus 41.2 +/- 9.8%, respectively; P < .05). Taken together, these findings demonstrate that ischemic preconditioning significantly depresses glycolytic catabolite accumulation during sustained ischemia not by more severe glycolytic inhibition or exhaustion of glycogen stores but by depressed glycogenolysis from the onset of ischemia.
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PMID:Attenuated glycogenolysis reduces glycolytic catabolite accumulation during ischemia in preconditioned rat hearts. 878 77

This review deals with glycogen phosphorylase (GP) and its isoenzyme BB in the diagnosis of ischaemic myocardial injury. Early identification and confirmation of acute myocardial infarction is essential for correct patient care and disposition decision in the emergency department. In this respect, glycogen phosphorylase isoenzyme BB (GPBB) based on its metabolic function is an enzyme for early laboratory detection of ischaemia. In the aerobic heart muscle GPBB together with glycogen is tightly associated with the vesicles of the sarcoplasmic reticulum. Release of GPBB, the main isoform in the human myocardium, essentially depends on the degradation of glycogen, which is catalyzed by GP. Ischaemia is known to favour the conversion of bound GP in the b form into GP a, thereby accelerating glycogen breakdown, which is the ultimate prerequisite for getting GP into a soluble form being able to move freely in the cytosol. The efflux of GPBB into the extracellular fluid follows if ischaemia-induced structural alterations in the cell membrane become manifest. The clinical application of GPBB as a marker of ischaemic myocardial injury is a very promising tool for extending our knowledge of the severity of myocardial ischaemic events in the various coronary syndromes. The rational roots of this development were originated from Albert Wollenberger's research work on the biochemistry of cardiac ischaemia and the transient acceleration of glycogenolysis mainly brought about by GP activation.
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PMID:Glycogen phosphorylase isoenzyme BB in diagnosis of myocardial ischaemic injury and infarction. 890 85

The role played by glycogenolysis in the ischemic heart has been recently put into question because it is suspected that a slowing down of this process could be beneficial for the tolerance of the myocardium to ischemia. The role of the intracellular effectors that control the rate of glycogenolysis has therefore regained interest. We aimed to understand the role played by those intracellular effectors which are directly related to the energy balance of the heart. To this end, we review some of the previously published data on this subject and we present new data obtained from P-31 and C-13 NMR spectroscopic measurement on isolated rat heart. Two conditions of ischemia were studied: 15 min global no-flow and 25 min low-flow ischemia. The hearts were isolated either from control animals or from rats pre-treated with isoproterenol (5 mg.kg-1 b.w. i.p.) 1 h before the perfusion in order to C-13 label glycogen stores. Our main results are as follows: (1) the biochemically determined glycogenolysis rate during the early phase of ischemia (up to 10-15 min) was larger in no-flow ischemia than in low-flow conditions for both groups, (2) direct measurement of the glycogenolysis rate, as determined by C-13 NMR, after labelling of the glycogen pool in the hearts from isoproterenol-treated rats, confirms the estimations from the biochemical data, (3) glycogenolysis was slower in the hearts from pre-treated animals than in control hearts for both conditions of ischemia, (4) the total activity of glycogen phosphorylase (a + b) increased, by 50%, after 5 min no-flow ischemia, whereas it decreased by 42% after the same time of low-flow ischemia. However, the ratio phosphorylase a/a + b was not altered, whatever the conditions, (5) the concentration of inorganic phosphate (Pi) increased sharply during the first minutes of ischemia, to values above 8-10 mM, under all conditions studied. The rate of increase was larger during no-flow ischemia than during low-flow ischemia. The concentration of Pi was thereafter higher in controls than in the hearts from isoproterenol-treated animals. The calculated cytosolic concentration of free 5'AMP increased sharply at the onset on ischemia, reaching in a few minutes values above 30 microM in controls and significantly lower values around 15 microM, in the hearts from isoproterenol-treated rats. (6) The hearts from isoproterenol-treated rats displayed a reduced intracellular acidosis, when compared to controls, under both conditions of ischemia. We conclude that the intracellular effectors, mainly free AMP, play an essential role in the control of glycogenolysis via allosteric control of phosphorylase b activity. The alteration in the concentration of free Pi, the substrate of both forms of phosphorylase, can be considered as determinant in the control of the rate of glycogenolysis. The attenuation of ischemia-induced intracellular acidosis in the hearts from isoproterenol-treated rats could be a consequence of a reduced glycogenolytic rate and is likely to be related to a better resumption of the mechanical function on reperfusion.
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PMID:Crucial role of intracellular effectors on glycogenolysis in the isolated rat heart: potential consequences on the myocardial tolerance to ischemia. 890 83

