Search PubMed⌕ Search

Biomedical subjects

B Chance

Publications and source records attributed to B Chance.

At least 307 records · Page 17Linked to original sources
PubMed1986

Abnormal skeletal muscle bioenergetics during exercise in patients with heart failure: role of reduced muscle blood flow.

Using phosphorous nuclear magnetic resonance, we have previously demonstrated that patients with heart failure often exhibit abnormal forearm muscle metabolism during forearm exercise. To determine if this altered metabolism is due to reduced muscle flow, we measured forearm blood flow with plethysmography and forearm muscle inorganic phosphate (Pi), phosphocreatine (PCr), and pH with 31P nuclear magnetic resonance spectroscopy at rest and during mild forearm exercise (0.2, 0.4, and 0.6 W) in 21 men with heart failure and in 12 age-matched normal male subjects. The Pi/PCr ratio was correlated with power output and the slope of this relationship was used as an index of forearm metabolism. At rest, both groups had similar Pi/PCr ratios (normal subjects 0.11 +/- 0.05; patients with heart failure 0.11 +/- 0.03; p = NS) and forearm blood flows (normal subjects 2.9 +/- 1.4 ml/min/100 ml; patients with heart failure 2.6 +/- 1.2 ml/min/100 ml; p = NS). In both groups, exercise resulted in a progressive increase in both Pi/PCr and forearm blood flow as power output increased. However, the patients exhibited a steeper slope of the Pi/PCr-to-power output relationship than did the normal subjects (normal subjects 1.4 +/- 0.6 Pi/PCr U/W; patients with heart failure 3.0 +/- 2.4 Pi/PCr U/W; p less than .03). In contrast, forearm blood flow was similar in both groups during exercise (at 0.2 W, 6.3 +/- 3.3 and 6.8 +/- 3.2 ml/min/100 ml in normal subjects and patients with heart failure, respectively; at 0.4 W, 8.7 +/- 6.5 and 8.3 +/- 3.3; at 0.6 W, 12.8 +/- 7.9 and 12.0 +/- 4.6; all p = NS). Nine of the 21 patients with heart failure had slopes of the Pi/PCr-to-power output relationship above the normal range. These nine patients also had forearm blood flows comparable to flows observed in the normal subjects. These data indicate that forearm muscle metabolism during forearm exercise is altered in a subpopulation of patients with heart failure. This metabolic alteration does not appear to be due to decreased muscle blood flow, suggesting that other mechanisms, such as alterations in mitochondrial population or substrate utilization, may be responsible.

Adult↗
PubMed1986

Magnetic resonance spectroscopy of neoplasms.

MRS made especially versatile with current technology of multinuclear coils and time interlacing of signals is appropriately suited to multifaceted tumor biochemistry, where growth is a key metabolic feature. The established results that bioenergetics and lipid metabolite concentrations show a variety of responses in tumor growth and remission in response to anticancer procedures add a further novel dimension to tumor studies by MRS. Finally, the versatility of the multinuclear MRS approach seems most appropriate to the varied nature of cancer.

Animals↗
PubMed1986

Magnetic resonance spectroscopy of the musculoskeletal system.

Magnetic resonance spectroscopy can be used to characterize the bioenergetic state of the musculoskeletal system, and several marker compounds related to the tissue's biochemistry have been found to exist. Potential new techniques involving better spatial localization, spectral editing, and examination of nuclei other than phosphorus are in the developmental stage. Their development over the next few years will determine the extent to which MRS will become a universally used medical tool. However, the results with 31P alone guarantee a continued role in the study of muscular disease, peripheral vascular disease, and hypoxia and ischemia of the neonatal brain.

Adolescent↗
PubMed1986

A comparative study of the tolerance of skeletal muscle to ischemia. Tourniquet application compared with acute compartment syndrome.

In this study, the tolerance of skeletal muscle to tourniquet application (ischemia) and to acute compartment syndrome (ischemia and pressure) was compared. In five animals, the cuff of a pneumatic tourniquet was inflated to 350 millimeters of mercury at the level of the thigh for three hours. In five other animals, an acute experimental compartment syndrome was created in one anterolateral compartment by autologous plasma infusion. The compartment pressure (measured by wick catheter) was maintained at a level equal to the mean arterial pressure for three hours. At three hours, reperfusion was established in both groups, either by tourniquet release or by decompressive fasciotomy and epimysiotomy. During both the ischemic period and a two-hour recovery period immediately thereafter, the mean intracellular pH and high-energy phosphate profile (levels of adenosine triphosphate and phosphocreatine) of the muscles of the anterolateral compartment were monitored non-invasively by phosphorus nuclear magnetic-resonance spectroscopy. Muscle biopsies were done the following day to take specimens for electron microscopic analysis of ultrastructural cellular degeneration. During ischemia, the cellular levels of phosphocreatine decreased at an identical rate in both groups. In contrast, the levels of adenosine triphosphate diminished rapidly in the animals with the compartment syndrome, but remained unchanged in the tourniquet group. Ischemic muscle acidosis was more severe in dogs with the compartment syndrome. In the tourniquet group, the phosphocreatine, adenosine triphosphate, and pH were all normal within fifteen minutes after release of the tourniquet, but these values remained depressed even two hours after fasciotomy in the group with compartment syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

Metabolic control principles and 31P NMR.

