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P Styles

Publications and source records attributed to P Styles.

90 records · Page 5Linked to original sources
PubMed1986

Energetics of human muscle: exercise-induced ATP depletion.

The energetics of human muscle have been investigated in vivo during and after fatiguing aerobic, dynamic exercise. Changes in cytoplasmic pH and concentrations of phosphocreatine, ATP and Pi were followed using 31P nuclear magnetic resonance spectroscopy. ATP was significantly depleted in 6 out of 12 experiments and in these 6 experiments decreased to 55 +/- 5% of the pre-exercise concentration. Depleted muscle had a lower phosphocreatine concentration (17 +/- 5% of resting value) and lower pH (6.12 +/- 0.04) than fatigued muscle in which ATP loss was not observed (26 +/- 5% for phosphocreatine and 6.37 +/- 0.09 for pH). The free energy of hydrolysis of ATP was not significantly different in the two groups and was also similar in exhausted and nonexhausted muscle. Loss of ATP was associated with altered recovery of the muscle: [phosphocreatine], [Pi], and pH returned more slowly to their pre-exercise values and the initial rate of oxidative phosphorylation was diminished. The restitution of [ATP] to its pre-exercise value was much slower than that of the other metabolites.

Adenosine Diphosphate↗
PubMed1986

Are quenches dangerous?

There exists some uncertainty about the hazards which the quenching of a superconducting magnet would present to a subject undergoing an NMR examination. To investigate this problem, a 1.6-T whole-body magnet was quenched with an anesthetized pig lying in the bore. This paper reports our findings which, in the circumstances of this experiment, suggest that the risks are small.

Animals↗
PubMed1985

A method for localizing high-resolution NMR spectra from human subjects.

Several methods are available for the localization of high-resolution spectra. When the sample is a human subject, it may be difficult to realize a viable experimental protocol because the size and geometry of the subject often conflict with efficient probe design. In this paper a spectroscopic localization method is described which is based on the method of rotating frame imaging. A novel surface-coil probe has been developed so that this experiment can be performed on a large sample. 31P spectra from the thorax of a human subject are presented in which signals from liver and intercostal muscle are resolved. These data demonstrate that spatially resolved spectra of metabolites in vivo may be obtained in a time that is acceptable for patient examination.

Humans↗
PubMed1985

A mitochondrial encephalomyopathy. A combined 31P magnetic resonance and biochemical investigation.

A 15-year-old girl presented with recurrent encephalopathic episodes, epilepsy, myopathy and chronic lactic acidosis. A muscle biopsy revealed the presence of ragged red fibres and mitochondria with paracrystalline inclusions. Biochemical studies on freshly isolated skeletal muscle mitochondria demonstrated a deficiency of NADH-CoQ reductase activity. Investigation of her gastrocnemius muscle at rest by phosphorus nuclear magnetic resonance displayed a reduced phosphocreatine concentration with elevated levels of inorganic phosphate and ADP. Abnormalities were also apparent in her brain spectrum. It is therefore possible that the mitochondrial defect present in skeletal muscle is also being expressed in the brain.

Adolescent↗
PubMed1984

Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. A 31P nuclear magnetic resonance study.

A patient with prolonged post-viral exhaustion and excessive fatigue was examined by 31P nuclear magnetic resonance. During exercise, muscles of the forearm demonstrated abnormally early intracellular acidosis for the exercise performed. This was out of proportion to the associated changes in high-energy phosphates. This may represent excessive lactic acid formation resulting from a disorder of metabolic regulation. The metabolic abnormality in this patient could not have been demonstrated by traditional diagnostic techniques.

Adenosine Diphosphate↗
PubMed1984

Examination of the energetics of aging skeletal muscle using nuclear magnetic resonance.

