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

Astrocytic swelling after ischemic insult has been considered a sign of parturbed cell viability. Investigations using cultured astrocytes and C6 glioma cells have revealed that viable astrocytes swell, spatially buffering various metabolites which are increased by the metabolic turmoil following ischemic insults. In the present study, we have studied the temporal profile of ultrastructural changes of astrocytes in the cerebral cortex associated with progressive selective neuronal, death where infarction is not induced. We occluded the left carotid artery of the Mongolian gerbil twice for 10 minutes at a 5 hr interval. In this model, following reperfusion, selective neuronal death progresses in the coronal section cut at the infundibular level. The whole brains of the sham operated control and postischemic animals were fixed by transcardiac perfusion of glutaraldehyde fixatives, at 15 min, 5 and 12 hr after the 2nd 10 min ischemia. Ultrathin sections including the 3rd and 5th cortical layers were prepared from the cut surface at the level of infundibulum. Mild swelling of astrocytic processes and perivascular end-feet was observed in the 15 min group. Glycogen granules were not prominent. In the 5 hr group, we found a few necrotic neurons disseminated in the cortex. All astrocytic cell processes were swollen with increased number of glycogen granules, especially marked in the perivascular end-feet. In the 12 hr group, necrotic neurons increased in number, astrocytic swelling was more extensive, and glycogen granules were evident in astrocytes. No cellular destruction was observed. We conclude: 1. Swelling progresses in astrocytes which however still remain viable and this process is associated with selective progression of neuronal death. 2. Glycogen granules increase in the swollen yet viable astrocytic cell processes.
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PMID:Ultrastructure of astrocytes associated with selective neuronal death of cerebral cortex after repeated ischemia. 941 74

Glycogen and its turnover are important components of myocardial glucose metabolism that significantly impact on postischemic recovery. We developed a method to measure glycogen turnover (rates of glycogen synthesis and degradation) in isolated working rat hearts using [3H]- and [14C]glucose. In aerobic hearts perfused with 11 mM glucose, 1.2 mM palmitate, and 100 microU/ml insulin, rates of glycogen synthesis and degradation were 1.24 +/- 0.3 and 0.53 +/- 0. 25 micromol. min-1. g dry wt-1, respectively. Low-flow ischemia (0.5 ml/min, 60 min) elicited a marked glycogenolysis; rates of glycogen synthesis and degradation were 0.54 +/- 0.16 and 2.12 +/- 0.14 micromol. min-1. g dry wt-1, respectively. During reperfusion (30 min), mechanical function recovered to 20% of preischemic values. Rates of synthesis and degradation were 1.66 +/- 0.16 and 1.55 +/- 0. 21 micromol. min-1. g dry wt-1, respectively, and glycogen content remained unchanged (25 +/- 3 micromol/g dry wt). The assessment of glycogen metabolism needs to take into account the simultaneous synthesis and degradation of glycogen. With this approach, a substantial turnover of glycogen was detectable not only during aerobic conditions but also during ischemia as well as reperfusion.
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PMID:Assessment of glycogen turnover in aerobic, ischemic, and reperfused working rat hearts. 981 58

In order to highlight severity of myocardial injury during the course of global ischemia and reperfusion, cytochemistry of glycogen and succinate dehydrogenase (SDH) as well as hematoxylin and eosin staining (H & E) and electron microscopy were observed in canine myocardium. Seven mongrel dogs were selected for reperfusion injury after global ischemia in this study. Myocardial biopsies were taken from the anterior wall of the left ventricle (a) after cardiopulmonary bypass (the first biopsy); (b) at the end of the aortic crossclamp (the second biopsy); and (c) 30 minutes after crossclamp removal (the third biopsy). All biopsies were cytochemically assessed, and the latter two, for electron microscopic studies. The averages of myocardial necrotic rate and surface to volume ratio of myocardial mitochondria were calculated under electron microscopy and in electron microscopic slices, respectively. Myofibrillae were of normal morphology in the first biopsy; in wave-shape and partly vacuolated, with large and deformed nuclei in the second one; and in wave-shape and severely vacuolated in the third one, in H & E. Glycogen granules were variously stained in moderate, weak and intensive positive reactions in the three biopsies respectively in glycogen staining. SDH was stained in intensive, weak, and moderate positive reactions in three, respectively. By electron microscopy, Z bands twisted severely, and local dissolution of cristae and matrix occurred in a minority of the mitochondria in the second biopsy; and majority of the Z bands in necrotic region had disappeared, the myofibrillae were obscure and patchily dissolved. Clustered and deformed mitochondria could be found in the third biopsy. Significant difference could be noted between the averages of the second and third biopsies (14.88 +/- 3.09% vs. 60.25 +/- 8.55%, p < 0.001). The surface to volume ratio of the ischemic mitochondria was much bigger than that of the reperfused (3.95 +/- 1.09 micron-1 vs. 2.77 +/- 0.93 micron-1, p = 0.041). Myocardial injury was more severe in reperfusion than in ischemia myocardium. There were correlations between histobiochemical and ultrastructural alterations in damaged canine myocardium.
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PMID:Cytochemistry and ultrastructure of canine myocardium undergoing global ischemia and reperfusion injury. 1006 88

