Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392674 (exhaustion)
 13,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During aortic clamping, drug protection of the myocardium, far from supplanting hypothermia, complements it, particularly in the case of left ventricular hypertrophy. Ultramicroscopy and new techniques of histobiological exploration of the myocite have enabled one to distinguish the lessions provoked by anoxia from those induced by reperfusion. At present, drug protection, extended to energetic solutions and electrolytes, aim at preserving energy metabolism by stocking of the substrate and at avoiding interferences which precipitate exhaustion of the adenosine triphosphate and phosphocreatinine reserves. In order to do this, hemodilution in particular is limited in subjects with decompensated cardiopathy; choice of anesthetics is orientated towards neuroleptanalgesia or fluothane, and it is attempted to neutralize the adrenergic reaction by the use of beta-blocking substances. Furthermore, it is preferred to interrupt electrogenesis at the stage of polarization: depolarizing cardioplegic solutions rich in potassium and sodium are rejected and in preference membrane stabilizers are used (procaine, magnesium, tetrodoxine...) The ultramicroscopic analysis of the structural modifications leads to sparing of the integrity of the lysosomial membrane by corticoids and alkalines. The use of calcium is deferred, anti-calcium techniques are even proposed (washing poor in calcium, verapamil). Cellular edema is prevented and treated by solution (mannitol - sorbitol) whose osmolarity must be less than 300 M osm/l. A conditioning of the biochemical and physicial structures and of cardiac work is being more and more thought of which leads to the classification of beta stimulating substances as negative, and their indications must be seriously thought of and used with reserve.
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PMID:[Drug protection of the myocardium during cardiac surgery]. 1 31

1. Formycin triphosphate (FTP), a fluorescent analogue of ATP, is a substrate for (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3), with properties similar to those of ATP. 2. FTP and formycin diphosphate (FDP) bind to the enzyme with high affinity and, on binding, the nucleotide fluorescence is enhanced 3-4-fold. It is therefore possible, with a stopped-flow fluorimeter, to measure the rates of binding and release of FTP and FDP under conditions in which turnover does not occur. 3. When the enzyme-FTP complex is exposed to conditions permitting turnover (Mg2+, Na+ +/- K+), changes in fluorescence occur which can be explained by supposing that they reflect the interconversion of states with or without bound nucleotides. A rapid fall in fluorescence, that we attribute to the rapid release of FDP from newly phosphorylated enzyme, is followed by a steady state in which low fluorescence suggests that little nucleotide is bound. Eventually, exhaustion of FTP allows rebinding of FDP to the enzyme, which is signalled by a rise in fluorescence. 4. The estimated rate of FDP release from newly formed phosphoenzyme is unaffected by the presence of K+ (0-2 mM) or the concentration of FTP (1-20 micron). 5. Experiments with [gamma-32P]FTP show that about 1 mol of 32P is incorporated per mol of enzyme. The rate of phosphorylation of the enzyme by [gamma-32P]FTP has been measured with a rapid-mixing-and-quenching apparatus. 6. Kinetic data from the fluorescence and phosphorylation experiments show that the behaviour of the enzyme, at least at the low nucleotide concentrations employed, is consistent with the Albers-Post model, and is difficult to reconcile with models in which K+ acts at or before the step in which FDP is released during turnover.
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PMID:Elementary steps of the (Na+ + K+)-ATPase mechanism, studied with formycin nucleotides. 21 Aug 11

We prospectively studied the clinical, biochemical (including creatine phosphokinase (CPK) isoenzymes) and electrocardiographic features of exertional heat stroke in 13 patients (group 1) and severe heat exhaustion in 14 patients (group 2). Despite initial presentations with severe hyperthermia, tachycardia and hypotension, only one patient with heat stroke had myocardial ischemia. The CPK isoenzymes were not indicative of myocardial damage in any patient. The patients with heat stroke were somewhat more dehydrated than those with heat exhaustion as measured by differences in serum creatinine, sodium and osmolality, and the former (group 1) had a significantly lower initial glucose level (P less than 0.05). Although significant differences in potassium were not observed in the pretreatment samples, at 12 hours the serum potassium was significantly lower in group 1 (P less than 0.05). This suggests that this group may have been more potassium-depleted at the time of heat stroke. Prompt recognition and vigorous therapy were successful in rapidly lowering high temperatures and in preventing serious complications.
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PMID:Cardiovascular and metabolic manifestations of heat stroke and severe heat exhaustion. 42 71

