ABSTRACT
The aim of our study was to investigate the contribution of physical deconditioning in skeletal muscle metabolic abnormalities in patients with chronic heart failure (CHF). Phosphate metabolism was studied in the leg muscle at rest and during exercise by using phosphate 31 nuclear magnetic resonance spectroscopy in a group of 14 patients with New York Heart Association class II and III CHF and left ventricular ejection fraction <40% and in two groups of age-matched healthy volunteers: one group of 7 sedentary and another of 7 trained subjects. Phosphocreatine depletion rate, intracellular pH, and adenosine diphosphate levels in the muscle during exercise were not statistically different in the CHF patients and in the sedentary healthy subjects, but both groups were statistically different from the trained healthy subjects, who had slower phosphocreatine depletion rates, as well as less intracellular acidosis and lower adenosine diphosphate levels during exercise (p = 0.02; analysis of variance). Our results suggest that metabolic changes occurring in the skeletal muscle of patients with CHF may contribute to the limitation of exercise capacity and are most likely to be a consequence of physical deconditioning because they are very similar to what is observed in sedentary and otherwise healthy subjects as compared with trained subjects.
Subject(s)
Cardiovascular Deconditioning , Heart Failure/metabolism , Muscle, Skeletal/metabolism , Phosphates/metabolism , Adult , Aged , Exercise Test , Female , Humans , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy/instrumentation , Magnetic Resonance Spectroscopy/methods , Male , Middle AgedABSTRACT
We studied skeletal muscle phosphate metabolism abnormalities to examine their contribution at an early stage of congestive heart failure (CHF) in rats with aortocaval fistula (ACF) 4 wk after the procedure. In a group of 26 rats (13 with ACF and 13 sham operated), we assessed the degree of CHF. The ACF produced a significant rise in heart weight and plasma atrial natriuretic peptide. In a second group of 26 rats (13 ACF and 13 sham operated), we performed 31P-magnetic resonance spectroscopy in the gastrocnemius muscle during motor activity produced by electrical stimulation. The rate of phosphocreatine depletion, expressed by its initial slope, was higher in the ACF rats compared with controls (0.078 +/- 0.01 vs. 0.041 +/- 0.007; P < 0.03). pH and ATP decreased and phosphodiesters increased in all rats during electrical stimulation, with no difference between ACF rats and controls. The kinetics of phosphocreatine recovery were not different between ACF rats and controls. Together with previous studies, our present results suggest that muscle metabolism abnormalities in CHF may vary according to the experimental model and may be observed early in the course of the disease.
Subject(s)
Blood Volume , Heart Failure/metabolism , Muscle, Skeletal/metabolism , Phosphates/metabolism , Adenosine Triphosphate/metabolism , Animals , Aorta, Abdominal , Arteriovenous Shunt, Surgical , Electric Stimulation , Heart Failure/etiology , Hemodynamics , Hydrogen-Ion Concentration , Kinetics , Magnetic Resonance Spectroscopy , Male , Motor Activity , Phosphocreatine/metabolism , Rats , Rats, Wistar , Vena Cava, Inferior/surgeryABSTRACT
Several studies of phosphorus 31 (31P) magnetic resonance spectroscopy (MRS) have demonstrated the presence of skeletal muscle metabolic abnormalities during exercise in patients with chronic heart failure (CHF). We studied the contribution of these abnormalities to the limitation of exercise capacity in CHF. In 25 patients (age 57 +/- 2 years, left ventricular ejection fraction [LVEF] 28% +/- 1.6%, peak oxygen consumption (VO2) 16 +/- 1.2 ml/kg/mm) (mean +/- SEM), we studied the calf muscle at rest and during plantar flexion with 31P MRS. The phosphocreatine (PCr) depletion rate was significantly negatively correlated to peak VO2 (r = -0.62, p = 0.001) but not to LVEF. Muscle pH was correlated with the inorganic phosphorus (Pi)/PCr ratio (r = -0.69, p = 0.0001) and with the PCr/adenosine triphosphate beta (ATP beta) ratio (which negatively relates to adenosine diphosphate [ADP] concentration) (r = 0.65, p = 0.00001). Although muscle ATP (ATP/sum of phosphorus [sigma P] remained stable, in 8 patients ATP/sigma P decreased significantly (-15% +/- 4%, p = 0.0002). In this ATP-depleted group, peak VO2 was significantly lower than that of the nondepleted group and PCr depletion more rapid, whereas LVEF did not differ. Skeletal muscle metabolic abnormalities in CHF contribute markedly to the alteration of exercise capacity. Rapid PCr depletion and muscle acidosis are the most relevant abnormalities. ATP depletion and excessive increase in ADP during exercise may contribute further to exercise limitation specifically in patients with more marked CHF.
