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)

Pyruvate-supported oxygen uptake was determined as a measure of the functional capacity of mitochondria obtained from rat brain during unilateral middle cerebral artery occlusion and reperfusion. During ischemia, substantial reductions developed in both ADP-stimulated and uncoupled respiration in tissue from the focus of the affected area in the striatum and cortex. A similar pattern of change but with lesser reductions was seen in the adjacent perifocal tissue. Succinate-supported respiration was more affected than that with pyruvate in perifocal tissue at 2 h of ischemia, suggesting additional alterations to mitochondrial components in this tissue. Mitochondrial respiratory activity recovered fully in samples from the cortex, but not the striatum, within the first hour of reperfusion following 2 h of ischemia and remained similar to control values at 3 h of reperfusion. In contrast, impairment of the functional capacity of mitochondria from all three regions was seen in the first 3 h of reperfusion following 3 h of ischemia. Extensive infarction generally affecting the cortical focal tissue with more variable involvement of the perifocal tissue developed following 2 h of focal ischemia. Thus, mitochondrial impairment during the first 3 h of reperfusion was apparently not essential for tissue infarction to develop. Nonetheless, the observed mitochondrial changes could contribute to the damage produced by permanent focal ischemia as well as the larger infarcts produced when reperfusion was initiated following 3 h of ischemia.
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PMID:Mitochondrial respiratory function and cell death in focal cerebral ischemia. 1046 11

Pyruvate has been shown to prevent intestinal mucosal injury after ischemia-reperfusion. The aim of the present study was to determine whether pyruvate can (1) prevent postreperfusion mucosal injury occurring after intestinal preservation and subsequent transplantation and (2) exert a protective effect on the intestinal graft mucosa during acute rejection. Preservation mucosal injury was evaluated, after 2 hours of reperfusion, by comparing grafts transplanted in a rat syngeneic combination (ACI to ACI) after 2 hours of cold preservation using pyruvate (n = 6) or placebo (n = 6). Mucosal parameters obtained during acute rejection (allogeneic combination: ACI to Lewis) were compared between placebo-treated (n = 6) and pyruvate-treated (n &equals 6) animals. Tissue injury was evaluated by histopathologic examination, oxygen free radical production by luminol-enhanced chemiluminescence, and degree of neutrophil infiltration by myeloperoxidase staining. After reperfusion of the preserved grafts and during acute rejection, mucosal oxygen free radical levels and the number of infiltrating neutrophils were significantly (P <0.05) increased in the untreated grafts, whereas there was a statistically significant inhibition of these parameters in those treated with pyruvate. Mucosal injury, seen after reperfusion of the preserved grafts, was prevented by pyruvate. The histopathologic abnormalities observed in the untreated grafts during rejection were also significantly reduced by pyruvate. Treatment with pyruvate before cold preservation of intestinal grafts, in this rat model, reduced reperfusion mucosal injury, neutrophil infiltration, and oxygen free radical production. Oxygen free radicals were produced in the mucosa of the graft during acute rejection and their production was reduced by pyruvate, which exerted a protective effect on the rejecting allograft mucosa.
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PMID:Preservation injury and acute rejection of rat intestinal grafts: protection afforded by pyruvate. 1048 14

