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Biomedical subjects

B Chance

Publications and source records attributed to B Chance.

At least 235 records · Page 13Linked to original sources
PubMed1988

Acute volume loading studied in cat myocardium with 31P nuclear magnetic resonance.

To study the effects of acute volume loading on myocardial metabolic and mechanical function, seven cats were volume loaded via anastomosis of the abdominal aorta to the vena cava (AV shunt). Metabolic effects were evaluated with 31P nuclear magnetic resonance (NMR). Mechanical function was evaluated with heart rate X systolic blood pressure product (HR X SBP). Shunts were opened for 1-2 h during which time phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi), and HR X SBP were monitored. High-energy phosphate energetics as determined by Pi/PCr and PCr/ATP ratios were correlated with HR X SBP. Opening of the AV shunts was associated with an increase (four cats) or a decrease (three cats) in HR X SBP. Pi/PCr ratios increased and PCr/ATP ratios decreased in cats with an increase in HR X SBP. In cats with a decrease in HR X SBP, Pi/PCr and PCr/ATP generally did not change significantly. In summary, acute volume loading could be associated with an increase or decrease in myocardial external work as evaluated by HR X SBP, accompanied by metabolic changes suggestive of appropriate induction of state 3 metabolism (active metabolic state: ADP + Pi----ATP) in those cats with increased mechanical work, and minimal change in bioenergetics in cats with no or minimal increase in mechanical work. These induced metabolic responses to myocardial mechanical loading can be evaluated with 31P NMR techniques and may provide insight into in vivo metabolic control mechanisms.

Adenosine Triphosphate↗
PubMed1988

Concurrent measurements of cerebral blood flow, sodium, lactate, and high-energy phosphate metabolism using 19F, 23Na, 1H, and 31P nuclear magnetic resonance spectroscopy.

A new NMR technique for nondestructive, noninvasive, nonradioactive concurrent measurements of blood flow and several energy-dependent metabolites were applied to in situ cat brain during high cerebral blood flow states (seizures) and low flow states (carotid occlusion plus hemorrhagic shock). An inductively coupled, quadruple-tuned surface coil with a 50-ohm match at all relevant frequencies was used for both excitation and receiving. A broadband spectometer was used to measure the 31P spectrum (PCr, ATP, Pi, and pH), a water-suppressed 1H spectrum (lactate), 23Na, and 19F (blood flow via CHF3 washout). Each nucleus was excited at an independently determined rate. Sodium, with a short T1, was excited more frequently than phosphorus. The results qualitatively agreed with other techniques. Blood flow greatly increased during seizures with a 10% decrease in the Na signal, minimal lactate accumulation, no pH shift, and a change in the PCr-to-Pi ratio from 3.4 to 1.7. During carotid occlusion plus hypotension blood flow, PCr and ATP decreased to less than 10% of baseline values. Changes in PCr and Pi preceded parallel changes in Na and ATP. These experiments demonstrated the feasibility of concurrent measurements of physiologically induced changes in high-energy phosphates, lactate, sodium, and blood flow from the same volume of brain, in a nondestructive manner using NMR spectroscopy.

Adenosine Triphosphate↗
PubMed1988

Detection of muscle injury in humans with 31-P magnetic resonance spectroscopy.

Strenuous exercise can result in muscle injury that may persist for 2 weeks. Our purpose was to determine if muscle injury can be detected with 31-P magnetic resonance spectroscopy. Normal subjects performed repeated lengthening contractions with either arms or legs designed to result in mild muscle injury. One hour after the arm exercise, there was a significant increase in the inorganic phosphate to phosphocreatine ratio (Pi/PCr), with the maximum increase in Pi/PCr occurring 1 day postexercise (0.12 +/- 0.01 to 0.21 +/- 0.05). Pi/PCr remained elevated for 3-10 days. Similar results were seen following the leg exercise protocol. ATP/(Pi + PCr) decreased in all the arm exercised subjects. Exercise protocols that did not contain lengthening contractions did not result in changes of Pi/PCr or ATP/(Pi + PCr). Patients with various neuromuscular diseases with evidence of muscle damage (elevated CK, muscle soreness, and histopathological findings) also showed increased Pi/PCr at rest. We conclude that elevated Pi/PCr at rest can reflect nonspecific muscle damage in normal and diseased subjects.

Adult↗
PubMed1988

Metabolic myopathy in canine muscle-type phosphofructokinase deficiency.

