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

Mitoplasts were prepared from 3-h ischemic livers in an attempt to define the structural alterations in the inner membrane that may account for the functional deficiencies of ischemic mitochondria. Mitoplasts from both control and ischemic livers had similar specific activities of cytochrome oxidase and succinate-cytochrome c reductase. With both preparations, the specific activity of rotenone-insensitive NADH-cytochrome c reductase was 10-fold lower than in the mitochondria from which they were prepared. Ischemic mitoplasts had no respiratory control with ADP, and had a slightly reduced phospholipid to protein ratio and an increased cholesterol to protein ratio. As a result, the cholesterol to phospholipid molar ratio was increased from the control of 0.04 to 0.08. There were also differences in the content of individual phospholipid species. Phosphatidylcholine increased by 15%, while cardiolipin decreased by 60%. There were increases in sphingomyelin and in the lysophospholipids of phosphatidylcholine, ethanolamine, and cardiolipin. Pretreatment with chlorpromazine did not prevent these changes. Linoleic acid was decreased by 35% in ischemic phospholipids, and the content of free fatty acids was increased 4-fold. Electron spin resonance spectroscopy of mitoplasts spin labeled with either 5- or 12-doxyl stearic acid revealed an increased molecular order (decreased fluidity) of ischemic inner mitochondrial membranes consistent with the increased cholesterol to phospholipid ratio. The data indicate activation of a phospholipase A in ischemic mitochondria with the resulting accumulation of products of lipid hydrolysis. This conclusion further emphasizes the close similarity between the structural and functional consequences of ischemia in the intact animal and the effect on isolated mitochondria of the activation of the endogenous phospholipase A. In both cases the major functional alterations are attributable to changes in the permeability of the inner mitochondrial membrane induced by the accumulation of lysophospholipids.
 ...
PMID:Structural alterations of the inner mitochondrial membrane in ischemic liver cell injury. 298 20

The structural and functional heterogeneity of mitochondria isolated from intact and ischemic (after 60 min exposure at 37 degrees C) rabbit myocardium was evaluated. In the presence of cytochrome c. a relatively high (260 +/- 26 ng at O/min . mg of protein) rate of rotenone-sensitive NADH oxidation was observed, which was increased in ischemia. Cytochrome c stimulated the increase of NADH oxidation in mitochondria of normal and ischemic myocardium by the factors of 3.5 and 3.4, respectively. Succinate oxidation in the presence of bromthymol blue in normal and ischemic myocardium mitochondria was activated by cytochrome c 3.3- and 2.9-fold, respectively. The percentage of mitochondria with both structurally damaged membranes was 15% and 25% in normal and ischemic myocardium preparations, respectively. In the absence of ADP, cytochrome c contributed to the increase of the succinate oxidase activity in ischemic mitochondria; that in the 3rd state was inhibited in ischemia and normalized by cytochrome c. A principle was proposed for estimating the percentage of mitochondria with damaged outer membranes, the indices being equal to 34% in control and to 56% in ischemic myocardium. Evidence was obtained suggesting that this mitochondrial fraction was characterized by lowered coupling and absence of rotenone-sensitive NADH: oxidase activity. The percentage of intact mitochondria, in which succinate oxidation is inhibited by bromthymol blue and does not need exogenous cytochrome c, is 51% in control and 19% in ischemic myocardium mitochondria.
 ...
PMID:[Evaluation of structuro-functional heterogeneity of isolated mitochondria from the normal and the ischemic myocardium]. 300 Apr 62

An increase in cytosolic free calcium concentration ([Ca2+]i) may trigger irreversible cell injury following cerebral ischemia. We have measured changes in [Ca2+]i in cat cortex in vivo during ischemia produced by 1 hour of middle cerebral artery occlusion and during 30 minutes of reperfusion. Indo-1, a fluorescent Ca2+ indicator, was loaded into the exposed cortex by superfusion, and changes in the [Ca2+]i signal (400/506 nm ratio) were measured microfluorometrically during ultraviolet excitation (340 nm). The nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD/NADH) redox state and hemodynamic changes were measured simultaneously. The animals showing severe deterioration in their electroencephalograms (EEG) showed a progressive increase in the [Ca2+]i signal during ischemia (baseline: 1.46 +/- 0.05; 60 minutes after occlusion: 2.99 +/- 0.37; n = 7). At 30 minutes following reperfusion, the animals showing little recovery in their EEG exhibited a further increase in [Ca2+]i (4.71 +/- 0.87, n = 3), whereas animals showing significant recovery in their EEG also showed recovery of [Ca2+]i (1.55 +/- 0.09, n = 4). By contrast, the moderate or mild stroke animals with less deterioration in their EEGs showed no increase in [Ca2+]i during either ischemia or reperfusion. These data suggest that the increase in [Ca2+]i might be closely related not only to deterioration of brain function during ischemia but also to poor recovery during the reperfusion period.
 ...
PMID:In vivo measurement of cytosolic free calcium during cerebral ischemia and reperfusion. 314 14

