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W P Aue

Publications and source records attributed to W P Aue.

18 recordsLinked to original sources

Measurement of lactate in acutely ischemic rat kidneys using magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: Quantification of lactate in the kidney by 1H magnetic resonance spectroscopy (MRS) is a difficult task because of the presence of large amounts of peri-renal fat. When an editing scheme is used to detect lactate that filters out all resonances except lactate, there is no suitable metabolite to serve as an internal standard. In this study, the authors evaluate the potential of MRS to measure the absolute lactate concentration in rat kidneys during acute ischemia using MRS. MATERIALS AND METHODS: The authors propose a method based on a double resonance lactate editing scheme used in combination with the fully relaxed water peak as an internal standard. Experiments were performed on the left kidney rendered ischemic in eight rats. RESULTS: Renal lactate concentrations measured by MRS were compared with values derived from chemical analysis. The mean (+/- standard deviation) renal lactate concentrations measured by MRS and determined chemically were 12 +/- 1.2 umol/g, and 12.94 +/- 1.07 umol/g wet weight, respectively. The coefficient of variation for paired observations was 2.96%, indicating excellent agreement between the two methods used for measuring lactate. DISCUSSION: The study results demonstrate that it is possible to assess the lactate concentration in a rat model of ischemic kidney with MRS and suggest that the total lactate pool is detectable by this method under these experimental conditions.

Animals↗

[Energy metabolism of the brain, detected with 31-P magnetic resonance spectroscopy during extracorporeal circulation in the rabbit].

The question of a possible brain damage during open heart surgery using extracorporeal circulation is still a problem, especially in infants with circulatory arrest under deep hypothermia. During the last years Magnetic Resonance Spectroscopy was developed, and with this method we have now a possibility to study brain energy metabolism non-invasively and continuously. Our aim was to develop an animal model (rabbit) for studying brain energy metabolism by 31-P Magnetic Resonance Spectroscopy during extracorporeal circulation. In a first step we have shown that the influence of hypothermia on energy metabolism in the brain can be measured in the intact animal by MR-Spectroscopy. In a second step a non-magnetic heart-lung machine for rabbits was constructed and is described here. We get a completely normal brain spectrum in the beginning and after two hours of extracorporeal circulation. The spectrum is also normal on extracorporeal circulation at 35 degrees C and during cooling down to 18 degrees C. With this animal model it will be possible to study different variables of extracorporeal circulation such as duration of circulatory arrest under deep hypothermia or changes of the priming including pharmacological changes.

Adenosine Triphosphate↗

In vivo 31P NMR spectroscopy of energy rich phosphates in the brain of the hyperammonemic rat.

Hyperammonemia is a major contributing factor to the neurological abnormalities observed in hepatic encephalopathy and in congenital defects of ammonia detoxication. In rats variable changes in labile energy rich phosphates in the brain have been observed in hyperammonemia using biochemical methods. Using 31P-NMR spectroscopy however no significant changes of the relative concentrations of the energy rich phosphates alpha, beta and gamma-ATP, phosphocreatine, inorganic phosphate and the pH were found in the fronto parietal cortex of the urease treated hyperammonemic rat. Alterations in the metabolites of these compounds do not appear to be a major pathomechanism of ammonia toxicity in this brain area.

Ammonia↗

Study of acute renal ischemia in the rat using magnetic resonance imaging and spectroscopy.

Magnetic resonance (MR) imaging and spectroscopy, chemical lactate measurements, and microscopic examinations were performed to investigate acute renal ischemia in rats. MR images (1H) and spectra (31P and 1H) were acquired on a 2.0-T superconducting small-bore magnet by using implanted coils. Occlusion of the renal artery induced a significant decrease in signal intensity of the renal parenchyma on T2-weighted images, which was most obvious in the outer medulla (-50 +/- 15%, n = 8, P less than 0.001) and was the result of venous congestion, as verified histologically, 31P spectroscopy demonstrated a drop in pH from 7.3 +/- 0.2 to 6.6 +/- 0.2 (n = 18, P less than 0.001), characterized by a time constant (Tc) in the same range as that of the depletion of ATP (2.3 +/- 1.3 min versus 1.9 +/- 1.2 min, n = 10, P = ns). By means of 1H spectroscopy, a lactate peak was detected within 1.5 to 4 min of ischemia, still increasing in intensity after 1 h of ischemia. The Tc of the lactate buildup (15.9 +/- 7.5 min, n = 8) was significantly longer than that of the drop in pH (P less than 0.005). The chemically measured intrarenal concentration of lactate was 1.3 +/- 0.5 mumol/g in control kidneys and 8.7 +/- 3.2 mumol/g (P less than 0.005) in kidneys made ischemic for 1 h. The present study demonstrated important features of acute renal ischemia: (a) acute ischemia induces venous congestion in the medulla; (b) accumulation of lactate is not the main cause of the intracellular acidification observed during ischemia.