31P NMR is a unique research tool for studying metabolism during exercise. This communication gives the underlying theory and experimental data for obtaining the transfer characteristic relating work and NMR-determined metabolic paramenters, particularly the ratio of free inorganic phosphate to phosphocreatine (Pi/PCr). Furthermore, illustrations of the types of transfer characteristics observed in different individuals and different training regimens can be obtained, including both hyperbolic (Michaelis-Menten) and sigmoid transfer characteristics. With a hyperbolic transfer characteristic, oxygen delivery appears to be adequate to support the exercise regimen over the range studied (up to 50% of Vmax), whereas with a sigmoid transfer characteristic, there appears an imprint of limited oxygen delivery on the kinetics from rest up to 50% of Vmax. These two types of transfer functions are appropriate to explain the transition to anaerobic metabolism (anaerobic threshold), with a hyperbolic transfer characteristic representing a graded transition; and a sigmoid transfer characteristic representing an abrupt transition. A sigmoid transfer characteristic may involve greater lactate accumulation at submaximal exercise levels, and in both types of transfer characteristic sufficient aerobic lactate is formed to meet the metabolic demand for pyruvate. The results suggest an important role for 31 P NMR in studies of energy-related metabolites as a means of determining exercise performance in terms of regulation of tissue oxidative metabolism and oxygen delivery to tissue.

Adenosine Diphosphate↗
PubMed1986

Energy metabolism in relation to oxygen supply in contracting rat skeletal muscle.

The regulation of the energy metabolism in contracting skeletal muscle is under close control, and several regulating factors have been reported. The aim of this study was to investigate the importance of the oxygen supply as a limiting factor for muscle performance during contractions and recovery from contractions. To perform well-controlled standardized experiments on contracting skeletal muscle, the perfused rat hind limb model was developed. The 31P NMR technique was adapted to the rat hind limb model. This enabled continuous nondestructive monitoring of the energy state at various levels of muscular activity. Significant correlations were found between oxygen delivery and oxygen consumption, lactate release, and glucose uptake, respectively. An increased degree of fatigue was observed at lower oxygen deliveries. In both soleus and gastrocnemius muscles, oxygen delivery correlated with the intramuscular concentrations of phosphocreatine (PCr), lactate, and glycogen. The 31P NMR experiments showed a correlation between oxygen delivery and the steady-state level of PCr/inorganic phosphate (Pi) during the contraction period. The rate of recovery in PCr/Pi after the contraction was also dependent on oxygen delivery. The results demonstrate a causal relationship between oxygen supply and energy state in contracting as well as recovering skeletal muscles.

Adenosine Triphosphate↗
PubMed1985

The oxygen reaction of the cytochrome d-terminated respiratory chain of Escherichia coli at sub-zero temperatures. Kinetic resolution by EPR spectroscopy of two high-spin cytochromes.

The oxygen reaction of the fully reduced respiratory chain in membranes from oxygen-limited Escherichia coli was studied at sub-zero temperatures using EPR spectroscopy. Laser photolysis of CO-liganded cytochrome oxidase d precedes oxidation of at least 2 kinetically separable high-spin cytochromes. At -120 to -100 degrees C, a rhombic signal appears, attributable to cytochrome d, followed at above -100 degrees C, by appearance of a second, axial signal near g = 6, here assigned to cytochrome(s) b, and changes in the redox state of iron-sulphur clusters. The data kinetically resolve the 2 high-spin signals attributed to the oxidase complex and suggest schemes for electron flow to oxygen.

Cell Membrane↗
PubMed1985

High spatial resolution readout of 3-D metabolic organ structure: an automated, low-temperature redox ratio-scanning instrument.

Intraorgan compartmentation of metabolic processes plays an important role in the understanding of the physiological function of the integrated organ under normal as well as under pathological conditions. We describe here a technique by which 3-D information on tissue redox state may be obtained by means of automated scanning of surface fluorescence. The instrument allows for serial scanning of frozen tissue. A typical scan of a tissue volume of 3 X 3 X 2 mm at a linear resolution of 50 micron and a spatial resolution of ca. 3 X 10(-7) ml includes 144,000 single-point measurements of pyridine nucleotide and flavoprotein fluorescence within the tissue block. The scanning process is fully computerized and programs have been developed which allow 2- or 3-D reconstruction of the data in terms of "redox ratio models," exemplified here by a 3-D model of a spreading depression wave in the cerebral cortex of a gerbil.

Animals↗
PubMed1985

Bioenergetic studies of mitochondrial oxidative phosphorylation using 31phosphorus NMR.