In vivo 31phosphorus nuclear magnetic resonance spectroscopy (P-NMR) of the anterior tibialis muscle was used to investigate the metabolic myopathy of inherited muscle-type phosphofructokinase (PFK) deficiency in four (homozygous) dogs who had mild exercise intolerance, rare muscle cramps, increased serum creatine kinase activity, but no myoglobinuria. During isometric muscle work induced by indirect electrical stimulation, and subsequent recovery, changes in the ratio of phosphocreatine (PCr) and inorganic phosphates (Pi) were comparable in muscle of PFK-deficient and normal dogs and indicated a large capacity for arobic oxidative phosphorylation in canine muscle. The progressive accumulation of sugar phosphates (PME) during graded exercise clearly demonstrated the glycolytic block in PFK-deficient dogs. During a muscle contracture, induced by acute muscle stimulation, PFK-deficient muscle became completely depleted of PCr and ATP, accumulated large amounts of PME, and recovered very slowly. We conclude that PFK-deficient dogs have a metabolic myopathy that demonstrated some but not all the features recognized in the human disorder.

Animals↗
PubMed1988

The simultaneous measurements of tissue oxygen concentration and energy state by near-infrared and nuclear magnetic resonance spectroscopy.

The oxygenation and energy states of brain tissues were measured simultaneously by near-infrared photometry and nuclear magnetic resonance spectroscopy in situ. In both cat and dog, the critical hemoglobin oxygenation was 10%, below which the ratio of phosphocreatine (PCr) to inorganic phosphate (Pi) started to fall. The fall of PCr/Pi paralleled the reduction of copper in cytochrome aa3. The separation of the cytochrome aa3 signal from that of hemoglobin by our optical method was confirmed by the substitution of blood by fluorocarbon solution. The energy-oxygen diagram (PCr/Pi against hemoglobin oxygenation, HbO2) was the same in normal- and fluorocarbon substituted cats, but energy curve shifted to the right in the latter when PCr/Pi plotted against the inspired oxygen, FiO2.

Animals↗
PubMed1988

Fiber optic surface fluorometry/reflectometry and 31-p-NMR for monitoring the intracellular energy state in vivo.

Various members of the respiratory chain exhibit different optical properties in the reduced and oxidized forms, thus enabling the non-invasive monitoring of various organs in vitro as well as in vivo. Since the pioneering work of Chance, Cohen, Jobsis and Schoener in 1962, many groups of investigators adopted their approach in monitoring NADH oxidation reduction states in vivo for the brain as well as for other body organs. In 1972, we introduced flexible, optical fibers into the surface fluorometry replacing the usual "rigid" optical system used by other groups. During the last decade, this technique has been developed, improved and applied to many experimental setups in brain research and very recently was combined with 31P NMR spectroscopy for the puppy and the adult dog brain in vivo. In our system, the effects of movement artifacts and changes in blood oxygenation are negligible while the effects of tissue absorption or blood volume changes are considerable and could be minimized by subtraction of the reflectance signal from that of the fluorescence (1:1 ratio) providing the corrected fluorescence signal.

Anaerobiosis↗
PubMed1988

Linkage between energy status of perivascular cells and mineralization of the chick growth cartilage.

The objective of this investigation was to investigate the relationship between the energy status of epiphyseal chondrocytes of the chick growth cartilage and the development of mineralization. A microfluorimetric scanning technique was used to measure the reduced pyridine nucleotide content of transverse sections of freeze-trapped cartilage; these measurements were related to tissue structure by scanning electron microscopy. The results of this study show that the energy status of cells in the hypertrophic region of the growth cartilage is more complex than was previously believed. In hypertrophic cartilage, most chondrocytes are in a reduced state. However, in the early hypertrophic region, the vascular channels that penetrate the cartilage from the metaphysis exert a profound local effect on the energy metabolism of perivascular chondrocytes. Thus, around each of the channels, there exists a zone of chondrocytes about 40-60 micron wide which exhibits a low fluorescence yield. The fluorescence level suggests that these perivascular cells have a higher level of oxidative metabolism than hypertrophic chondrocytes that are a distance (greater than 150 micron) from the vascular channels. This finding, in conjunction with our earlier observation that mineralization is first seen in the perivascular region, leads us to the conclusion that mineralization is associated with cellular oxidative activity. We now reject the long-held concept that in cartilage the development of mineralization is entirely due to tissue hypoxia.

Animals↗
PubMed1988

An in vivo phosphorus nuclear magnetic resonance study of the variations with age in the phosphodiester content of human muscle.

