Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear magnetic resonance (NMR) has contributed considerably to our understanding of experimental acute renal failure. Changes in energy metabolism which are caused by ischemia, urinary obstruction, and nephrotoxic drugs have been characterized with NMR spectroscopy. Data from our laboratory and others utilizing 31P NMR have demonstrated that levels of adenosine triphosphate fall rapidly with ischemia, and that the ability of the kidney to regenerate ATP correlates with ultimate functional recovery. Additionally, development of intracellular acidosis appears to occur early with ischemia and may, if severe enough, predict poor functional recovery. Urinary obstruction is associated with the rapid development of a large peak resonating in the phosphodiester region of the P-31 NMR kidney spectrum which is attributable to increases in urinary inorganic phosphate. Nephrotoxic acute renal failure with a variety of nephrotoxins is associated with little to no changes in high energy phosphates. Renal transplant allograft rejection is associated with energy metabolic changes similar to those seen with ischemia; however, the intracellular pH remains normal. These findings allow causes of experimental acute renal failure to be differentiated among each other in both native and transplanted kidneys. With recent advances in NMR software and hardware, the application of this methodology to human acute renal failure is now possible.
 ...
PMID:Contributions of nuclear magnetic resonance to study of acute renal failure. 269 84

Oxygen-derived free radicals have been implicated in the pathogenesis of cardiac dysfunction during ischemia, postischemic myocardial "stunning," and reperfusion injury. We investigated the effects of oxygen-derived free radicals on cardiac function in intact isolated rabbit hearts and single guinea pig ventricular myocytes. In the intact rabbit ventricle, exposure to free radical-generating systems caused increased cellular K+ efflux, shortening of the action potential duration, changes in tension, and depletion of high energy phosphates similar to ischemia and metabolic inhibition. In patch-clamped single ventricular myocytes, free radical-generating systems activated ATP-sensitive K+ channels, decreased the calcium current, and caused cell shortening by irreversibly inhibiting glycolytic and oxidative metabolism. The results suggest that free radicals generated during ischemia and reperfusion may contribute to electrophysiologic abnormalities and contractile dysfunction by inhibiting glycolysis and oxidative phosphorylation. Inhibition of metabolism by free radicals may be an important factor limiting functional recovery from an ischemic insult after reestablishment of effective blood flow.
 ...
PMID:Effects of exogenous free radicals on electromechanical function and metabolism in isolated rabbit and guinea pig ventricle. Implications for ischemia and reperfusion injury. 272 59

Quantitative Evaluation of Relationship between Cardiac Energy Metabolism and Post-ischemic Recovery of Contractile Function. Mechanisms of ischemic damage were studied by defining the relationships between post-ischemic work recovery and tissue ATP levels in isolated rat hearts as well as mitochondrial respiration rates in skinned myofibrils. Pre-ischemic levels of ATP were reduced by 2-deoxyglucose treatment and assessed using 31P-NMR. A 70% fall of ATP was not associated with decreased functional recovery. Mitochondrial respiration was assessed without mitochondrial isolation in skinned cardiac fibers in physiological salt solution using a novel method developed by Veksler et al. Maximal rates of mitochondrial respiration were not changed after 35 min of normothermic ischemia using St. Thomas's Hospital cardioplegic solution followed by 30 min of aerobic reperfusion. Only a reversible increase in the rate of basal respiration and a decrease in creatine-stimulated oxygen uptake were observed. Thus, mitochondrial oxidative phosphorylation, as assessed in skinned myofibrils, was tolerant to an ischemic period which induced permanent depression of contractile function along with alterations in metabolite distribution. As a result, tissue level of ATP and rates of mitochondrial respiration provided an estimate of ischemic damage only in cases where damage reached a very severe extent.
 ...
PMID:Quantitative evaluation of relationship between cardiac energy metabolism and post-ischemic recovery of contractile function. 273 31