Animals↗

Lactate distribution in ischemic rat kidney by 4D spectroscopic imaging.

A lactate map of the rat kidney is presented, using a four-dimensional spectroscopic imaging technique in connection with a double resonance editing scheme. A voxel size of 12 microL has been obtained, and we show that eddy currents do not affect the line shape of an individual voxel.

Animals↗

1H spectroscopic imaging at high spatial resolution.

Spectroscopic imaging and single voxel localization are compared with respect to the signal to noise ratio per unit time and unit volume. It is shown experimentally that, when using the same experiment time and the same voxel size, both methods give similar results. In order to investigate the localization limits of spectroscopic imaging, lipid distribution in a single large cell was measured and correlated with gradient echo microscopy.

Animals↗

Correlation between 31P NMR phosphomonoester and biochemically determined phosphorylethanolamine and phosphatidylethanolamine during development of the rat brain.

Phosphomonoesters were measured in the developing rat brain by in vivo and in vitro 31P nuclear magnetic resonance (NMR) spectroscopy and by classical biochemical methods. In vitro NMR showed that the main component of the phosphomonoester peak is phosphorylethanolamine. Phosphomonoesters measured by in vivo NMR decreased during development at the same rate as the biochemically estimated phosphorylethanolamine. Phosphorylethanolamine, a precursor of the membrane lipid phosphatidylethanolamine, decreased during development parallel to an increase of the lipid phosphatidylethanolamine, which was measured biochemically. These studies show that 31P NMR can be used to monitor brain development in vivo.

Aging↗

[Clinical applications of magnetic resonance spectroscopy].

In this overview the physics of magnetic resonance spectroscopy (MRS) are briefly discussed. The biochemical pathways which can be investigated by MRS in physiological and pathological states are presented. The potential clinical applications of this method to the musculoskeletal system, heart, brain, liver and kidney are examined.

Brain↗

Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31P-NMR and implications for adriamycin-induced cardiotoxicity.

In vivo 31P-NMR was used to measure the effects of the anti-tumor drug adriamycin on the energy metabolism of rat heart. The exclusive acquisition of NMR signal from cardiac muscle was assured by positioning a solenoidal radio-frequency NMR coil around the heart. Appropriate control experiments verified that 31P-NMR spectra solely originated from this organ. Acute effects occurring shortly after adriamycin administration are expressed in 31P spectra as a dose-dependent decline in the cardiac levels of phosphocreatine, after which stabilization at a new steady-state level occurs. These acute effects of a single dose are complete in 30-60 min and no significant further changes take place within 150 min after drug introduction. Longer-term effects of single high doses and of multiple lower doses were measured up to a week after the initiation of treatment. It seemed that at a total dose of 20 mg/kg, drug-induced interference with cardiac energy metabolism was more pronounced than at the same dose in the acute phase. These 31P-NMR data demonstrate that adriamycin treatment is accompanied by a decrease of the cardiac phosphocreatine/ATP ratio which might be an expression of the well-established cardiotoxicity of the drug.

Adenosine Triphosphate↗

Cerebral metabolic studies in situ by 31P-nuclear magnetic resonance after hypothermic circulatory arrest.