The primary objective of this study was to attempt to induce excessive intraglial acidosis during ischemia by subjecting rats to an initial insult which leads to post insult accumulation of glycogen, presumed to accumulate primarily in astrocytes. The initial insults were 15 min of transient forebrain ischemia, 30 min of hypoglycemic coma, and intraperitonial injection of methionine-sulphoximine (MSO). In the first two of these insults, glycogen content in neocortex increased to 6-7 mM kg(-1) after 6 h of recovery, and in MSO-treated animals even higher values were measured 24 h after administration ( 12 mM kg(-1)). In spite of this glycogen loading, the amount of lactate formed during a subsequent ischemic insult (of 5-30 min duration) did not exceed values usually obtained during complete ischemia in animals with normal glycogen contents (tissue lactate contents of 15 mM kg(-1)) This was because appreciable amounts of glycogen (3-7 mM kg(-1)) remained undegraded even after 30 min of ischemia. The undigested part largely reflected the extra amount of glycogen accumulated after the initial insults. It is discussed whether this part is unavailable to degradation by phosphorylase.
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PMID:Glycogen accumulated in the brain following insults is not degraded during a subsequent period of ischemia. 912 Apr 90

To study the cellular events surrounding the formation of purines in cardiac ischemia, we have micromachined a micrometer-scale titer chamber containing an integrated electrochemical sensor, capable of measuring analytes produced by a single heart cell. The analytical procedure involves the determination of metabolites via the amperometric detection of enzymically generated hydrogen peroxide, measured at a platinized microelectrode, poised at a suitably oxidizing potential, equivalent to +420 mV vs Ag/AgCl. Signals were recorded as current-time responses and were integrated to give a total charge (Q) attributable to the reaction under investigation. The amount of analyte produced by the cell was subsequently quantified by the addition of a known amount of calibrant. As a consequence, by using a cascade of three enzymes (adenosine deaminase, nucleotide phosphorylase, and xanthine oxidase), we were able to show that, after rigor contracture had been induced in a single myocyte, adenosine (but not inosine) only reached the extracellular space after the cell membrane had been permeabilized by detergent. These data, which could only be obtained unambiguously by using this single-cell methodology, have provided us with information on the origin of ischemic adenosine which challenges the established assumption that purine release is an early retaliatory response from intact anoxic myocytes.
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PMID:Single-cell measurements of purine release using a micromachined electroanalytical sensor. 953 6