Thirty minutes of warm hepatic ischemia produced by portal triad cross-clamping was repeated five times at 30-minute intervals in three groups of five dogs each: Group A was subjected only to portal triad cross-clamping; Group B received simultaneous clamping of the celiac axis and the superior mesenteric artery; and Group C had a simultaneous splenojugular shunt. The arterial blood ketone body ratio (acetoacetate/beta-hydroxybutyrate: KBR), reflecting the NAD+/NADH ratio in liver mitochondria, decreased significantly after each cross-clamping in all groups. After the first declamping, there was no significant difference in the recovery rate of the KBR among the three groups. After the second declamping, the recovery rate in Group A decreased significantly compared with the rates of Groups B and C (P less than 0.05). After the fourth declamping, the recovery rate in Group B was significantly lower than that of Group C (P less than 0.05). The hepatic energy charge [(ATP + 1/2ADP)/(ATP + ADP + AMP)] 30 minutes after the fifth declamping decreased significantly to 0.75 +/- 0.01 in Group A, compared with 0.84 +/- 0.01 in Group C (P less than 0.01). The lactate and total free plasma amino acid levels in the arterial blood increased significantly in the order of Groups A, B, and C. It is suggested that the inflow of stagnant portal venous blood to ischemic liver impairs hepatic energy metabolism.
 ...
PMID:Deleterious effects of splanchnic congestion on hepatic energy metabolism following repeated portal triad cross-clamping in dogs. 319 65

Gerbils of both sexes were used to study the effects of 30-min ischemia and subsequent recirculation for 4 and 8 days. The mortality rate was 9% during ischemia and 34% in the recirculation period. No close correlation was found between the extent of metabolic changes and the severity of clinical signs after ischemia. Gerbils exhibited severe clinical signs with metabolic patterns of severe hypoxic damage, but with only slight biochemical changes as well, stressing the necessity of detailed examination in regional metabolic studies. According to planimetrical evaluation the most sensitive indicator of ischemic damage was alteration in pH. Decrease in pH without changes in ATP and NADH was associated with severe clinical signs. Biochemical changes were demonstrated after recirculation in some gerbils having severe clinical signs at the end of the ischemic period. The changes in pH and potassium found 8 days after the ischemic insult stress that a 30-min focal ischemia might have long lasting, perhaps irreversible consequences.
 ...
PMID:The vulnerability of gerbils to focal cerebral ischemia. Neurological signs and regional biochemical changes after ischemia and recirculation. 321 13

A new luminescence procedure based on the creatine kinase reaction was developed for measuring creatine in plasma. The method is highly applicable to small animal work where the amount of blood volume is critical. Only 20 microliter of sample is necessary for creatine analysis. Deproteinizing the plasma sample with ethanol at room temperature is convenient. This extraction method is adaptable to a clinical setting. The ethanol used in the extraction is compatible with the luminescence method but precipitated enzymes in the NADH spectrophotometric method because of the greater sample volume needed for analysis. The creatine concentration is stable in plasma for at least 1 hr in a final anticoagulant concentration of 10 mM EDTA. The correlation between the new luminescence method with the established NADH spectrophotometric method was excellent (r = 0.99). The accuracy of the within-run precision is high, with a mean coefficient of variation, 2-3%. Plasma creatine levels could be an important indicator denoting early cellular damage and of potential prognostic value. Preliminary studies in human muscle ischemia and early shock in rabbits revealed a significant increase in plasma creatine levels. Further investigations are necessary to evaluate its clinical importance.
 ...
PMID:Plasma creatine determination using a luminescence method. 339 6