Formation of oxygen free radicals during heart transplantation seems to be related to the alterations occurring during ischemia and reperfusion and could explain the short preservation time of donor hearts. The aim of our study was (a) to analyze the protective effects of pyruvate during cold cardioplegia and ischemia/reperfusion sequence, and (b) to investigate in vitro the radical scavenging properties of this compound. After 30 min of perfusion, isolated working rat hearts were arrested by cardioplegic solution, stored 4 h in B21 solutions at 4 degrees C, and reperfused with Krebs-Henseleit buffer for 45 min. Pyruvate (2 mM) was added to Krebs-Henseleit, cardioplegic, and storage solutions, and functional parameters were recorded throughout the experiments. In a second part, control hearts and hearts treated with pyruvate were cannulated via the aorta and perfused for 30 min by the Langendorff method, arrested by cardioplegic solution, stored 4 h in B21 solutions at 4 degrees C, and reperfused for 45 min by the Langendorff method. Malonedialdehyde and alpha-tocopherol levels were determined on heart homogenate. In situ detection of apoptotic cells also was performed on tissue samples (left ventricle) at the end of the ischemia/reperfusion sequence. To demonstrate in vitro the antioxidant effects of pyruvate, we monitored (a) its hydroxyl radical scavenging properties by using electron paramagnetic resonance (EPR) spectroscopy, and (b) the decrease of fluorescence of allophycocyanin, in the presence of a Fenton system (H2O2/Cu2+). Ischemia for 4 h, followed by myocardial reperfusion, resulted in substantially reduced mechanical function. Hearts subjected to this ischemia and pretreated with pyruvate showed a significant improvement in the function recovery. After the ischemia/reperfusion protocol, no significant decrease of malonedialdehyde levels was shown on hearts treated with pyruvate. However, alpha-tocopherol levels were higher in the pyruvate group compared with the control group. At the end of the reperfusion period, levels of apoptotic cells were significantly lower in hearts treated with pyruvate compared with control hearts. EPR studies showed that pyruvate was an efficient hydroxyl scavenger, with a median inhibitory concentration (IC50) of 8 mM. The allophycocyanin assay also showed a dose-dependent effect of pyruvate against hydroxyl radicals. In conclusion, these findings showed that pyruvate could prevent reperfusion injuries in the isolated heart, probably by its antioxidative properties. The application of pyruvate may contribute to the preservation of hearts for organ transplantation.
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PMID:Antioxidative properties of pyruvate and protection of the ischemic rat heart during cardioplegia. 1054 80

Pyruvate improves cellular and organ function during hypoxia and ischemia and stabilizes the NADH redox state and cytosolic ATP phosphorylation potential. In this in vivo study, we evaluated the effects of intravenous pyruvate on cardiovascular and neocortical function, indexes of the cytosolic redox state (lactate/pyruvate ratio, L/P) and cellular energy state (adenosine and degradative products hypoxanthine and inosine, ADO + HX + Ino) during controlled arterial hemorrhage (40 mmHg) in sedated swine (45 kg). Na+ pyruvate was infused 1 h before (1 g. kg(-1). h(-1)) and 2 h during (0.5 g. kg(-1). h(-1)) hemorrhage to attain arterial pyruvate levels of 6 mM. Volume (0.9% NaCl) and osmotic (10% NaCl) effects were matched in controls. Time to peak hemorrhage (57 min) and peak hemorrhage volume (43 ml/kg) were similar in all groups. The volume and osmotic groups experienced spontaneous cardiovascular decompensation between 60 and 90 min, with an average time until death of 82.7 +/- 5.5 and 74.8 +/- 8.2 min. In contrast, survival in the pyruvate group was 151.2 +/- 10.0 min (P < 0.001). During hemorrhage, the pyruvate group had better cardiovascular and cerebrovascular function with significantly higher systemic and cerebral oxygen consumption and less attenuation of the amplitude and frequency of the electrocorticogram. In addition, pyruvate prevented metabolic acidosis and stabilized the L/P. Pyruvate slowed the rise in neocortical microdialysis levels of ADO + HX + Ino, and prevented the net efflux of ADO + HX + Ino into the sagittal sinus. The findings reveal considerable metabolic and functional enhancement by pyruvate during severe hemorrhagic shock with a 75-min delay in spontaneous cardiovascular decompensation and death.
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PMID:Intravenous pyruvate prolongs survival during hemorrhagic shock in swine. 1060 Aug 44

