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)

The changes in the contents of the main tricarboxylic acid cycle intermediates and related amino acids under total ischemia and subsequent reperfusion of isolated guinea pig heart were studied. The decrease in ATP and phosphocreatine during 30 min ischemia was accompanied by alanine formation and approximately stoichiometric glutamate loss. The increase in malate in ischemic myocardium corresponded to the anaplerotic flux aspartate----oxaloacetate----malate. The succinate production was commensurable to alpha-ketoglutarate formation in the alanine aminotransferase reaction. The release of bulk amount of lactate, alanine and succinate into the myocardial effluent was observed during an early phase of the reperfusion using 1H NMR. In contrast to these metabolites, malate release was not observed in the reperfusion. By the 30th min of the reperfusion the decrease in lactate, alanine, malate and succinate tissue contents to the preischemic values was accompanied by the recovery of ATP and phosphocreatine. The results suggest that the formation and the release of succinate and alanine from the heart, complementary to that of lactate, reflect profound disturbances in energy metabolism.
 ...
PMID:Metabolism of the tricarboxylic acid cycle intermediates and related amino acids in ischemic guinea pig heart. 289 8

The effects of total ischemia and subsequent reperfusion on the formation of anaerobic metabolism products and their release into myocardial effluent were studied in isolated guinea pig hearts. During 30-min ischemia myocardial ATP and phosphocreatine decreased to 34 and 15% of the initial levels, respectively; this was accompanied by alanine formation and approximately stoichiometric glutamate loss. The increase in malate in ischemic myocardium corresponded to the anaplerotic flux aspartate----oxaloacetate----malate; the succinate production being commensurable to alpha-ketoglutarate formation in the alanine aminotransferase reaction. The release of lactate, alanine, succinate, creatine and pyruvate trace amounts into the myocardial effluent was observed during an early phase of the reperfusion using 1H-NMR. The rates of metabolite release reduced as follows: lactate much greater than alanine greater than succinate greater than creatine. By the 30th min of the reperfusion the decrease in these metabolites tissue contents was accompanied by the recovery of ATP and phosphocreatine levels up to 65 and 90% of the initial ones, respectively. The data obtained demonstrate that the formation and the release of succinate, alanine and creatine from the heart as well as of lactate may indicate profound disturbances in energy metabolism.
 ...
PMID:An assessment of anaerobic metabolism during ischemia and reperfusion in isolated guinea pig heart. 337 59

The effect of ischemia on the formation of products of anaerobic metabolism and their release into the cardiac effluent in isolated perfused guinea pig hearts was studied. During 30 min normothermal ischemia, the myocardial ATP and phosphocreatine levels decreased to 34% and 15% of the initial values, respectively. The net alanine formation in ischemia was approximately a stoichiometric glutamate decrease; the increase in the tissue malate content corresponded to the aspartate----oxaloacetate----malate anaplerotic flux, the succinate production being commensurable to alpha-ketoglutaric acid formation in the alanine aminotransferase reaction. Using 1H-NMR, it was shown that the release of trace amounts of lactate, alanine, succinate, creatine and pyruvate into cardiac effluents occurred during the first 5 minutes of reperfusion. The rate of metabolite release decreased in the following order: lactate much greater than alanine greater than succinate greater than creatine. By the 30th minute of reperfusion, the decrease in the tissue levels of these metabolites to preischemic values was accompanied by the recovery of ATP and phosphocreatine to 65% and 90% of the initial levels, respectively. The data obtained suggest that the formation and release of alanine, creatine or succinate as well as lactate from ischemic myocardium may testify to significant disturbances in energy metabolism of the myocardium.
 ...
PMID:[Formation of products of anaerobic metabolism in the ischemic myocardium]. 337 64

The changes of hepatic energy metabolism during normothermic and hypothermic ischemia were investigated using rats with portajugular shunt. In addition, some blood parameters were estimated as to whether they could reflect the changes in hepatic energy level (represented by energy charge, EC). In this study, [pyruvate]/[lactate] x 1/K(K = 1.11 x 10(-4)) and [2-oxoglutarate] x [ammonia]/[glutamate] x 1/K(K = 3.87 x 10(-3) mmole) were used as indexes of cytosolic and mitochondrial redox state, respectively. The following results were obtained. 1) Though hepatic EC recovered after 30 minutes of ischemia, it didn't recover after 60 minutes of normothermic ischemia. 2) The recovery of the hepatic EC even after 60 minutes of ischemia was observed in hypothermic condition. 3) Mitochondrial redox state changed like hepatic EC, however, some dissociations were observed between cytosolic redox state and hepatic EC in hypothermic ischemia. 4) The changes of mitochondrial and cytosolic redox state were reflected in those of arterial ammonia and lactate level, respectively. As a result, hypothermia can prolong the safe ischemic period due to its stabilizing effect on mitochondrial redox state. In addition, the changes of the hepatic EC are reflected in those of arterial ammonia and lactate level. In hypothermic condition, however, ammonia seemed a better parameter than lactate in assessing hepatic EC.
 ...
PMID:[Study of the ischemic effect on the hepatic energy metabolism]. 341 4