Astrocytic subtypes in different cortical regions of injured human cerebral cortex of 22 patients with brain trauma, vascular anomalies and brain tumours have been examined by means of light microscopy and conventional transmission electron microscopy. The cortical biopsies of frontal, parietal and temporal cortex were examined to analyse the heterogeneous astrocytic response and characterize astrocytic population subtypes. Swollen clear and dense astrocytes, glycogen rich- and glycogen-depleted astrocytes, aged or lipofucsin rich-astrocytes and reactive, dark, hypertrophic astrocytes were identified. Clear and dense astrocytes displayed bundles of glial filaments and dense inclusion bodies. Glycogen-rich astrocytes exhibited an accumulation of beta type of monogranular glycogen granules, which disappear in the glycogen-depleted astrocytes, suggesting anoxic mobilization of glycogen stores during ischemia or anoxia. Lipofucsin rich astrocytes were mainly related with ageing processes, although their presence in young patients suggests also an injured related process. Dark astrocytes with phagocytic properties were found. They exhibited bundles of glial filaments. The astrocytic response depended upon the nature of cortical insult, extent of damage, time course of pathological lesion and affected cortical region.
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PMID:Astrocyte subtypes in the gray matter of injured human cerebral cortex: a transmission electron microscope study. 1023 May 30

Experimental evidence indicates a metabolic basis of contraction-perfusion coupling during an increase in cardiac work load. This study aims to characterize adjustment of myocardial energy metabolism in response to acute low flow ischemia (LFI), and to determine its involvement in perfusion-contraction coupling. Intracellular parameters were measured in isolated rat hearts by NMR spectroscopy and biochemical methods during 30 min of graded LFI and reperfusion as compared to continuous perfusion (control). Oxygen pressure was set to reach maximal oxygen extraction at 70% coronary flow rate (CFR), therefore oxygen limitation was proportional to coronary underperfusion. At 69, 38 and 10% CFR left ventricular pressures decreased to 71, 43 and 25% of pre-ischemic values respectively (P<0.005 v 97% in control) without an increase in diastolic tone, and recovered to 92+/-3% after 30 min of reperfusion. Despite hydrolysis of high energy phosphates and cellular acidification, ADP concentrations were stable in underperfused hearts. At 69, 38 and 10% CFR, cytosolic phosphorylation potentials (PP) decreased from 74+/-10 m M(-1)during pre-ischemia to 40+/-6, 25+/-4 and 14+/-4 m M(-1)respectively (P<0.05 v 63+/-9 m M(-1)in control), and lactate efflux increased to 256+/-18, 386+/-22 and 490+/-43 micromol /gdw respectively (P<0.005 v 186+/-22 micromol/gdw in control). Glycogen contents decreased (P<0.005 v control) and accounted for 27-30% of lactate efflux. These results indicate: (a) proportionate depression of contraction force and glycogen contents, and increased glucose uptake and anaerobic energy production in the underperfused myocardium. Coordinated modulation of these parameters attributes cytosolic PP a regulatory function; (b) resetting of cytosolic PP to lower levels mediates perfusion-contraction coupling during graded LFI. The data are consistent with the concept that glycolytic energy production improves myocardial tolerance to ischemia.
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PMID:Sensitivity of mechanical and metabolic functions to changes in coronary perfusion: A metabolic basis of perfusion-contraction coupling. 1077 84