Human gastrocnemius and slow twitch muscles contain phosphodiesters that may be detected in vivo by phosphorus nuclear magnetic resonance (NMR). This work represents a study of 354 spectra obtained from healthy subjects of various ages and from patients with peripheral vascular disease. The analysis of the data indicate a correlation between the concentration of phosphodiesters and age. By comparing the data obtained with healthy subjects and patients it is concluded that the increase in phosphodiesters is not due to disease, but to ageing itself. The significance of this increase is discussed.

Adenosine Triphosphate↗
PubMed1988

Brain oxidative metabolism of the newborn dog: correlation between 31P NMR spectroscopy and pyridine nucleotide redox state.

The effects of both anoxia and short- and long-term hypoxia on brain oxidative metabolism were studied in newborn dogs. Oxidative metabolism was evaluated by two independent measures: in vivo continuous monitoring of mitochondrial NADH redox state and energy stores as calculated from the phosphocreatine (PCr)/Pi levels measured by 31P nuclear magnetic resonance (NMR) spectroscopy. The hemodynamic response to low oxygen supply was further evaluated by measuring the changes in the reflected light intensity at 366 nm (the excitation wavelength for NADH). The animal underwent surgery and was prepared for monitoring of the two signals (NADH and PCr/Pi). It was then placed inside a Phosphoenergetics 260-80 NMR spectrometer magnet with a 31-cm bore. Each animal (1-21 days old) was exposed to short-term anoxia or hypoxia as well as to long-term hypoxia (1-2 h). The results can be summarized as follow: (a) In the normoxic brain, the ratio between PCr and Pi was greater than 1 (1.2-1.4), while under hypoxia or asphyxia a significant decrease that was correlated to the FiO2 levels was recorded. (b) A clear correlation was found between the decrease in PCr/Pi values and the increased NADH redox state developed under decreased O2 supply to the brain. (c) Exposing the animal to moderately long-term hypoxia led to a stabilized low-energy state of the brain with a good recovery after rebreathing normal air. (d) Under long-term and severe hypoxia, the microcirculatory autoregulatory mechanism was damaged and massive vasoconstriction was optically recorded simultaneously with a significant decrease in PCr/Pi values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Comparison of time-resolved and -unresolved measurements of deoxyhemoglobin in brain.

Continuous (CW) and pulsed light were used for the noninvasive measurement of hemoglobin oxygenation in tissues. A dual wavelength method of continuous illumination spectroscopy used 760 nm (deoxyhemoglobin peak) and 800 nm (an oxyhemoglobin-deoxyhemoglobin isosbestic point) to measure the kinetics and extent of oxyhemoglobin deoxygenation in brains during mild ischemia/hypoxia. Absorption and scattering were modeled in an artificial milk/yeast blood system, which gave an exponential relationship between absorption and optical path length to a depth of 7 cm. Time-resolved spectroscopy (10-ps resolution) afforded a display of the times and distances of arrival of photons emitted by the cat brain in response to a 10-ps input pulse. The emitted photons rose to a peak in a fraction of a nanosecond and declined exponentially over a few nanoseconds. The half-time of exponential decay corresponds to photon migration over a distance of 4 cm. Exponential light emission continued for several more nanoseconds when the brain was encased by the skull, which plays a key role in prolonging light emission. The exponential decline of light intensity has a value [exp(-microL)], where L is the path length determined from the time/distance scale and mu is the characteristic of the migration of light in the brain. The factor mu is increased by increasing absorption, and mu' = epsilon C where epsilon and C are the Beer-Lambert parameters of extinction coefficient (epsilon) and concentration (C). Thus, deoxyhemoglobin can be quantified in brain tissues.

Animals↗
PubMed1988

Energy metabolism of the untrained muscle of elite runners as observed by 31P magnetic resonance spectroscopy: evidence suggesting a genetic endowment for endurance exercise.