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

Both phases of the calcium paradox were associated with major alterations in myocardial energy metabolism. During calcium-free perfusion contractility of the heart ceased, resulting in a dramatic decrease in anaerobic and aerobic metabolism but no change in tissue high energy phosphate levels. Tissue content of most citric acid cycle intermediates were elevated, while there was a net decrease in the content of transaminase-linked amino acids. Reperfusion of the calcium-depleted heart with calcium-containing buffer failed to restore either the contractile or the metabolic state of the heart. Within seconds following calcium repletion, tissue high energy phosphate content plummeted. This occurred even though glucose utilization increased significantly and aerobic metabolism remained at levels observed in the calcium-depleted heart. Analogous to changes seen in acidosis and ischemia, alpha-ketoglutarate and citrate levels decreased abruptly. After a short delay, the levels of several key amino acids also dropped. The results support the hypothesis that the impairment of mitochondrial function contributes to the depletion of high energy phosphate stores during the calcium paradox.
 ...
PMID:Effect of calcium depletion and calcium paradox on myocardial energy metabolism. 407 57

To investigate the effects of ischemia on renal metabolites, sequential slices of renal cortex were removed during 5 min of renal artery occlusion and for 5 min after release of occlusion. ATP concentrations rapidly fell during ischemia and rose during the postischemic period. Based on the rate of decline of ATP concentrations, the rate of ATP production was estimated to be 0.5 mumol ATP/g/min. This is considerably less than the rate of ATP production estimated from renal O2 consumption. During ischemia, AMP concentrations rose, confirming the activity of adenylate kinase. The control lactate/pyruvate ratio suggested that dog kidney cytosol is more reduced than the cytosol of rat liver and kidney. During ischemia, the lactate concentrations and the lactate/pyruvate ratio of dog renal cortex increased as expected, and fell after restoration of blood flow. beta-Hydroxybutyrate concentrations are considerably lower than those previously reported for rat liver and kidney. The beta-hydroxybutyrate/acetoacetate ratio was not measurable during ischemia. However, the mitochondrial redox state, calculated from the glutamate/alpha-ketoglutarate . NH+4 ratio, was similar to previous reports and this ratio appropriately changed during the ischemic and post-ischemic period.
 ...
PMID:Effects of ischemia on metabolite concentrations in dog renal cortex. 612 3

Glutamic acid may protect the ischemic myocardium by increasing the flux through anaerobic pathways for ATP production. We tested this in isolated rabbit hearts that were treated with 0 or 2 mM glutamate. Hearts were stabilized for 30 min, subjected to ischemia for 30 min, and then reperfused for 30 min. Cardiac performance was defined by measuring peak left ventricular pressure (PLVDP) at the apex of a Starling curve and expressed as the %PLVDP attained during the preischemia period. Glutamate improved cardiac performance (%PLVDP, treated vs. untreated) after moderate ischemia (92 vs. 67), severe ischemia (79 vs. 65), and total ischemia (61 vs. 41). During severe ischemia, improved performance was associated with enhanced release (nmol X g wet wt -1 X min -1, treated vs. untreated) of alpha-ketoglutarate (2.3 vs. 1.3), succinate (21.7 vs. 12.3), and lactate (478 vs. 386). The ischemic myocardial content (nmol/mg myocardial protein, treated vs. untreated) of alpha-ketoglutarate (1.7 vs. 1.2) was increased by glutamate. The ischemic content of ATP (25.4 vs. 21.9) and succinate (15.7 vs. 12.1) showed a slight trend toward improvement under glutamate treatment. The study shows an association between improved postischemic cardiac performance and increased production of alpha-ketoglutarate and succinate during glutamate treatment.
 ...
PMID:Protection of ischemic rabbit myocardium by glutamic acid. 613 48

The most important biochemical derangements in ischemic myocardium are the decrease of energy rich phosphates (ATP and phosphocreatine) and intracellular acidosis, both of which contribute to a rapid loss of the contractile function. How and to which extent the alterations of carbohydrate and lipid metabolism are involved in these derangements is briefly discussed. In conditions of oxygen restriction the synchronism between the cytosolic and mitochondrial phase of carbohydrate metabolism is disrupted and beta-oxidation of long chain fatty acids is prevented. Consequently less ATP and more lactate is produced and fatty acids accumulate together with their activation products, acyl CoA in particular. In ischemia free carnitine is also decreased and the carnitine dependent functions (acyl transfer across mitochondrial membrane and pyruvate and alpha ketoglutarate dehydrogenase stimulation) impaired. The meaning of the altered carnitine dependent functions is considered together with the possible (demonstrated and supposed) metabolic effects of carnitine administration in cardiac ischemia.
 ...
PMID:Biochemical derangements in ischemic myocardium: the role of carnitine. 624 Apr 23

Glycolytic substrates and metabolites (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate), tricarboxylic acid cycle intermediates (citrate, alpha-ketoglutarate, succinate, fumarate, malate), related amino acids (glutamate, glutamine, alanine, gamma-aminobutyrate) and energy mediators (ATP, ADP, AMP, creatine phosphate) were evaluated in the cerebral cortex of rats after 5 min of complete compression ischemia as well as after 3, 15 or 30 min of recirculation following 5 min ischemia. The post-ischemic recovery was studied in control animals or in animals treated (30 min before ischemia and during discovery) by intravenous perfusion of vincamine, theophylline, dihydroergocristine and alanine. Interrelated changes of intermediates of the carbohydrate and the amino acid metabolism have been observed. It is concluded that alanine perfusion induced a partial detour of the lactacid anaerobic process towards the succinate-related alactacid cycle, leading to an increase in the cortical gamma-aminobutyrate content. Vincamine and dihydroergocristine acted in the opposite direction.
 ...
PMID:Drug interference on some biochemical parameters of rat cerebral cortex during post-ischemic recovery. 677 99


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