Adenosine inhibits glycolysis from exogenous glucose, reduces proton production and enhances post-ischemic left ventricular minute work (LV work) following ischemia in isolated working rat hearts perfused with glucose and fatty acids. In hearts partially depleted of glycogen by antecedent ischemic stress (AIS)--two cycles of ischemia (10 min) and reperfusion (5 min)--adenosine stimulates rather than inhibits glycolysis, increases proton production and worsens recovery of post-ischemic LV work. We determined if the switch in adenosine effect on glycolysis and recovery of LV work following ischemia in hearts subject to AIS was due to the reduction in glycogen content per se or because of alpha-adrenoceptor stimulation. One series of hearts underwent a 35-min period of substrate-free Langendorff perfusion (substrate-free glycogen depletion; SFGD) and a second series of hearts was subjected to AIS. Both series of hearts had a similar glycogen content (approximately 70 micromol/g dry wt) prior to drug treatment. In SFGD hearts perfused aerobically, adenosine (500 microM) inhibited glycolysis from exogenous glucose and reduced proton production. In SFGD hearts reperfused after prolonged ischemia, adenosine exerted similar effects on glucose metabolism and enhanced recovery of post-ischemic LV work (87.2 +/- 2.2% of preischemic values) relative to untreated hearts (25.9 +/- 13.3% of preischemic values). In AIS hearts perfused aerobically or subject to ischemia and reperfusion, phentolamine (1 microM) given in combination with adenosine, prevented adenosine-induced stimulation of glycolysis from exogenous glucose and reduced calculated proton production from glucose. Recoveries of post-ischemic LV work in AIS hearts for untreated, adenosine, phentolamine and adenosine/phentolamine groups were 34.4 +/- 11.4%, 8.6 +/- 3.9%, 16.3 +/- 13.5% and 73.2 +/- 13.1% respectively, of preischemic values. Glycogen depletion in the absence of ischemia does not switch the effect of adenosine from inhibition to stimulation of glycolysis or alter the cardioprotective properties of adenosine in hearts subject to ischemia and reperfusion. The detrimental switch in the metabolic and cardioprotective effects of adenosine, in hearts subject to AIS, can be prevented by phentolamine, an alpha-adrenoceptor antagonist. These data support the concept that modulation of glucose metabolism is an important factor in the mechanical functional recovery of the post-ischemic heart.
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PMID:Phentolamine prevents the adverse effects of adenosine on glycolysis and mechanical function in isolated working rat hearts subjected to antecedent ischemia. 1088 59

Diabetic hearts are suggested to exhibit either increased or lower sensitivity to ischemia. Detrimental effects of prolonged ischemia can be attenuated by preconditioning, however, relatively little is known about its effects in the diseased myocardium. This study was designed to test the susceptibility to ischemia-induced arrhythmias and the effect of preconditioning in the diabetic heart. Rats were made diabetic with streptozotocin (45 mg/kg, i.v.). After 1 week, isolated Langendorff-perfused hearts were subjected to 30 min occlusion of LAD coronary artery without or with preceding preconditioning induced by one cycle of 5 min ischemia and 10 min reperfusion. Glycogen and lactate contents were estimated in the preconditioned and non-preconditioned hearts before and after ischemia. Diabetic hearts were more resistant to ischemia-induced arrhythmias: incidence of ventricular tachycardia (VT) decreased to 42% and only transient ventricular fibrillation (VF) occurred in 17% of the hearts as compared to the non-diabetic controls (VT 100% and VF 70% including sustained VF 36%; p < 0.05). Preconditioning effectively suppressed the incidence and severity of arrhythmias (VT 33%, VF 0%) in the normal hearts. However, this intervention did not confer any additional protection in the diabetic hearts. Despite higher glycogen content in the diabetic myocardium and greater glycogenolysis during ischemia, production of lactate in these hearts was significantly lower than in the controls. Preconditioning caused a substantial decrease in the accumulation of lactate in the normal hearts, whereby in the diabetic hearts, this intervention did not cause any further reduction in the level of lactate. In conclusion, diabetic rat hearts exhibit lower susceptibility to ischemic injury and show no additional response to preconditioning. Reduced production of glycolytic metabolites during ischemia can account for the enhanced resistance of diabetic hearts to ischemia as well as for the lack of further protection by preconditioning.
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PMID:Acute diabetes modulates response to ischemia in isolated rat heart. 1097 67

