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

The first application of human in vivo phosphorus (31P) magnetic resonance spectroscopy to analysis of skin metabolism is presented. Our results confirm that phosphocreatine is a major energy phosphometabolite in human skin. Human in vivo 31P spectroscopy utilizing a skin coil designed in our laboratory can have clinical applications in cutaneous surgery and clinical dermatology, and will facilitate understanding of the pathophysiology of skin disease. In vitro experiments with fresh human skin indicate that complete utilization of phosphocreatine is followed by utilization of adenosine triphosphate (ATP) molecules during ischemia. These experiments also suggest that the majority of phosphocreatine in human skin is localized in epidermal and papillary dermis.
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PMID:Human in vivo 31P spectroscopy of skin: potentially a powerful tool for noninvasive study of metabolism in a cutaneous tissue. 280 89

The biochemical effects of peripheral vascular disease on skeletal muscle have not been characterized precisely because of the lack of satisfactory noninvasive analytic methods. 31P nuclear magnetic resonance (NMR) spectroscopy was used to measure the high-energy phosphate compounds, phosphocreatine (PCr) and adenosine triphosphate, as well as metabolic byproducts, such as inorganic phosphates (Pi) and phosphate monoesters in calf muscles of 214 limbs with peripheral vascular disease. Intracellular pH was also measured. The NMR index (Pi[PCr + Pi]) was used to quantitate the impairment of oxidative phosphorylation as a result of ischemia. Studies done at rest documented the impairment of oxidative metabolism only in limbs with severe ischemia (ankle-brachial pressure index (API) less than 0.4). Exercise resulted in a significant elevation of the NMR index in all limbs and the rate of return of this value toward normal following exercise was prolonged even in limbs with moderate ischemia (0.4 less than or equal to API less than or equal to 0.9). Correlation of 31P NMR parameters with arteriograms showed that infrapopliteal occlusions resulted in prolonged recovery times only when the superficial femoral artery was occluded and emphasized the metabolic consequences of multisegmental disease. Accumulation of glycolytic pathway intermediates correlated with the decrease in muscle cell pH observed with exercise. Despite immediate improvement in symptoms and hemodynamic parameters following revascularization, return to normal biochemical function occurs over a prolonged period of time. This study demonstrates that 31P NMR spectroscopy can successfully measure noninvasively the important phosphorus-containing compounds involved in the bioenergetics of skeletal muscle in vivo rapidly enough to permit real-time determination during exercise and recovery.
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PMID:31P nuclear magnetic resonance spectroscopy: noninvasive biochemical analysis of the ischemic extremity. 293 3

Lens repair and calcification have been studied in an experimental rabbit model of anterior segment necrosis. Findings were compared with those in a human senile cataractous lens with subcapsular calcification. Rabbit lenses subjected to anterior segment ischemia underwent a repair process similar to that observed in perforating lens injuries. Cellular response included the formation of fibroblast-like cells that covered epithelial defects of the anterior pole. These observations suggest that the lens epithelium can transform into fibroblast-like cells. The calcification process was a non-cell-induced, and the observed mineral was probably nucleating on organic molecules. Elemental analysis demonstrated that crystals contained calcium and phosphorus with a ratio of 2:1. The mineral was probably hydroxyapatite. Since morphological findings in rabbit lenses closely resemble those of the studied cataractous human lens, the rabbit model appears to simulate one type of lens calcification in senile cataract.
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PMID:Human and experimental lens repair and calcification. 302 47

Gated acquisition of 19F nuclear magnetic resonance spectra from perfused ferret hearts loaded with the fluorinated Ca2+ indicator 5,5'-F2-BAPTA allows direct quantitation of the cyclical changes in the intracellular free Ca2+ concentration ([Ca2+]i) that underlie contraction in intact hearts. [Ca2+]i increased from approximately 200 nM in diastole to approximately 1 microM or higher in early systole. Although the 19F spectra that report [Ca2+]i changed dramatically and reproducibly during the cardiac cycle, no changes were detectable in gated phosphorus spectra. We exploited the ability to control the coronary arterial flow of our hearts to investigate the mechanism of the fall in contractility that results from a decrease in perfusion even when the flow suffices to sustain normal high energy phosphate concentrations. Under these conditions, the amplitude of Ca2+ transients falls markedly along with the decline in pressure. This down-regulation of Ca2+ transients constitutes a novel protective mechanism that minimizes energy demand during low-flow ischemia.
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PMID:Ca2+ transients in perfused hearts revealed by gated 19F NMR spectroscopy. 313 52