Currently, for practical clinical purposes, the preservation of donor hearts is limited to about 4 h. Transplantation must be finished within this period to assure complete functional recovery upon reperfusion. From the clinical setting it is well known that hypothermia results in a better myocardial preservation during ischemia. During ischemia, rapid catabolism of high-energy phosphates (e.g., ATP and creatine phosphate) occurs. The purpose of this study was to investigate the influence of temperature during a 24-h preservation period on the rate of catabolism of ATP and on the rate of accumulation of breakdown products (ADP, AMP, adenosine, inosine, hypoxanthine, and xanthine). For this purpose, hearts were excised and stored for 24 h at 0.5 degrees, 12 degrees, or 18 degrees C. In addition, the effect of initial cardioplegic arrest was compared with simple normothermic excision of the heart followed by 24 h in cold storage. It was found that the higher the storage temperature, the higher the rate of catabolism of high-energy phosphates and, hence, after 24 h, the lower the final ATP level and the higher the level of breakdown products, mainly nucleosides. It was also found that the initial cardioplegic arrest strongly benefits the preservation of high-energy phosphates as a result of the ATP-sparing effect.
 ...
PMID:Optimal storage temperature and benefit of hypothermic cardioplegic arrest for long-term preservation of donor hearts: a study in the dog. 307 13

Fatty acids are known to increase the severity of injury during acute myocardial ischemia. In this study, we determined the effects of a carnitine palmitoyltransferase I inhibitor, ethyl 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate (Etomoxir) on reperfusion recovery of fatty acid perfused hearts. Following a 25-minute period of global ischemia, isolated working hearts reperfused with 1.2 mM palmitate, 11 mM glucose exhibited depressed function compared to hearts perfused with 11 mM glucose alone. A low dose of Etomoxir (10(-9) M) decreased long chain acylcarnitine and long chain acyl-coenzyme A (CoA) levels but did not prevent depressed function. In contrast, a high dose of Etomoxir (10(-6) M) prevented the palmitate-induced depression of function but did not decrease myocardial long chain acylcarnitine or long chain acyl-CoA levels. At this high dose of Etomoxir, oxygen consumption per unit work was decreased during reperfusion recovery, and ATP and creatine-phosphate levels were significantly higher after reperfusion. In aerobic hearts not subjected to ischemia, Etomoxir (10(-6) M) increased glucose oxidation both in the presence and absence of palmitate, while 10(-9) M Etomoxir had no effect. In these aerobic hearts, only the low dose of Etomoxir decreased long chain acylcarnitine and long chain acyl-CoA levels. These data demonstrate that Etomoxir (10(-6) M) increases functional recovery of fatty acid perfused ischemic hearts. This protection is unrelated to changes in levels of long chain acylcarnitines but may be due to increased glucose use by the reperfused heart, resulting in decreased oxygen consumption per unit work.
 ...
PMID:Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine. 319 71

The concentrations of renal ATP have been measured by 31P-nuclear magnetic resonance (NMR) before, during, and after bilateral renal artery occlusion. Using in vivo NMR, the initial postischemic recovery of ATP increased with the magnitude of the residual nucleotide pool at the end of ischemia. ATP levels after 120 min of reflow correlated with functional recovery at 24 h. In the present study the effect of blocking the degradation of ATP during ischemia upon the postischemic restoration of ATP was investigated. Inhibition of adenosine deaminase by 80% with the tight-binding inhibitor 2'-deoxycoformycin led to a 20% increase in the residual adenine nucleotide pool. This increased the ATP initial recovery after 45 min of ischemia from 52% (in controls) to 62% (in the treated animals), as compared to the basal levels. The inhibition also caused an accelerated postischemic restoration of cellular ATP so that at 120 min it was 83% in treated rats vs. 63% in untreated animals. There was a corresponding improvement in the functional recovery from the insult (increase of 33% in inulin clearance 24 h after the injury). Inhibition of adenosine deaminase during ischemia results in a injury similar to that seen after a shorter period of insult.
 ...
PMID:Metabolic and functional consequences of inhibiting adenosine deaminase during renal ischemia in rats. 326 96

The metabolic consequences of non-lethal complement-membrane attack in neutrophils have been investigated by the measurement of cellular ATP content and functional parameters, including chemotactic and phagocytic responses and the capacity to secrete reactive oxygen metabolites, in cells before and after attack. Immediately after non-lethal complement attack, cellular ATP content was reduced by more than 75%, although lactate dehydrogenase content was unaltered. Energy-requiring cell functions were similarly depressed. Incubation of cells in nutrient medium rapidly restored cell-energy stores and functions, demonstrating the completeness of recovery. Fluorescence-activated cell-sorter studies demonstrated that cells undergoing non-lethal complement attack underwent a reversible cell swelling, the cell diameter rapidly increasing from an average of 8.5 micron to 12 micron, then gradually shrinking back to a final average diameter of 8.2 micron. The results indicate that although non-lethal complement-membrane attack causes both metabolic and physical changes in neutrophils, these effects are transient and full functional recovery occurs.
 ...
PMID:Non-lethal complement-membrane attack on human neutrophils: transient cell swelling and metabolic depletion. 333 20