Experimental evidence indicates that ischemic glycolysis improves myocardial tolerance to low flow ischemia and anoxia, and cellular membrane disruption signals and/or causes transition to irreversible ischemic injury. The objective of this study was to determine the impact of ischemic glycolysis on membrane integrity and myocardial viability during total ischemia. Phosphorus metabolites were measured by 31P NMR spectroscopy and cellular volumes were determined by 1H and 59Co NMR in conjunction with the extracellular marker cobalticyanide. Isolated rat hearts were submitted to 30 min of total ischemia, followed by 30 min of reperfusion. Glycogen contents were modulated by pre-ischemic perfusion with various substrates. Increased glycolytic activities, as determined from lactate production, delayed onset of ischemic contracture (p < 0.05), induced cytosolic acidification (p < 0.005) and cellular swelling during ischemia (p < 0.05), reduced post-ischemic diastolic tone (p < 0.05), improved recovery of high energy phosphates and contraction force (p < 0.005). Inhibition of glycolysis with iodoacetate and glycogen depletion with 2-deoxyglycose resulted in early onset of ischemic contracture (p < 0.005), elevated post-ischemic diastolic pressures (p < 0.05), reduced coronary flow rates and mechanical activities (p < 0.05). Cellular viability was evaluated by creatine kinase efflux, and membrane integrity was determined from cellular swelling during perfusion with hypoosmotic medium. High activities of ischemic glycolysis correlated with improved cellular viability and preserved membrane integrity, while low glycolytic fluxes were associated with membrane permeabilization (p < 0.05). The protective effect of ischemic glycolysis over sarcolemmal integrity was attributed to continuous provision of energy, undetected by 31P NMR spectroscopy. There was no evidence that ischemic swelling caused by glycolytic end-metabolites accumulation had detrimental consequences, and of excessive swelling during reperfusion. It is concluded that one of the cardio-protective mechanisms of ischemic glycolysis is energy-dependent preservation of sarcolemmal integrity and cellular viability.
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PMID:Glycolysis protects sarcolemmal membrane integrity during total ischemia in the rat heart. 1177 80

We examined changes induced during ischemia-reperfusion on myocardial metabolism and function by oxygenated warm cardioplegia (CP) and ischemic preconditioning (IP). The postischemic hemodynamic recovery was comparable and significantly better in IP and CP groups, than in untreated hearts (e.g., LVDP recovery was threefold that of the control). The IP hearts reached a pH plateau earlier during ischemia and at considerably higher pH value (pH approximately 6) compared to the other groups (pH approximately 5.5). Postischemic phosphocreatine (PCr) and ATP recoveries were comparable and better in protected groups (approximately 72% and approximately 30% vs approximately 25% and approximately 10% in control, p < 0.0001). Preischemic glycogen was significantly reduced in IP to 49% and increased in CP hearts to 127%. However, the lactate levels at the end of ischemia were similar in all the groups, indicating glucose utilization from extracellular space during ischemia in IP hearts. Thus, similar hemodynamic protection by CP and IP is observed despite increased energy depletion during ischemia in IP. IP and CP protection is expressed through better energetic status and by higher recovery of the TCA cycle activity or enhanced mitochondria-cytosol transport of alpha-ketoglutarate on reperfusion in addition to metabolic changes during ischemia. Glycogen store recovered significantly better in IP than in CP and Control. These results exhibit similar and improved postischemic hemodynamic protection by CP and IP. Increased recovery of postischemic glycogen pool is a protective feature of IP, whereas slightly higher lactate metabolism during reperfusion is a protection component of CP.
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PMID:Glucose metabolism, energetics, and function of rat hearts exposed to ischemic preconditioning and oxygenated cardioplegia. 1248 6

Cooperation between astrocytes and neurons is a unique interaction between two highly specialized cell types of the brain. Therefore, lack of nutrient supply during ischemia requires tight coordination of metabolism between astrocytes and neurons to keep the brain functions intact. To understand the impact of energy limitation on astrocytes, the functions of astrocytes have to be considered: (i) supplementation of neuronal cells, (ii) modulation of the extracellular milieu, mainly of the glutamate level, and (iii) elimination of reactive oxygen species (ROS). In cultured astrocytes and neurons inhibition of oxidative phosphorylation, using rotenone, was tested. Interestingly, this had only a negligible effect on Ca2+ homeostasis in astrocytes, even in combination with a severe glutamate stress. In contrast, in neurons glutamate in the presence of rotenone induced Ca2+ deregulation. Ca2+ homeostasis is very critical for cell survival. A massive and prolonged Ca2+ rise will lead to deregulation of many processes in such a way that the cells affected can hardly survive. Ca2+ homeostasis depends on the energy-consuming processes, which maintain the steep gradient between intracellular and extracellular Ca2+ concentration. Deprivation of oxygen and glucose during ischemia leads to a depletion of ATP in the brain, due to inhibited glycolytic and mitochondrial activity, whereas energy-consuming processes like ion pumps drain the ATP pools. On the other hand, specific mechanisms can protect brain structures against the massive insult of ischemia. Glycogen, stored in astrocytes, can maintain both neurons and astrocytes alive during short limitation of oxygen and glucose. Moreover, astrocytes can fuel ATP generation by providing lactate for neurons.
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PMID:Glial perspectives of metabolic states during cerebral hypoxia--calcium regulation and metabolic energy. 1526 85


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