The significance of dynamic changes in energy state during lung harvesting and preservation has not been extensively studied. Phosphorus 31 nuclear magnetic resonance spectra at 81 MHz were obtained from degassed rabbit lungs. Changes in the adenosine 5'-triphosphate-to-inorganic phosphate peak-intensity ratios were used to measure changes in energy state. Two groups of rabbit preparations were studied to evaluate the effect of hypothermia during the initial 120 minutes of harvesting (n = 8 at 36 degrees C and n = 5 at 4 degrees C). The significance of these changes was assessed in a second experiment in which lungs were reperfused in vitro at selected intervals of hypothermia (5, 12, and 24 hours) and assessed for injury. Hypothermic preservation sustained a significantly higher energy state. The depletion of energy state was correlated with injury, particularly as measured by lung edema (r2 = -0.715). Short periods of warm ischemia (30 minutes) result in a significant depletion of energy state, which may be a component of pulmonary injury during harvesting and preservation.
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PMID:31P nuclear magnetic resonance determination of changes in energy state in lung preservation. 318 Apr 8

In 27 cats treated to vary arterial serum glucose concentrations, we measured cerebral high-energy phosphate metabolite concentration and intracellular pH using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy during transient global cerebral ischemia and reperfusion. Hypoglycemia was induced with 4 units/kg i.v. insulin in six cats before ischemia; hyperglycemia was induced with 1.5 g/kg i.v. glucose in six cats before and in six cats during ischemia. Nine untreated cats subjected to ischemia without manipulation of blood glucose concentration served as controls. During ischemia, intracellular pH fell to similar levels in the control and both hyperglycemic groups. During reperfusion, the hyperglycemic before ischemia group initially exhibited a severe further decline in intracellular pH (p less than 0.003); this further decline was not observed in the control or the hyperglycemic during ischemia groups. Intracellular acidosis was attenuated both during ischemia and early after reperfusion in the hypoglycemic before ischemia group. In all groups, cerebral high-energy phosphate metabolite concentrations were depleted during ischemia and then recovered to the same degree during reperfusion. Our data suggest that brain glucose stores before ischemia determine the severity and time course of intracellular acidosis during ischemia and reperfusion.
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PMID:Global cerebral ischemia and intracellular pH during hyperglycemia and hypoglycemia in cats. 318 23

Of all tissues of the extremities, muscle is the least tolerant of ischemia. Hypothermia of tissue is considered beneficial for the maintenance of viability of muscle in amputated limbs before surgical replantation, but it has never been established that conventional cooling in an ice bath or its equivalent (temperature of tissue, approximately 1 degree Celsius) is the optimum level of hypothermia for minimizing metabolic derangement in ischemic muscle. In this study, we first defined the time course and level of metabolic derangement of muscle in twenty-eight ischemic hind limbs in cats at 22, 15, 10, 5, and 1 degree Celsius. The levels of adenosine triphosphate and phosphocreatine and the mean intracellular pH of the muscles in the lateral aspect of the thigh in each limb were monitored with phosphorus nuclear magnetic-resonance spectroscopy over time. The excised muscles from six freshly amputated legs of live humans were then similarly studied to determine whether muscles from cats and from humans exhibit comparable bioenergetic responses to hypothermic ischemia. A final series of ten ischemic hind limbs from cats was studied by nuclear magnetic resonance and muscle biopsy for direct biochemical assay of tissue energy metabolites to compare the metabolic benefits of two different methods of preserving limbs: continuous cooling in an ice bath, and a newly devised protocol for the rapid induction and maintenance of so-called intermediate (10 +/- 5 degrees Celsius) hypothermia of tissue. Ischemic skeletal muscle in cats exhibited a paradoxical metabolic response to extreme cold (1 degree Celsius). The rate of metabolic deterioration progressively declined with decreasing temperature of tissue to 10 degrees Celsius. However, at 5 degrees Celsius, no additional benefit was detected, and at 1 degree Celsius, there was a significant acceleration in the rates of degradation of adenosine triphosphate and phosphocreatine and in the production of lactate. The rate of degradation of adenosine triphosphate in human ischemic muscle was also faster at 1 degree Celsius than at 10 degrees Celsius. This paradoxical response is apparently due to a severe inhibition of the calcium pump of the sarcoplasmic reticulum of the muscle cell at temperatures of less than 5 degrees Celsius. The inhibition permits an efflux of calcium to the myofibrils, which stimulates both glycolysis and the degradation of adenosine triphosphate by myofibrillar adenosine triphosphatase.
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PMID:The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia. 319 76