We review the information obtained by 13C NMR methods on the metabolic compartmentation of the adult mammalian brain with emphasis on its quantitative aspects. Classical radiotracer evidence and more recent 13C NMR results support the presence in the brain of at least two glutamate pools, small and large, associated with two kinetically different tricarboxylic acid cycles localized in glia and neurons, respectively. Neuronal and glial cycles interact closely, utilizing common substrates like glucose and oxygen and exchanging a variety of metabolites including glutamate, glutamine and GABA. A model for the cerebral metabolism of (1,2-13C2) acetate has made it possible to calculate fluxes through both cycles and evaluate the exchanges of glutamate, glutamine and GABA under different physiopathological conditions. Calculated flux values through the neuronal and glial tricarboxylic acid cycles are 1.0 and 0.4 mumol/min g, respectively. In the adult normoxic brain, the small and large glutamate pools account for approximately 10% and 90% of cerebral glutamate with estimated turnover times of 1.25 and 5.8/min, respectively. Net transfers of neuronal glutamate and GABA to the glial compartment are calculated to be 0.1 and 0.04 mumol/min g while transfer of glial glutamine to the neuronal compartment is estimated as 0.1 mumol/min g. Pyruvate recycling in the adult brain occurs mainly in the synaptic terminals with a calculated flux of 0.3 mumol/min g. These flux values are altered severely in pathological states such as hypothyroidism or ischemia.
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PMID:Quantitative 13C NMR studies of metabolic compartmentation in the adult mammalian brain. 1065 92

Pyruvate, a metabolic product of glycolysis and an oxidizable fuel in myocardium, increases cardiac mechanical performance and energy reserves, especially when supplied at supraphysiological concentrations. The inotropic effects of pyruvate are most impressive in hearts that have been reversibly injured (stunned) by ischemia/reperfusion stress. Glucose appears to be an essential co-substrate for pyruvate's salutary effects in stunned hearts, but other fuels including lactate, acetate, fatty acids, and ketone bodies produce little or no improvement in postischemic function over glucose alone. In contrast to pharmacological inotropism by catecholamines, metabolic inotropism by pyruvate increases cardiac energy reserves and bolsters the endogenous glutathione antioxidant system. Pyruvate enhancement of cardiac function may result from one or more of the following mechanisms: increased cytosolic ATP phosphorylation potential and Gibbs free energy of ATP hydrolysis, enhanced sarcoplasmic reticular calcium ion uptake and release, decreased cytosolic inorganic phosphate concentration, oxyradical scavenging via direct neutralization of peroxides and/or enhancement of the intracellular glutathione/NADPH antioxidant system, and/or closure of mitochondrial permeability transition pores. This review aims to summarize evidence for each of these mechanisms and to consider the potential utility of pyruvate as a therapeutic intervention for clinical management of cardiac insufficiency.
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PMID:Pyruvate: metabolic protector of cardiac performance. 1065 16

Myocardial ischemia-reperfusion is associated with bursts of reactive oxygen species (ROS) such as superoxide radicals (O(2)(-).). Membrane-associated NADH oxidase (NADHox) activity is a hypothetical source of O(2)(-)., implying the NADH concentration-to-NAD(+) concentration ratio ([NADH]/[NAD(+)]) as a determinant of ROS. To test this hypothesis, cardiac NADHox and ROS formation were measured as influenced by pyruvate or L-lactate. Pre- and postischemic Langendorff guinea pig hearts were perfused at different pyruvate/L-lactate concentrations to alter cytosolic [NADH]/[NAD(+)]. NADHox and ROS were measured with the use of lucigenin chemiluminescence and electron spin resonance, respectively. In myocardial homogenates, pyruvate (0.05, 0.5 mM) and the NADHox blocker hydralazine markedly inhibited NADHox (16 +/- 2%, 58 +/- 9%). In postischemic hearts, pyruvate (0.1-5.0 mM) dose dependently inhibited ROS up to 80%. However, L-lactate (1.0-15.0 mM) stimulated both basal and postischemic ROS severalfold. Furthermore, L-lactate-induced basal ROS was dose dependently inhibited by pyruvate (0.1-5.0 mM) and not the xanthine oxidase inhibitor oxypurinol. Pyruvate did not inhibit ROS from xanthine oxidase. The data suggest a substantial influence of cytosolic NADH on cardiac O(2)(-). formation that can be inhibited by submillimolar pyruvate. Thus cytotoxicities due to cardiac ischemia-reperfusion ROS may be alleviated by redox reactants such as pyruvate.
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PMID:Antioxidant pyruvate inhibits cardiac formation of reactive oxygen species through changes in redox state. 1104 81