Human skeletal muscle has been studied in vivo by 31P nuclear magnetic resonance. Young adult subjects were compared with healthy elderly subjects aged 70-80 years. Intracellular pH and concentrations of adenosine triphosphate (ATP), phosphocreatine and inorganic phosphate were measured. At rest, no differences were found between the two age groups. Aerobic dynamic exercise resulted in a similar reduction of phosphocreatine in both groups while the ATP concentration did not change. The pH fall in exercise was not significantly different in the elderly and younger subjects. The time to resynthesize ATP in the recovery period as measured by the time to replete phosphocreatine was also not different in the two groups. The results suggest that the aging process does not affect the metabolic ability of human skeletal muscle to respond to exercise and that changes found in muscle of the elderly are not due to alterations in energy production.

Adenosine Triphosphate↗
PubMed1983

Bioenergetics of intact human muscle. A 31P nuclear magnetic resonance study.

The metabolic state of human muscle in various functional states has been investigated by the non-invasive technique of 31P nuclear magnetic resonance. The concentrations of phosphocreatine, ATP and inorganic phosphate as well as intracellular pH in the flexor digitorum superficialis have been measured during rest, dynamic exercise and recovery from exercise. The observed relationship between phosphocreatine utilization and decrease in intracellular pH during aerobic exercise indicates that lactate production only becomes significant after more than 60% of the phosphocreatine is used up. Surprisingly intracellular pH may reach as low a value as 5.9 to 6.1, indicating that phosphofructokinase is still partially active at pH 6.0. There is no metabolic recovery if the muscle is made ischaemic following exercise, implying that glycolysis is switched off as soon as exercise is stopped. Lactic acidosis is not the cause of this and presumably Ca2+ is needed to maintain the activation of phosphorylase kinase. The time-course of phosphocreatine recovery after exercise reflects the rate of oxidative metabolism, while pH recovery probably represents H+ ion export from the muscle cell. The dynamics of metabolic changes can now be observed with a time resolution of 10 to 60 seconds and thus disturbances in energy metabolism can be readily detected in several pathological states.

Adenosine Diphosphate↗
PubMed1982

Nuclear magnetic resonance studies of forearm muscle in Duchenne dystrophy.

The forearms of six patients with Duchenne dystrophy were examined by the painless and non-invasive technique of high-resolution nuclear magnetic resonance spectroscopy. The phosphorus spectrum was abnormal in that the ratios of phosphocreatine to adenosine triphosphate and to inorganic phosphate were reduced. Absolute quantification under the conditions of this experiment was not possible but it was probable that in dystrophy the concentration of phosphocreatine in muscle was appreciably reduced. A signal in the phosphodiester region of the spectrum was recorded consistently in patients with dystrophy but not in controls. The intracellular pH of the muscle in the dystrophic patients was abnormally alkaline. The clinical application of nuclear magnetic resonance spectroscopy remains to be proved, but it appears to be a promising non-invasive technique for investigating biochemical abnormalities of muscle disease.

Adenosine Triphosphate↗
PubMed1982

Preliminary observations on the metabolic responses to exercise in humans, using 31-phosphorus nuclear magnetic resonance.

The new non-invasive method of 31P nuclear magnetic resonance (NMR) has been applied for the first time to human muscle. The metabolic response to exercise--a fall in intracellular pH, a fall in phosphocreatine content, and an increase in inorganic phosphate (Pi) content--occurs without any change in ATP content of the exercised muscle. Abnormal spectra occur in two myopathies examined to date: in McArdle's syndrome, pH rises during exercise, in contrast to the normal fall; and, in an unusual mitochondrial myopathy, Pi content is high, relative to phosphocreatine content, and in keeping with an excessive oxygen consumption in this patient. Intracellular pH reflected, in addition, the systemic pH of the subject; the anticipated abnormalities in muscle pH have been observed in association with lactic acidosis, renal failure and hyperventilation.

Acidosis, Respiratory↗
PubMed1981

Examination of a myopathy by phosphorus nuclear magnetic resonance.

A 16-year-old boy with myopathy, ophthalmoplegia, and raised basal metabolic rate was examined by the non-invasive technique of phosphorus-31 nuclear magnetic resonance (31 P NMR). The muscles of the forearm showed an abnormal 31P NMR spectrum with a high inorganic phosphate (Pi) content in relation to phosphocreatine (PCr) (PCr/Pi = 4; control = 10). This finding was compatible with the abnormality of mitochondrial function already established by biopsy and offers in addition an explanation for the raised oxygen consumption in this patient. The method of 31P NMR is suited to rapid non-invasive diagnosis in various muscle disorders.