Blood samples were taken from 15 horses before and after a 50-mile ride to examine the changes occurring in some biochemical constituents. There was a significant (P less than 0.05) decrease in plasma potassium, calcium and magnesium concentrations and a rise in inorganic phosphate but there was no alteration in plasma sodium, chloride or protein levels or change in haematocrit. After the ride there was a highly significant (P less than 0.01) fall in blood glucose corresponding with increased lipolysis and a rise in plasma free fatty acids (P less than 0.001) and glycerol (P less than 0.001). There was a modest increase in blood lactate and a rise in plasma creatine phosphokinase. The results of this preliminary investigation are discussed in relation to the problem of exhaustion in horses during endurance rides.
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PMID:Biochemical changes in horses during a 50-mile endurance ride. 65 49

To evaluate the roles of circulating hydrogen ion and lactate in the production of exercise-induced asthma, two experiments were performed. In the first, we exercised six asthmatic subjects to exhaustion on a bicycle ergometer while recording arterial pH at periodic intervals. Multiple aspects of pulmonary mechanics were measured before and after the work load. After recovery, the identical procedures were repeated, but sufficient quantities of sodium bicarbonate were infused to keep the pH at the pre-exercise level. In both experiments, statistically identical attacks of asthma were induced. To study the effect of lactate, five subjects were exercised on several occasions in order to determine the lowest level of work, and hence arterial lactate, that was reproducibly associated with an acute asthma attack. When this was known, sufficient quantities of sodium lactate were infused into the resting subjects so as to equal or exceed the amount produced with exercise. Pulmonary mechanics were not altered with this intervention. These findings demonstrate that lactic acidemia is not the cause of exercise-induced asthma.
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PMID:A critical assessment of the roles of circulating hydrogen ion and lactate in the production of exercise-induced asthma. 89 69

1. The mechanisms responsible for the depolarization of the hepatocytes secondary to anoxia have been studied in isolated perfused dog liver. It was attempted to elucidate the role of the inhibition of the sodium pump following exhaustion of the energy reserves and of the modifications of membrane permeability. Anoxia was compared to ouabain and to a reduction of the cellular ATP level. 2. Membrane potentials were measured with micro-electrodes. Potassium, sodium and chloride were determined in plasma samples and liver tissues. Extracellular space was measured with tritiated inulin or with an electrical impedance method. Adenine nucleotides were also measured in liver biopsies. 3. The fall in membrane potential produced by administration of ouabain (0-1 mM) is greater than the effect of the redistribution of sodium + potassium ions; this suggests that the sodium pump is functioning, at least partially, electrogenically. The administration of dinitrophenol (10 mM), which causes a 74% fall in the ATP level in 15 min, produces, as does ouabain, a depolarization which also corresponds to stopping an electrogenic pump. 4. A partial reduction in the level of ATP brought about by hypoxia, by an inhibitor of cellular respiration, antimycin (10 mM), or by fructose (20 mM) results in a hyperpolarization which may be attributed to an elevation of potassium permeability (PK) since it is concomitant to a loss of K from the liver. The change in membrane permeability could be related to a rise in the free calcium in the cells which has not been documented. Other possible hypothesis include a facilitated transport for potassium. 5. The administration of amobarbitone (10 mM) produces immediately a depolarization which is independent of the progressive reduction in the level of ATP. The depolarization has been attributed to a direct effect of amobarbitone on the membrane reducing the permeability for potassium ions. 6. The depolarization observed in ischaemic anoxia is greater than that produced by ouabain for the same variation in ions concentration. In addition to a likely inhibition of the electrogenic sodium pump, changes in membrane permeability inducing a rise in the PNa/PK ratio must also occur. 7. After ischaemic anoxia for 24 hr at 3 degrees C, the ratio of PNa/PK rises to 0-68 which indicates abolishment of the selective character of membrane permeability. The augmentation in cell volume produced by anoxia might result in an opening of membrane pores, which could entail the augmentation of sodium permeability; the latter would be responsible in part for the depolarization produced by anoxia. 8. According to the severity and length of oxygen deprivation an increase in PK, a cessation of the sodium pump activity and finally an increase in PNa will occur.
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PMID:Effect of anoxia and ATP depletion on the membrane potential and permeability of dog liver. 89 69