Normal cardiac function requires adequate oxygen and substrate (fatty acids, glucose lactate) supply for the energetic requirements of the myocardium. Ischaemia induces abnormalities in the production and excretion of products of myocardial metabolism. During ischaemia, the equilibrium which exists during aerobic respiration between the beta-oxidation of fatty acids and carbohydrates and which generates ATP is disturbed. Pyruvate oxidation and beta-oxidation of fatty acids decrease, and ATP is mainly produced by anaerobic glycolysis. Under these conditions, intracellular glycogen is mobilised, the lactate and protons accumulate in the cardiomyocyte. If reperfusion occurs before irreversible lesions are produced, then functional recovery is possible and is mostly dependant on the type of energetic substrate available. Circulating fatty acids are produced in large quantities after ischaemia: their beta-oxidation, which is then the principal source of ATP, may contribute to the aggravation of contractile dysfunction during reperfusion and accentuate or generate arrhythmias. The decoupling between acceleration of anaerobic glycolysis and the defect of pyruvirate oxidation (inhibition of pyruvirate dehydrogenase) participate in a significant fashion to the accumulation of protons. Rapid correction of intracellular acidosis during reperfusion by activation of the Na+/H+ exchanger, coupled with the accumulation of intracellular Na+ induces a deleterious calcium overload via the Na+/Ca++ exchanger. These different aspects of intracellular metabolism constitute pharmacological targets for the development of future cardio-protective agents.
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PMID:[Myocardial metabolism abnormalities during ischemia and reperfusion]. 1122 23

Reactive oxygen species (ROS) have been implicated in the pathogenesis of the structural and functional alterations to tissues that are associated with a variety of pathological processes, including: sepsis and septic shock, thermal injury, doxorubicin-induced cardiomyopathy, hemorrhagic shock, and mesenteric ischemia/reperfusion (I/R) injury. Pyruvate (CH3COCOO-), a small molecule that is normally regarded as a key intermediate in the oxidative or anaerobic metabolism of glucose, is also a potent and effective ROS scavenger. Unfortunately, the usefulness of pyruvate as a therapeutic agent is abrogated by its very poor stability in solution. In an effort to take advantage of the ability of pyruvate to scavenge ROS while avoiding the problems associated with the instability of pyruvate in solution, we have developed a novel resuscitation fluid, which consists of a simple derivative of pyruvic acid, ethyl pyruvate, dissolved in a calcium-containing balanced salt solution. We call this solution Ringer's Ethyl Pyruvate Solution (REPS), and have shown in preliminary studies that treatment with REPS can improve outcome in a variety of animal models of critical illness.
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PMID:Ringer's ethyl pyruvate solution: a novel resuscitation fluid. 1137 8

Pyruvate (PY) is a 3-carbon compound present in human tissues and physiologically used by cells as an energetic substrate in anaerobic conditions. In the last few years, we have successfully used PY to protect small bowel (SB), liver, and kidneys from ischemia/reperfusion injury in several experimental models. Although the mechanism of protection is not fully clarified, we have shown increased tissue levels of adenosine triphosphate (ATP) during ischemia. This suggests that providing supra-physiologic concentrations of PY during anaerobic glycolysis might enable the cells to remain viable during prolonged hypoxia. Furthermore, mechanisms such as direct inhibition of oxygen free radical formation, abrogation of neutrophilic infiltration and reduced up-regulation of adhesion molecules have also been documented in these studies. In light of these findings, we evaluated the efficacy of PY in organ preservation and transplantation. We demonstrated a protective effect on intestinal preservation injury and during acute rejection. Oral PY treatment induced immunologic changes in rejecting allograft, inhibiting perforin and granzyme-b expression and leukocytic infiltration. Protection was also documented on livers after prolonged hypothermic preservation using a PY based preservation solution. Additionally, isolated pancreatic islets were cultured in PY enriched media and maintained viable for up to 120 days followed by in vitro testing and transplantation revealing a well preserved function. All these findings suggest that PY is a potentially beneficial nutrient in patients undergoing organ transplantation and that future clinical application of PY in this field should be encouraged.
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PMID:Pyruvate in organ transplantation. 1143 53

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