We tested the hypothesis that depletion of glycogen prior to myocardial ischemia diminishes lactate buildup and improves functional recovery on reperfusion in the isolated rabbit heart. Cardiac glycogen was reduced either by substituting N2 for O2 in the perfusate or by perfusion with substrate-free solution, before the onset of ischemia. Hearts were subjected to either 30 minutes of normothermic (37 degrees C) or 60 minutes of hypothermic (4 degrees C) ischemia followed by 30 minutes of reperfusion with oxygenated Krebs-Henseleit buffer. Function was assessed by measuring peak left ventricular pressure at end-diastolic pressures ranging from 0 to 20 mm Hg. N2 perfusion for 15 minutes lowered myocardial glycogen by 60% and decreased ATP and phosphocreatine (p less than 0.001). Glycogen depletion did not decrease lactate accumulation during ischemia, but it impaired recovery with reperfusion (-46%, p less than 0.05). N2 perfusion for 5 minutes also reduced glycogen by 60%, but energy-rich phosphates were not reduced and functional recovery was still impaired (-40%, p less than 0.05). Perfusion with substrate-free medium diminished glycogen by 33% (p less than 0.05). Although lactate accumulation was significantly reduced (-45%, p less than 0.05), recovery following reperfusion was not improved. The results suggest that preservation of glycogen stores, but not the prevention of lactate buildup during ischemia, is beneficial for the recovery of function with reperfusion.
 ...
PMID:Failure of glycogen depletion to improve left ventricular function of the rabbit heart after hypothermic ischemic arrest. 338 85

After relatively short periods of ischemia, reperfusion for several hours, or even days, is required to facilitate complete recovery of the ATP stores and mechanical function. The term "stunned" has been applied to these hearts. In the present experiments, isolated, spontaneously beating and electrically paced rat hearts were made ischemic for 10 min and then reperfused with Krebs-Henseleit buffer (KH) for up to 30 min. On reperfusion, functional recovery was impaired and the inotropic effect of Ca2+ blunted. In these experiments, the effect of a period of electrical and/or mechanical quiescence before the ischemic episode was investigated. Electrical quiescence was obtained by raising the KH K+ concentration, whereas mechanical without electrical quiescence was obtained by lowering the KH Ca2+ concentration or adding 2,3-butanedione monoxime (BDM). Mechanical arrest caused by low Ca2+ perfusion before ischemia failed to improve functional recovery on reperfusion. However, introducing a high K+ perfusate or BDM for a few minutes before ischemia significantly improved the recovery during reperfusion. This improvement was neither caused by energy preservation nor an altered "reflow area". The improvement may be caused by the increased osmolarity of KH containing high K+ or BDM, since adding 10 mM sucrose to KH for an equivalent time before ischemia improved recovery and abolished the blunted inotropic effect of Ca2+.
 ...
PMID:The stunned myocardium: effect of electrical and mechanical arrest and osmolarity. 339 26

Renal energy metabolism was investigated before, during, and after ischemic insults of varying durations with in vivo 31P NMR spectroscopy. The postischemic recovery of renal ATP was found to be a biphasic process regardless of the length of the ischemia. This two-stage recovery consisted of a quick initial component immediately upon reflow followed by a slower, more gradual return toward preischemic levels. To characterize the source of each phase of the recovery, kidneys were extracted with perchloric acid at the end of the different periods of ischemia (before reflow). Concentrations of adenine nucleotides and breakdown products adenosine, inosine, and hypoxanthine were determined by 1H NMR spectroscopy. Excellent correlation was found between the residual nucleotide pool and the magnitude of the initial phase of ATP recovery. Additionally, the renal ATP content after 120 min of reflow was shown to have a strong correlation with subsequent functional recovery. These experiments show that in vivo 31P NMR can provide new and dynamic information concerning the biochemical recovery from ischemia. Furthermore, this data has the potential to predict the eventual functional recovery of the organ.
 ...
PMID:Chemical and functional correlates of postischemic renal ATP levels. 346 81


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