Muscle acidosis has been implicated as a major determinant of reflex sympathetic activation during exercise. To test this hypothesis we studied sympathetic exercise responses in metabolic myopathies in which muscle acidosis is impaired or augmented during exercise. As an index of reflex sympathetic activation to muscle, microneurographic measurements of muscle sympathetic nerve activity (MSNA) were obtained from the peroneal nerve. MSNA was measured during static handgrip exercise at 30% of maximal voluntary contraction force to exhaustion in patients in whom exercise-induced muscle acidosis is absent (seven myophosphorylase deficient patients; MD [McArdle's disease], and one patient with muscle phosphofructokinase deficiency [PFKD]), augmented (one patient with mitochondrial myopathy [MM]), or normal (five healthy controls). Muscle pH was monitored by 31P-magnetic resonance spectroscopy during handgrip exercise in the five control subjects, four MD patients, and the MM and PFKD patients. With handgrip to exhaustion, the increase in MSNA over baseline (bursts per minute [bpm] and total activity [%]) was not impaired in patients with MD (17+/-2 bpm, 124+/-42%) or PFKD (65 bpm, 307%), and was not enhanced in the MM patient (24 bpm, 131%) compared with controls (17+/-4 bpm, 115+/-17%). Post-handgrip ischemia studied in one McArdle patient, caused sustained elevation of MSNA above basal suggesting a chemoreflex activation of MSNA. Handgrip exercise elicited an enhanced drop in muscle pH of 0.51 U in the MM patient compared with the decrease in controls of 0.13+/-0.02 U. In contrast, muscle pH increased with exercise in MD by 0.12+/-0.05 U and in PFKD by 0.01 U. In conclusion, patients with glycogenolytic, glycolytic, and oxidative phosphorylation defects show normal muscle sympathetic nerve responses to static exercise. These findings indicate that muscle acidosis is not a prerequisite for sympathetic activation in exercise.
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PMID:Sympathetic activation in exercise is not dependent on muscle acidosis. Direct evidence from studies in metabolic myopathies. 954 95

The acute coronary syndromes represent a continuum of myocardial ischemia ranging from angina, reversible tissue injury --> unstable angina, frequently associated with minor myocardial damage --> myocardial infarction and extensive tissue necrosis. Historically, coronary artery disease assessment has been mainly binary, using WHO criteria of symptoms, electrocardiography, and biochemical markers. The creatine kinase-MB isoenzyme (CK-MB) has been a benchmark for markers, but it is not specific for myocardium. Cardiac-specific isoforms of troponin T and I have emerged as sensitive myocardial infarction (MI) indicators and, importantly, for risk stratification of acute coronary syndrome patients. In addition to markers of myocardial cell necrosis, markers of plaque disruption (C-reactive protein and serum amyloid A), "angry" platelets (P-selectin), ischemia (glycogen phosphorylase-BB isoenzyme), and the procoagulant state and thrombosis (soluble fibrin) have potential use. Also, CK-MB and myoglobin have been combined with clinical indicators for monitoring reperfusion after thrombolytic therapy. Biochemical markers will continue to be an important clinical adjunct for MI diagnosis, risk assessment, and reperfusion monitoring in the future.
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PMID:Biochemical markers of the acute coronary syndromes. 970 95

An in vitro model of ischemia was obtained by subjecting PC12 cells differentiated with nerve growth factor to a combination of glucose deprivation plus anoxia. Immediately after the ischemic period, the protein synthesis rate was significantly inhibited (80%) and western blots of cell extracts revealed a significant accumulation of phosphorylated eukaryotic initiation factor 2, alpha subunit, eIF2(alphaP) (42%). Upon recovery, eIF2(alphaP) levels returned to control values after 30 min, whereas protein synthesis was still partially inhibited (33%) and reached almost control values within 2 h. The activities of the mammalian eIF2alpha kinases, double-stranded RNA-activated protein kinase, mammalian GCN2 homologue, and endoplasmic reticulum-resident kinase, were determined. None of the eIF2alpha kinases studied showed increased activity in ischemic cells as compared with controls. Exposure of cells to cell-permeable inhibitors of protein phosphatases 1 and 2A, calyculin A or tautomycin, induced dose- and time-dependent accumulation of eIF2(alphaP), mimicking an ischemic effect. Protein phosphatase activity, as measured with [(32)P]phosphorylase a as a substrate, diminished during ischemia and returned to control levels upon 30-min recovery. In addition, the rate of eIF2(alphaP) dephosphorylation was significantly lower in ischemic cells, paralleling both the greatest translational inhibition and the highest eIF2(alphaP) levels. The endogenous phosphatase activity from control and ischemic extracts showed different sensitivity to inhibitor 2 and fostriecin in in vitro assays, inhibitor-2 effect in ischemic cells being lower than in control cells. Together these results indicate that an eIF2alpha phosphatase, probably protein phosphatase 1, is implicated in the ischemia-induced eIF2(alphaP) accumulation in PC12 cells.
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PMID:Ischemia-induced phosphorylation of initiation factor 2 in differentiated PC12 cells: role for initiation factor 2 phosphatase. 1108 Jan 85