Acidosis↗
PubMed1980

Localization of metabolites in animals using 31P topical magnetic resonance.

High-resolution phosphorous (31P)-NMR spectra of biological molecules provide detailed information about the metabolism of living systems. Although the NMR method is non-destructive, all studies so far, with two exceptions, have been carried out on excised, perfused organs and tissues or have required some form of surgery for in situ measurements. The use of 'surface' radiofrequency coils does not require surgery, but is best suited for tissues close to the surface of the animals. We describe here 'topical magnetic resonance'--a new, non-surgical method for acquiring 31P-NMR spectra from a selected, localized place deep within an animal by modifying the main magnetic field, B0, using only static-field gradients. The method is conceptually similar to one spin-imaging method but primarily provides biochemical rather than spatial information. This new technique can be used in fundamental investigations into living systems, clinical diagnosis and the estimation of the efficacy of drug therapy.

Adenosine Triphosphate↗
PubMedDate not supplied

The production, buffering and efflux of protons in human skeletal muscle during exercise and recovery.

We show how quantitative information about proton handling in human skeletal muscle in exercise and recovery can be obtained by 31P MRS and illustrate this with data from metabolic disorders. Proton production, proton efflux and passive buffering can be distinguished by comparing changes in [phosphocreatine] and pH at the end of exercise and by calculating ATP turnover during ischaemic exercise and in the 'natural experiment' of myophosphorylase deficiency (McArdle's disease). We calculate the effective buffer capacity to be 20-30 mmol/L/pH unit (slykes), somewhat lower than published measurements made in vitro but similar to other values obtained in vivo. This analysis is applied to data from normal muscle and a variety of disease states to estimate proton efflux during recovery and ATP production during exercise: (i) proton efflux during recovery is pH-dependent, reaching a 10 mmol/L/min at pH 6.2, and is increased in some cases of mitochondrial myopathy and in hypertension; (ii) glycogenolytic ATP production during exercise can reach 25 mmol/L/min in normal muscle and correlates approximately with [Pi] at the start of aerobic exercise and throughout ischaemic exercise; (iii) oxidative ATP production can reach 20-25 mmol/L/min and (as during recovery) correlates approximately with [Pi].

Adenosine Triphosphate↗
PubMedDate not supplied

Quantitative analysis by 31P magnetic resonance spectroscopy of abnormal mitochondrial oxidation in skeletal muscle during recovery from exercise.

We use the hyperbolic relationship between cytosolic [ADP] and the rate of phosphocreatine (PCr) resynthesis after exercise to estimate the apparent maximum rate of oxidative ATP synthesis (QMAX). We examine data from some human diseases in which mitochondrial oxidation may be impaired (due to reduced mitochondrial numbers, intrinsic mitochondrial defect or impaired vascular supply). Muscle responds to impaired oxidation by stimulating anaerobic ATP synthesis and/or by increasing [ADP], the stimulus to the mitochondrion. However, these responses interact: [ADP] depends on pH and [PCr], and lactic acid production tends to lower [ADP] (by lowering pH), while proton efflux has the opposite effect. We identify four patterns of results: (A) in mitochondrial myopathy, apparent QMAX is reduced and [ADP] is appropriately increased, because increased proton efflux reduces the pH change in exercise despite increased lactic acid production; (B) in some conditions (e.g., cyanotic congenital heart disease) apparent QMAX is reduced but there is no compensatory rise in [ADP], probably because anaerobic ATP synthesis during exercise is increased without increase in proton efflux; (C) in other conditions (e.g., myotonic dystrophy) [ADP] is increased during exercise but apparent QMAX is normal, suggesting either an increase in proton efflux and/or decrease in anaerobic ATP synthesis during exercise; (D) there are also conditions (e.g., respiratory failure) where, despite impaired oxygen supply, both apparent QMAX and end-exercise [ADP] are normal. We also discuss the metabolic conditions under which end-exercise [ADP] is increased by a mitochondrial defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