The purpose of this study was to investigate whether genetically determined properties of muscle metabolism contribute to the exceptional physical endurance of world-class distance runners. ATP, phosphocreatine, inorganic phosphate, and pH were quantitatively determined by 31P nuclear magnetic resonance spectroscopy in the wrist flexor muscles of elite long-distance runners and sedentary control subjects. These muscles had not been exposed to any specific program of exercise training in either group of subjects. The "untrained" muscles were examined at rest, during two cycles of three grades of exercise, and in recovery. The flexor muscles of the athletes had higher concentrations of phosphocreatine and ATP than did those of the control subjects at rest and during exercise. The athletes' muscles possessed a higher capacity for generation of ATP by oxidative metabolism than did control subjects' muscles according to the following criteria: (i) high force output, 60% of maximum voluntary contraction, was more easily reached and better maintained in both exercise cycles; (ii) the ratio of inorganic phosphate to phosphocreatine rose less during exercise and recovered faster in the postexercise period; (iii) there was no loss of adenine nucleotides or total phosphate from the athletes' muscles but significant losses from the control subjects' muscles; and (iv) the pH decreased no more than 0.1 unit in the athletes' muscles during exercise, attesting to a relatively slow glycolysis and/or a rapid oxidation of lactate. In the muscles of the control subjects, on the other hand, the pH decreased nearly 0.4 unit early in the first exercise cycle, indicating a relatively fast glycolysis and/or slower oxidation of lactate. In the second exercise cycle, the pH returned to near normal in the control subjects' muscles, reflecting diminished lactate formation because of glycogen depletion and lactate washout by the high blood flow induced by exercise. By the end of the exercise program, the maximum voluntary contractile force for the control subjects had declined to less than 60% of the initial value. This decline could be explained best by exhaustion of the glycolytic contribution to muscle contraction. Therefore, the residual maximum strength provided a measure of the oxidative capacity to support contraction, as is discussed. In conclusion, we suggest that a greater oxidative capacity relative to glycolytic capacity for support of contraction in untrained muscle of world-class runners reflects a genetic endowment for physical endurance. Additional systemic effects of training cannot be completely excluded. 31P magnetic resonance spectroscopy provides a noninvasive method for assessing this endowment.

Adenine Nucleotides↗
PubMed1988

Non-invasive evaluation of malignant hyperthermia susceptibility with phosphorus nuclear magnetic resonance spectroscopy.

Using in vivo 31P NMR spectroscopy, the authors compared the NMR spectra of the flexor muscles of the forearm from 13 humans characterized as MH susceptible on the basis of in vitro caffeine/halothane contracture tests with those from 25 normal controls. The levels of phosphocreatine (PCr), inorganic phosphate (Pi), and ATP during rest, graded exercise, and post-exercise recovery were measured in their forearms. MH susceptible subjects had significantly (P less than 0.001) higher Pi/PCr values (0.222 +/- 0.009) at rest than did normal controls (0.140 +/- 0.004). In addition, a significantly (P less than 0.01) slower post-exercise recovery rate was found in the MH-susceptible group. There was no significant difference between the two groups in the relationship of work rate to Pi/PCr. These data suggest that unchallenged MH susceptible patients can be distinguished from normals using 31P NMR spectroscopy. The potential use of this technique as a non-invasive tool in determining MH susceptibility is discussed, as well as the possible mechanisms underlying the observed 31P NMR abnormalities.

Adenosine Triphosphate↗
PubMed1988

Optical and nuclear magnetic resonance studies of hypoxia in human tissue and tumors.

Correlations of energy state with response to therapy are more difficult to analyze because of the large effect of tumor clearing and oxygenation upon the tumor energy state as detected by PMRS alone. The combination of time-resolved hemoglobinometry using picosecond laser technology and localized PMRS seems appropriate to unravel the complexities of therapeutic intervention, tumor energetics, and oxygenation.

Energy Metabolism↗
PubMed1988

Mitochondrial function in normal and genetically altered cells and tissues.

The impact upon oxidative metabolism of normal and pathological variations of oxidative capability is just beginning to be understood, based upon the few examples of human and animal subject survivals and the relatively few cell systems in which the impact of molecular pathologies on function has been studied. On the one hand, difficulties of isolation of systems containing altered oxidases are significant because of ineffective assembly or small amounts of surviving isoenzymes, and on the other hand, unexpected fragilities of the oxidase system may lead to low yields when subjected to the preparative stresses appropriate to the wild types. To circumvent these problems, this paper describes the application, in vivo, of noninvasive, nondestructive techniques to study the function of cytochrome oxidase and other components of the respiratory chain, particularly cytochromes b-c1 in human subjects on the one hand, and in isolated cells on the other, principally mutants of Saccharomyces cerevisiae in which the subunit content is varied. Two principal spectroscopic approaches are employed: optical and phosphorus magnetic resonance spectroscopy (P MRS). Optical spectroscopy of the near red region of the spectrum provides effective analysis of brain and muscle, as does the surface coil of space-resolved phosphorus magnetic resonance. Both techniques are applicable to suspensions of single cells such as yeast. The optical method yields essential information on oxygen delivery to tissues by hemoglobin and myoglobin and oxygen utilization by cytochrome oxidase. P MRS affords essential information on the efficiency of ATP generation and the extent to which oxidative metabolism meets the needs of cell function in terms of the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). This in turn enables the calculation of the velocity of oxidative metabolism, V, in relation to its maximum capability, Vm, according to a Michaelis-Menten relationship that involves control not only by ADP (Pi/PCr) and Pi, but also by oxygen and substrate deliveries. Thus, an overview of the functionality of mitochondria in cells and tissues is uniquely provided by this combined approach and thereby deficiencies of components of the respiratory chain are quantified.