Cerebral high energy phosphates were studied in the intact rabbit brain using nuclear magnetic resonance spectroscopy. The effect of hypothermia on degradation kinetics in total ischemia due to circulatory arrest was examined, measuring phosphocreatine, adenosine triphosphate, and inorganic phosphate as a function of time at three different temperatures (35, 24, 21 degrees C). Phosphocreatine- and ATP-decays followed single exponential functions at all three temperatures. The half-life times increased by approximately a factor of three upon lowering the temperature from 35 to 21 degrees C with activation energies of 15-20 kcal/mol, which corresponds to values of Q10 between 2.4 and 3.2. In the temperature range studied, no critical temperature was found below which metabolism would stop completely. We conclude that nuclear magnetic resonance spectroscopy allows, in the intact animal, quantitative assessment of the influence of hypothermia on energy metabolism in the brain. This influence is a major concern in the field of cardiac surgery in infants and children who are often operated in total circulatory arrest under deep hypothermia.

Adenosine Triphosphate↗

Phosphocreatine content and intracellular pH of calf muscle measured by phosphorus NMR spectroscopy in occlusive arterial disease of the legs.

Energy metabolism of calf muscle was assessed non-invasively by phosphorus (31P) NMR spectroscopy in eleven patients with symptomatic arterial occlusion and in seven matched controls. Phosphocreatine (PCr) content and pH values decreased during non-ischaemic foot exercise to lower values in severely afflicted patients but in all patients, as a group, they were not significantly decreased compared to controls. In contrast, recovery from ischaemic exercise (arterial occlusion by a tourniquet) demonstrated significant differences between patients and controls. Intracellular pH and PCr recovered more slowly in patients than in controls; PCr recovery proceeded exponentially with a recovery half-time of 203 +/- 74 s in patients compared to 36.7 +/- 5.5 s in controls (P less than 0.02). Phosphocreatine (PCr) recovery after ischaemic exercise correlated significantly with the degree of arterial stenoses as assessed by Doppler ultrasound (r = 0.739, P = 0.019) and by angiography (r = 0.885, P = 0.005), suggesting that the degree of large vessel stenoses limits the postischaemic increase in mitochondrial oxidative phosphorylation. Reactive blood flow after ischaemia failed to correlate with PCr recovery or with the degree of arterial stenoses. Phosphorus (31P) NMR spectroscopy provides, therefore, quantitative parameters of muscle energy metabolism in patients with peripheral arterial occlusions.

Arterial Occlusive Diseases↗

Extremity bone tumors: evaluation by P-31 MR spectroscopy.

High-resolution P-31 MR spectra were obtained in four patients with bone tumors of their distal extremities. In one case the tumor, a Ewing sarcoma of the tibia, was investigated during clinical remission after radiation therapy and chemotherapy. The other three cases - one low-grade chondrosarcoma of the tibial head, one malignant fibrous histiocytoma of the tibia, and one chondroblastoma of the medial femoral condyle - showed clinically active tumor growth, with corresponding increased metabolism as demonstrated by bone scintigraphy. The spectra of the three active tumors indicated a comparably high adenosine triphosphate content, similar to previously published spectra from animal tumors or human tumors implanted into animals. There were also high resonances of inorganic phosphate and low resonances of phosphocreatine; there were definite peaks in the phosphodiester and phosphomonoester regions, indicating the existence of these metabolites in the tumors. Slight but definite changes in the metabolite content were observed in one tumor after chemotherapy. The spectra of the unaffected leg did not show any well-resolved P-31 signals, which is typical for healthy bone. These are the first P-31 MR spectra of human bone tumors measured in patients to our knowledge.

Adolescent↗

Ketogenesis in the living rat followed by 13C NMR spectroscopy.

The metabolic fate of 13C1-labeled butyrate in the liver of living rats has been studied by 13C NMR. The formation of the ketone bodies acetoacetate and beta-hydroxybutyrate was observed in vivo as well as resonances from glutamate, glutamine, and carbonate. The observed time course of these metabolites demonstrates the potential of the technique to measure enzyme kinetics in vivo and also to measure the enzyme capacity of a given organ to metabolize a substrate. The in vivo spectra were compared to in vitro spectra of the excised liver and perchloric acid extracts of the liver. Observation of the metabolites and monitoring of their time course in vivo would not have been possible without distinct improvements in the spectral resolution and the spatial localization of the radio-frequency field within the liver. As a novel approach, we have selected the carbonyl region of the 13C NMR spectra for identifying the ketone bodies and other oxidation products in the liver.