We investigated the effect of mild whole-body hyperthermia before and after 16 minutes of global cerebral ischemia on metabolic recovery during recirculation in cats using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy. Hyperthermia (temperature 40.6 +/- 0.2 degrees C) was induced greater than or equal to 1 hour before ischemia and was maintained during 1.5-2 hours of recirculation in nine cats; four cats were subjected to hyperthermia without cerebral ischemia, six to hyperthermia during recirculation (after return of intracellular pH to preischemic values), and 14 to normothermic ischemia and recirculation. Our data indicate that preischemic hyperthermia results in an intracellular cerebral pH during recirculation significantly lower than that in normothermic cats. In hyperthermic cats beta-ATP and phosphocreatine (PCr) concentrations and the ratio of PCr to inorganic phosphate failed to return to preischemic levels during recirculation in contrast to normothermic cats. Hyperthermia without ischemia and hyperthermia during recirculation had no significant effect on intracellular pH. Thus, preischemic hyperthermia has a detrimental effect on metabolic recovery after transient global cerebral ischemia.
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PMID:Effect of mild hyperthermia on recovery of metabolic function after global cerebral ischemia in cats. 320 11

Protective effects of verapamil on dynamics of phosphorus-containing metabolites were studied during 30 min complete ischemia by means of 31P NMR. Verapamil appears to decrease the ATP and creatine phosphate pools consumption in ischemic brain tissue. The efficiency of the drug depended on the administration procedure and was not similar in two different models of ischemia. Possible mechanisms of the verapamil effect on bioenergetics of nervous tissue are discussed.
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PMID:[The effect of verapamil on the dynamics of decrease in the brain levels of phosphorus macroergs during ischemia studied by 31P-NMR in vivo]. 323 32

The effects of 11.7 mM glucose, insulin, and potassium (GIK) on metabolism during ischemia were investigated in the perfused guinea pig heart using magnetic resonance spectroscopy. Intracellular metabolites, primarily glycogen and glutamate, were labeled with 13C by addition of [1-13C]glucose to the perfusate during a normoxic, preischemic period. 13C and 31P NMR spectroscopy was used to observe the metabolism of 13C-labeled metabolites simultaneously with high-energy phosphorus metabolites and pH. The extent of acidosis and the rate and amount of labeled lactate accumulation during ischemia were the same in control (3 mM glucose + insulin) and GIK-treated hearts. In contrast, the rate of labeled glycogen mobilization during ischemia in GIK-treated hearts was one third the rate observed in control hearts. These observations suggest that GIK decreased the rate of glycogenolysis during ischemia without affecting the rate of glycolysis. We propose that glucose contributed as a glycolytic substrate to a greater extent during ischemia in GIK-treated hearts than in hearts perfused with 3 mM glucose and insulin. The glycogen-sparing effect of GIK demonstrated in these studies could delay the onset of ischemic damage in a clinical setting by prolonging the availability of glycolytic substrate necessary for production of high-energy phosphate.
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PMID:Rates of glycolysis and glycogenolysis during ischemia in glucose-insulin-potassium-treated perfused hearts: A 13C, 31P nuclear magnetic resonance study. 328 83


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