It has been demonstrated that perfusion of myocardium with glutamic acid or tricarboxylic acid cycle intermediates during hypoxia or ischemia, improves cardiac function, increases ATP levels, and stimulates succinate production. In this study isolated adult rat heart cells were used to investigate the mechanism of anaerobic succinate formation and examine beneficial effects attributed to ATP generated by this pathway. Myocytes incubated for 60 min under hypoxic conditions showed a slight loss of ATP from an initial value of 21 +/- 1 nmol/mg protein, a decline of CP from 42 to 17 nmol/mg protein and a fourfold increase in lactic acid production to 1.8 +/- 0.2 mumol/mg protein/h. These metabolite contents were not altered by the addition of malate and 2-oxoglutarate to the incubation medium nor were differences in cell viability observed; however, succinate release was substantially accelerated to 241 +/- 53 nmol/mg protein. Incubation of cells with [U-14C]malate or [2-U-14C]oxoglutarate indicates that succinate is formed directly from malate but not from 2-oxoglutarate. Moreover, anaerobic succinate formation was rotenone sensitive. We conclude that malate reduction to succinate occurs via the reverse action of succinate dehydrogenase in a coupled reaction where NADH is oxidized (and FAD reduced) and ADP is phosphorylated. Furthermore, by transaminating with aspartate to produce oxaloacetate, 2-oxoglutarate stimulates cytosolic malic dehydrogenase activity, whereby malate is formed and NADH is oxidized. In the form of malate, reducing equivalents and substrate are transported into the mitochondria where they are utilized for succinate synthesis.
 ...
PMID:Evidence for succinate production by reduction of fumarate during hypoxia in isolated adult rat heart cells. 342 43

To evaluate the diagnostic role of histochemically demonstrated aerobic dehydrogenases in ischemic myocardial injury NADH-diaphorase, succinate dehydrogenase (SDH), beta-hydroxybutyrate dehydrogenase (HBDH) and malate dehydrogenase (MDH) were demonstrated histochemically and the corresponding enzyme activities were measured biochemically in isolated perfused rats hearts after global ischemia from 0 to 12 h. The present data show that the enzyme-histochemical methods when used properly are more sensitive indicators of early ischemic injury than classical histological staining procedures. From the enzymes tested here the histochemical demonstration of HBDH turned out to be best suited for use when suspecting ischemic myocardial injury at autopsy.
 ...
PMID:Oxidative enzyme activities and respective histochemical reactions in ischemic rat myocardium. 342 4

The enzyme xanthine: acceptor oxidoreductase found in rat heart equilibrates between three forms differing in electron acceptor specificity. Form D transfers electrons exclusively to NAD+ and accounts for 85% of total oxidoreductase activity. Form O transfers electrons to molecular oxygen and accounts for 8%. The D/O form prefers NAD+, but without NAD+ transfers electrons to oxygen. Interconversion from D to O and O to D forms is catalyzed by sulfhydryl group-modifying reagents: Cd2+, Cu2+, disulfiram, and heating with dithiothreitol. This suggests that sulfhydryl groups participate in the first stage of enzyme conversion. The NADH/NAD+ concentration ratio may regulate the dehydrogenase activity of xanthine:acceptor oxidoreductase (NAD+-dependent activity of D and D/O forms). Accumulating NADH inhibits hypoxanthine hydroxylation. The amount of form O increases during cardiac ischemia, facilitating superoxide radical-ion generation. Also, NADH/NAD+ does not regulate form O, promoting adenylate nucleotide pool depletion, especially in the heart which has low de novo purine nucleotide synthesis.
 ...
PMID:Three forms of xanthine: acceptor oxidoreductase in rat heart. 346 36

Brain levels of NADH and NAD+ were measured in three models of cerebral ischemia to determine whether degradation of the pyridine nucleotides is enhanced in models that generate high concentrations of lactic acid. Complete ischemia (decapitation), in which lactate increased to 14 mmol/kg, caused a gradual decrease in the NAD pool to 50% of control by 2 h. During focal ischemia (occlusion of the middle cerebral artery), the decrease in the NAD pool was less pronounced (82% of control at 2 h) despite the accentuated accumulation of lactate to 33 mmol/kg. In a third model (unilateral hypoxia-ischemia), pretreatment of animals with glucose augmented the ischemic elevation of lactate from 30 mmol/kg to 40 mmol/kg and greatly impaired restoration of energy metabolites during recirculation. However, glucose pretreatment had no effect on the size of the NAD pool during ischemia or early recovery. These results, therefore, demonstrate that the pyridine nucleotide pool is not rapidly degraded during ischemic insults that accumulate high concentrations of lactic acid. The stability of the NAD pool may have been enhanced by the limited increase in brain levels of NADH that occurred in these models of incomplete ischemia.
 ...
PMID:Effect of lactacidosis on pyridine nucleotide stability during ischemia in mouse brain. 361 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>