N-methyl-1-deoxynojirimycin (NMDN), an a-glucosidase inhibitor, reduces myocardial infarct size by reducing the glycogenolytic rate through inhibition of the alpha-1,6-glucosidase of glycogen-debranching enzyme in the heart, in addition to possessing an antihyperglycemic action by blocking alpha-1,4-glucosidase in the intestine. Ischemic preconditioning (PC), which markedly reduces the size of the myocardial infarct, is known to reduce the activity of phosphorylase and reduce the glycogenolytic rate. Therefore, it was hypothesized that a combination of pharmacological inhibition of glycogenolysis by an alpha-1,6-glucosidase inhibitor, NMDN, and PC could markedly reduce myocardial infarct size more than NMDN or PC alone. Japanese white rabbits without collateral circulation were subjected to a 30-min coronary occlusion followed by 48-h reperfusion. The infarct sizes as a percentage of area at risk were significantly reduced by pre-ischemic treatment with either 100mg/kg of NMDN or PC of 5 min ischemia and 5 min reperfusion alone (15.9+/-2.0%, n=8, and 10.3+/-1.2%, n=8, respectively) as compared with the control (43.9+/-2.2%, n=8). However, the combination of 100mg/kg of NMDN and PC significantly reduced the infarct size (4.9+/-1.2, n=8) compared with NMDN or PC alone. Another 40 rabbits, also given 100mg of NMDN, PC, NMDN+PC or saline before ischemia (n=10 in each group), were killed for biochemical analysis after 30 min of ischemia. NMDN and PC preserved the glycogen content and attenuated the lactate accumulation, respectively, as compared with the control. However, the combination of NMDN and PC preserved significantly more glycogen and significantly reduced lactate accumulation than either NMDN or PC alone. The combination of NMDN and PC markedly reduced the myocardial infarct size more than either process alone. The marked preservation of glycogen and marked attenuation of lactate accumulation by the combination of NMDN and PC suggest that the mechanism for this effect of NMDN+PC is related to the inhibition of glycogenolysis.
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PMID:Combination of N-methyl-1-deoxynojirimycin and ischemic preconditioning markedly reduces the size of myocardial infarcts in rabbits. 1144 4

Metabolism, monitored via in situ catalytic enzyme histochemistry and fine structure, was studied in the myocardium of chronic diabetic male Wistar rats administered L-arginine (12.8 mg/100 g/day) for 24 weeks. Diabetes was induced with a single i.v. injection of 55 mg/kg streptozotocin. After 6 months, the tissue of the left ventricle was processed for electron microscope examination and transmural tissue blocks were frozen for enzyme histochemistry. In diabetic myocardium, heterogeneous ischemia-like subcellular alterations of cardiomyocytes and capillaries were observed, together with interstitial fibrosis. This structural remodeling was accompanied by significantly decreased activity of endothelial nitric oxide synthase (NOS) and heterogeneously decreased activities of glycogen phosphorylase (GlPh), hydroxybutyrate dehydrogenase (HBDH) and adenosine triphophatases (ATPases) throughout the myocardium. In arginine-treated diabetic rats, there was evidence of protected structural integrity of endothelial cells and attenuated structural disturbances of cardiomyocytes. This was associated with the markedly preserved histochemical activities of all detected enzymes in comparison with nontreated diabetic rats (NOS 98.7 +/- 10.5% vs. 35.4 +/- 4.1%; ATPases 82.7 +/- 9.1% vs. 69.3 +/- 5.2%; GlPh 65.2 +/- 8.3% vs. 45.5 +/- 3.8%; HBDH 68.9 +/- 8.5% vs. 44.1 +/- 6.7% of control values). The results indicate that long-term supplementation of L-arginine may account for the reduction of diabetes-induced myocardial structural remodeling.
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PMID:L-arginine reduces structural remodeling in the diabetic rat myocardium. 1209 6

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