1. The membrane characteristics of metabolically poisoned and mechanically exhausted frog skeletal muscle fibres were investigated with intracellular micro-electrodes. 2. When cyanide plus iodoacetate were applied as metabolic poisons twitch tension declined towards zero after 150-300 stimuli (0-3 Hz; temperature = 0 degrees C). At the beginning of stimulation the mean resting potenial fell from -75 to -69 mV; it rose subsequently to -83 mV. The membrane resistance decreased during this stimulation period along a sigmoid time course to 4-6% of the original value. 3. In completely exhausted fibres the following membrane constants were estimated (23 degrees C): length constant, 0-31 mm; input resistance, 31 komega; membrane resistance, 58 omega.cm2. These values were calculated under the assumption of a constant internal resistivity of 170 omega. cm. The Q10 values of these constants were similar to those in normal fibres. Afew experiments revealed that the membrane capacity remained roughly constant under these conditions. 4. The current-voltage relation of exhausted fibres was approximately linear in the range between -60 and -100 mV. At less negative potentials the conductance increased slightly while at more negative potentials it decreased. The latter, in particular, became more evident when the imput current was converted into membrane current density by applying Cole's theorem. 5TEA+ and Rb+ in the external solution increased the membrane resistance of exhausted fibres by more than one order of magnitude. The major part of the membrane conductance induced by exhaustion, however, could not be blocked by these ions or Zn2+. 6. Chloride-free test solutions were used to measure the relative contributions of potassium and chloride ions to the membrane conductance. The relation GK:GC1 changed from 2:3 in normal fibres to 5:1 in exhausted ones. In absolute terms GK rose from ca. 130 to 14,300 mumho/cm2 and GC1 from ca. 200 to 2900 mumho/cm2. The discrimination between K+ and Na+ by the resting membrane in exhausted fibres was probably equal to or even higher than that under normal conditions. 7. In normal fibres the input resistance decreased by up to 20% after the external application of 1-2 mM caffeine, which is known to release calcium ions from internal stores. The elevation in internal Ca2+ by direct injection caused a small and, as a rule, irreversible decrease in input resistance which was probably partly due to local damage to the surface membrane. 8. It is concluded that in metabolically exhausted muscle fibres the surface and tubular membranes are still intact and that the observed decrease in membrane resistance is mainly due to an increase in potassium conductance. In addition, the results indicate that the gating mechanism of the potassium channels (presumably those with the characteristics of the slow component) is affected when energy reserves diminish.
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PMID:An evaluation of the membrane constants and the potassium conductance in metabolically exhausted muscle fibres. 108 32