Adenosine Triphosphate↗
PubMed1988

In vivo 31P-NMR spectroscopy of chronically stimulated canine skeletal muscle.

Chronic stimulation converts skeletal muscle of mixed fiber type to a uniform muscle made up of type I, fatigue-resistant fibers. Here, the bioenergetic correlates of fatigue resistance in conditioned canine latissimus dorsi are assessed with in vivo phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. After chronic electrical stimulation, five dogs underwent 31P-NMR spectroscopic and isometric tension measurements on conditioned and contralateral control muscle during stimulation for 200, 300, 500, and 800 ms of an 1,100-ms duty cycle. With stimulation, phosphocreatine (PCr) fell proportional to the degree of stimulation in both conditioned and control muscle but fell significantly less in conditioned muscle at all but the least intense stimulation period (200 ms). Isometric tension, expressed as a tension time index per gram muscle, was significantly greater in the conditioned muscle at the two longest stimulation periods. The overall small change in PCr and the lack of a plateau in tension observed in the conditioned muscle are similar to that seen in cardiac muscle during increased energy demand. This study indicates that the conditioned muscle's markedly enhanced resistance to fatigue is in part the result of its increased capacity for oxidative phosphorylation.

Animals↗
PubMed1988

Correlated in vivo 31P-NMR and NADH fluorometric studies on gerbil brain in graded hypoxia and hyperoxia.

Mitochondrial energy coupling in the gerbil brain was characterized by the relationship between intracellular phosphocreatine (PCr)/inorganic phosphate (Pi), phosphorylation ratio, and the mitochondrial redox state in graded hypoxia. Phosphorus-nuclear magnetic resonance (NMR) spectra of the brain and whole head were taken by surface and saddle coil, respectively. The NADH level of the brain cortex was monitored by in vivo fluororeflectometry. The PCr and Pi of the head and brain did not change between 100 and 10% O2 inhalation. PCr progressively decreased and Pi progressively increased with 6 and 4% 0% inhalation in the head. The PCr/Pi of the brain decreased by 44% at 6% fraction of inhaled oxygen (FIO2) and 57% at 4% FIO2. The ATP level did not change during hypoxia. The calculated phosphorylation ratio of the brain ([PCr] Kck[H+]/[Cr][Pi]) = ([ATP]/[ADP][Pi]) was 4.1 X 10(4) M-1 in normoxia. Hypoxia of increasing severity induced increasing NAD reduction of the brain cortex with 17% NAD reduction at 10% FIO2 when there was no change in phosphorylation ratio. The phosphorylation ratio decreased, i.e., the mitochondria failed to maintain the energy level of the brain when the magnitude of the change in NAD reduction to hypoxia was half of the total redox change between hyperoxia and anoxia. These studies demonstrated the feasibility of combined 31P-NMR and NADH fluorometry measurements on brain in vivo. The observations show similarities between the responses of mitochondrial oxidative phosphorylation to hypoxia in vivo and in vitro.

Algorithms↗
PubMed1988

Intracellular sodium flux and high-energy phosphorus metabolites in ischemic skeletal muscle.

We have employed concurrent 31P- and 23Na-nuclear magnetic resonance (NMR) spectroscopy in conjunction with the paramagnetic shift reagents dysprosium-chelated tripolyphosphate and triethylenetetramine-hexa-acetic acid to observe the intracellular sodium and phosphorus signals in rat leg muscle. With induced ischemia in the leg, we find slowly falling phosphorylation potential. At a critical value of, associated with energetic failure of the Na+-K+ antiport, the intracellular sodium signal begins to increase. We find the following critical values: log, 3.12 +/- 0.32; pH, 6.86 +/- 0.13; Na+ influx with and without ouabain, 5.1 +/- 4.3 and 4.0 +/- 1.3 mol.l-1.h-1, respectively.

Adenine Nucleotides↗