3-Hydroxybutyric Acid↗

Solid-state phosphorus-31 nuclear magnetic resonance studies of synthetic solid phases of calcium phosphate: potential models of bone mineral.

Phosphorus-31 NMR spectra have been obtained from a variety of synthetic, solid calcium phosphate mineral phases by magic angle sample spinning. The samples include crystalline hydroxyapatite, two type B carbonatoapatites containing 3.2 and 14.5% CO3(2-), respectively, a hydroxyapatite in which approximately 12% of the phosphate groups are present as HPO4(2-), an amorphous calcium phosphate, monetite, brushite, and octacalcium phosphate. Spectra were observed by the standard Bloch decay and cross-polarization techniques, as well as by a dipolar suppression sequence, in order to distinguish between protonated and unprotonated phosphate moieties. The spectra of the synthetic calcium phosphates provide basic information that is essential for interpreting similar spectra obtained from bone and other calcified tissues.

Bone and Bones↗

Investigation of the mineral phases of bone by solid-state phosphorus-31 magic angle sample spinning nuclear magnetic resonance.

Phosphorus-31 magic angle sample spinning NMR spectra have been employed to investigate the structure and composition of the mineral deposits in chicken bone. Three different pulse sequences, Bloch decay, cross-polarization, and dipolar suppression, were employed to obtain spectra from bone specimens of varying age. These were compared to the spectra obtained from a variety of crystalline and noncrystalline synthetic calcium phosphate solids used as reference standards. The results suggest that the most suitable model for the major solid calcium phosphate mineral phase in bone is a hydroxyapatite containing approximately 5-10% CO32- and approximately 5-10% HPO42- groups, the latter in a brushite-like configuration. From the NMR line shapes it was deduced that the fraction of HPO42- groups was highest in the youngest bone and decreased progressively with increasing age of the specimen.

Animals↗

[Topical nuclear magnetic resonance--a non-invasive probe for biochemical measurements in living organisms].

Topical Nuclear Magnetic Resonance (TNMR) is a noninvasive and non-hazardous new technique which allows local observation of chemical composition and metabolism in living objects. This article gives an introduction into TNMR, along with a brief discussion on instrumentation. Some clinically relevant TNMR results from literature will also be described and illustrated with our own experimental spectra of a forearm.

Adenosine Triphosphate↗

Magnetic resonance spectroscopy for assessing myocardial rejection in the transplanted rat heart.

Traditionally, detection of heart rejection after heart transplantation is based on histologic grading of endomyocardial biopsy specimens. The value of magnetic resonance spectroscopy for determining heart rejection was assessed in rejecting and nonrejecting isografts and allografts using energy-rich phosphate spectroscopy. In 46 rats a heterotopic abdominal heart transplantation was performed, and animals were divided into the following groups: six isografts (no rejection), five untreated allografts (severe rejection), and 35 immunosuppressed allografts (mild to moderate rejection). One week after transplantation magnetic resonance spectroscopy was performed, and data were correlated to histologic findings (rejection grades according to Stanford and the New International Working Formulation classifications and relative volume of viable myocardium). Magnetic resonance spectroscopy allows detection of moderate to severe rejection with significant alterations in the energy-rich phosphates such as a decrease in the ratio of phosphocreatine/inorganic phosphate, phosphomonoester/inorganic phosphate, and beta-adenosine triphosphate/inorganic phosphate. A significant correlation was found between spectroscopic changes (phosphocreatine/inorganic phosphate) and histologic rejection (correlation coefficient r = 0.47, p < 0.005) and/or the amount of relative volume of viable myocardium and phosphocreatine/inorganic phosphate (r = 0.58) or beta-adenosine triphosphate/inorganic phosphate (r = 0.63), respectively. In conclusion magnetic resonance spectroscopy permits detection of moderate to severe degrees of heart rejection with a sensitivity of 85% and a specificity of 61%. Changes in the energy-rich phosphates correlate with the histologic grading of heart rejection and the relative volume of viable myocardium. Magnetic resonance spectroscopy appeared to be a valid technique for detecting myocardial rejection after heart transplantation in the reported experimental model.

Adenosine Triphosphate↗