The toxicity of FUT-187, a synthetic protease inhibitor, was investigated in Sprague-Dawley rats. FUT-187 was given orally to the rats at doses of 2, 10, 50, 250 and 1250 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks for recovery. The results are summarized as follows: In the 1250 mg/kg/day group, 9 out of 20 males died with decreased body weight and exhaustion. Histopathological examination revealed renal papillary necrosis, ulcer in the urinary bladder, hemostatic lesions in the lungs and liver, ulcer or erosion in the stomach, duodenum and jejunum. The surviving animals in this group showed swelling of the limbs due to synovitis, transient salivation immediately after administration, suppression of growth with decreased food consumption. Urinalysis revealed a low pH, increased ketones and bilirubin excretion, dark yellowish change in color, the appearance of "leaflet-shaped" crystals and increased red blood cells and epithelial cells in the urinary sediment, increased water intake, decreased specific gravity and decreased sodium, potassium and chloride in the urine. Hematologically, there was an increase in the white blood cell count. A biochemical analysis of the blood revealed decreased amylase activity, glucose and total protein levels and increased GOT activity and inorganic phosphorus levels. Pathological changes were observed in the pancreas, kidney, digestive tract, urinary bladder and liver. The pancreas showed macroscopical enlargement and increased organ weight. Histopathologically, there were several alterations in the acinar cells, such as vacuolization due to increased fat droplets, nuclear irregularity, prominent nucleoli, irregular arrangement and vesiculation of rough endoplasmic reticulum (rER), dilatation of developed Golgi apparatus and increased free ribosomes. In the kidney, increased weight and pigmentation in the proximal tubular epithelium were noted. Electron microscopically, these pigments were recognized as secondary lysosomes containing filamentous material and electron dense granules within a lucent matrix. In the digestive tract, ulcer or erosion in the stomach and duodenum, and villous proliferation in the small intestine were observed. Furthermore, hyperplasia and vacuolization were noted in the mucosal epithelium of the urinary bladder. In addition, loss of perilobular fat droplets in the liver and increased adrenal weight without histological change were observed. After a 5-week recovery period, these changes disappeared almost completely. In the 250 mg/kg/day group, slight suppression of growth the appearance of "leaflet-shaped" crystals in the urinary , sediment, increased water intake and decreased sodium in the urine were observed. The pancreas showed enlargement, increased weight, acinar cell hypertrophy with increased zymogen granules, fine vacuolization, slight derangement and vesicular of rER, and dilatation of Golgi apparatus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A 13-week subacute oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187) in rats]. 129 23

Red cell membranes were isolated from blood samples obtained from athletes during exhaustive exercise on a bicycle ergometer and during the subsequent recovery period of 60 min. Plasma lactate levels were also determined. During exercise, cell membranes were progressively depleted of cholesterol and, at exhaustion, membrane cholesterol was less than 80% of the initial level. A parallel decline in Na+,K(+)-ATPase was also noted, while phospholipid reduction was around 5%. During recovery, the erythrocyte membrane cholesterol and Na+,K(+)-ATPase increased, but at a slow rate and were inversely proportional to plasma lactate content.
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PMID:Exercise-induced cholesterol depletion and Na+,K(+)-ATPase activities in human red cell membrane. 133 61

The influence of moderate cold exposure on the hormonal responses of atrial natriuretic factor (ANF), arginine vasopressin (AVP), catecholamines, and plasma renin activity (PRA) after exhaustive exercise was studied in 9 young and 10 middle-aged subjects. Exercise tests were randomly performed in temperate (30 degrees C) and cold (10 degrees C) environments. Heart rate, oxygen consumption, and peripheral arterial blood pressure were measured at regular intervals. Blood samples were collected before and immediately after exercise at 30 or 10 degrees C. Plasma sodium and potassium concentrations as well as hemoglobin and hematocrit were measured, and the change in plasma volume was calculated. At rest and during exercise, oxygen consumption was similar during exposure to both temperate and cold temperatures. During submaximal exercise intensities, the rise in heart rate was blunted while the increase in systolic blood pressure was significantly greater at 10 than at 30 degrees C. The increases in plasma sodium and potassium concentrations after exhaustion were similar between environments, as was the decrease in plasma volume. In both groups, all plasma hormones were significantly elevated postexercise, with the AVP response similar at 10 and 30 degrees C. However, the norepinephrine and ANF responses were significantly greater while the PRA response was significantly reduced at 10 degrees C. In the middle-aged subjects the epinephrine response to exercise was higher at 10 than at 30 degrees C. The greater ANF and reduced PRA responses to exercise in the cold may have resulted from central hemodynamic changes caused by cold-induced cutaneous vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal responses to exercise during moderate cold exposure in young vs. middle-age subjects. 144 5


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