The relationship between phosphorylation ratio [( ATP])/[ADP][Pi], phosphocreatine (PCr)/Pi, and ATPase activity was determined for isolated rat heart mitochondria, and the use of phosphorylation ratio and/or PCr/Pi as bioenergetic indices (Chance, B., Eleff, S., Leigh, J. S., Sokolow, D., and Sapega, A. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 6714-6718) was evaluated. Isolated rat heart mitochondria were suspended at low concentration (0.5-2.0 mg of protein/ ml) in oxygenated KCl/sucrose/4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid medium at 25 degrees C and pyruvate, malate, PCr, ATP, Pi, and Mg2+ were added. Changes in extramitochondrial phosphorus compounds were followed by 31P NMR. The ATPase activity was varied by the addition of potato apyrase. It was found that the logarithm of steady state PCr/Pi decreased linearly with increasing ATPase rate with a PCr/Pi intercept of 32.8 at 0 ATPase rate. The log phosphorylation ratio was also linearly related to the ATPase rate with an extrapolated maximum value of 6.87 at 0 ATPase rate, corresponding to a phosphorylation ratio of 7.41 X 10(6) M(-1) and a delta GATP of -16.3 kcal. The phosphorylation ratio in these experiments (for state 4 respiration) was greater by 1 or 2 orders of magnitude than previously reported for either isolated mitochondria or for whole tissue.

Adenosine Diphosphate↗
PubMed1985

Resonance Raman spectroscopy and enhanced photoreducibility for the 420 nm pulsed form of cytochrome oxidase.

Resonance Raman (RR) spectra, with 413.1 nm Kr+ laser excitation, are reported for cytochrome oxidase in resting, reduced, and 428 nm (oxygenated) forms, and for the first time, in the 420 nm (pulsed) forms [(1984) J. Biol. Chem. 259, 2073-2076]. The differences between the resting, 420 nm, and 428 nm forms' RR spectra are small. All these forms contain FeIII only, as indicated by single v4 bands at approximately 1371 cm-1, and the reoxidized forms show partial conversion from high- to intermediate- or low-spin heme a3 (intensity shift from 1575 to 1588 cm-1 for v2). The 420 nm form differs strikingly from both the 428 nm and resting forms, however, in being much more readily photoreduced by the laser illumination. This property is linked to the protein conformational change believed to be responsible for the greater accessibility to exogenous ligands of the heme a3 in the 420 nm form.

Animals↗
PubMed1985

In vivo nuclear magnetic resonance imaging of lithium.

Magnetic resonance imaging techniques have previously been applied to 1H, 23Na, 31P, and 19F nuclei. This is the first report of application of these techniques to 7Li. Lithium images of both aqueous phantoms and a rat abdomen are presented. Applications of this technique to humans are discussed.

Animals↗
PubMed1985

Nuclear magnetic resonance: an overview of its spectroscopic and imaging applications in pediatric patients.

Magnetic resonance (MR) is a technique that permits the noninvasive evaluation of morphologic features and function based on the distribution of protons and other selected elements. We present a basic description of MR and illustrate both 31P-MR spectroscopy and proton imaging applications in pediatric patients. The applications of these techniques are diverse, and are presented concisely in an attempt to give pediatricians an overview of this new technology and its potential role in patient management.

Adolescent↗
PubMed1985

Diagnosis and therapeutic evaluation of a pediatric case of cardiomyopathy using phosphorus-31 nuclear magnetic resonance spectroscopy.

An 8 month old girl presented with undiagnosed non-anatomic congenital cardiomyopathy with massive cardiomegaly on chest X-ray film. Her older sibling had died suddenly at 6 months of age from what appeared to be a similar abnormality. Utilizing phosphorus-31 nuclear magnetic resonance (P-31 NMR) surface coil spectroscopy, a metabolic disorder was demonstrated in both her myocardium and skeletal muscle, revealing a phosphocreatine (PCr) to inorganic phosphate (Pi) ratio of half of that for a normal control infant. Manipulation of serum substrate availability indicated that medium chain triglycerides alone did not improve myocardial metabolism, but that intravenous glucose or oral carbohydrate loading raised the myocardial PCr/Pi ratio from 1.0 +/- 0.05 to 1.8 +/- 0.1 (p less than 0.01) without significantly affecting the PCr/Pi value of her resting skeletal muscle. This study demonstrates the feasibility of using P-31 nuclear magnetic resonance to evaluate the biochemistry of the human myocardium in vivo and to diagnose a metabolic abnormality. Phosphorus-31 nuclear magnetic resonance can thus be used to optimize therapy for human disease.

Cardiomegaly↗
PubMed1985

Control of oxidative metabolism and oxygen delivery in human skeletal muscle: a steady-state analysis of the work/energy cost transfer function.

The concept of transfer function for organ performance (work output vs. biochemical input) is developed for skeletal and cardiac muscle under steady-state exercise conditions. For metabolic control by the ADP concentration, the transfer function approximates a Michaelis-Menten hyperbola. Variation of the work identifies metabolic operating points on the transfer function corresponding to ADP concentrations or to a ratio of inorganic phosphate to phosphocreatine that can be determined by phosphorus nuclear magnetic resonance. This operating point is characterized by the fraction (V/Vmax) of maximal activity of oxidative metabolism in the steady state. This quantity appears to be useful in predicting the degree to which metabolic homeostasis is effective; poorly controlled metabolic states can readily be identified and are used in the diagnosis and therapy of metabolic disease in the organs of neonates and adults.

Adenosine Diphosphate↗