Subject(s)
Heart Failure/metabolism , Magnetic Resonance Spectroscopy , Muscle, Skeletal/metabolism , Phosphocreatine/metabolism , Physical Exertion , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Adult , Aged , Analysis of Variance , Female , Heart Failure/physiopathology , Humans , Male , Middle Aged , Oxygen Consumption , Stroke VolumeABSTRACT
The effects of HCO3Na load on acid-base balance and muscle intracellular bioenergetics have been investigated using 31P-magnetic resonance spectroscopy in an experimental model of endotoxinic shock. Anesthetized, mechanically ventilated, and paralyzed rats (n = 16) were given an intravenous bolus of Escherichia coli lipopolysaccharide (15 mg/kg). When shock was established they were randomly assigned to receive either HCO3Na intravenously (2 mmol/kg in 2 min) or an equimolar saline injection. Lipopolysaccharide induced a significant decrease in the levels of mean arterial pressure (58 +/- 6 vs. 120 +/- 8 mmHg), arterial pH (7.20 +/- .03 vs. 7.35 +/- .01), intracellular pH (6.86 +/- .04 vs. 7.08 +/- .01), a marked hyperlactatemia (7 +/- 3 vs. 1.2 +/- .2 mmol/L) and a drop in the phosphocreatine-inorganic phosphate ratio. In the bicarbonate-loaded rats, mean arterial pressure further decreased whereas it remained unchanged in the saline group. Bicarbonate increased arterial pH and PaCO2 transiently. In the saline group, arterial pH decreased and PaCO2 remained stable. In both groups, intracellular pH and high energy phosphates had a similar evolution. In this model of septic shock, partial correction of arterial pH using HCO3Na did not reduce the metabolic cellular injury in skeletal muscle. Based on these results, HCO3Na may be of limited therapeutic value in severe septic metabolic acidosis.
Subject(s)
Muscle, Skeletal/metabolism , Shock, Septic/metabolism , Sodium Bicarbonate/pharmacology , Acidosis, Lactic/chemically induced , Acidosis, Lactic/complications , Acidosis, Lactic/physiopathology , Animals , Blood Pressure/drug effects , Disease Models, Animal , Hindlimb , Hydrogen-Ion Concentration , Lipopolysaccharides/pharmacology , Magnetic Resonance Spectroscopy , Muscle, Skeletal/drug effects , Physical Phenomena , Physics , Rats , Rats, Sprague-Dawley , Sodium Chloride/pharmacologyABSTRACT
To test the hypothesis of muscle bioenergetic impairment in potassium depletion, chronic potassium-depleted rats and pair-fed control rats were studied with phosphorus 31 nuclear magnetic resonance measurements of leg muscle intracellular pH, phosphocreatine, inorganic phosphate, and adenosine triphosphate at rest and during maximal nontetanic stimulation, 48 hours after a swimming test. The potassium-depleted rats exhibited a significant hypokalemia, a metabolic extracellular alkalosis, and an intracellular acidosis. Their physical endurance was markedly reduced, and they displayed higher plasma creatine kinase levels than the control group. However, the phosphocreatine/inorganic phosphate ratio, which is a measure of the energy reserve of the cell, was similar in both groups at rest and during electrical stimulation and subsequent recovery. Resting muscle glycogen and relative intracellular acidification during stimulation did not differ in the two groups, arguing against an impairment of anaerobic metabolism in potassium depletion. These results indicate that the energy availability of muscle cell is unchanged during potassium deficiency.
Subject(s)
Energy Metabolism , Muscles/metabolism , Potassium Deficiency/metabolism , Animals , Creatine Kinase/blood , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Male , Phosphates/analysis , Phosphocreatine/analysis , Rats , Rats, WistarABSTRACT
The thenar muscles and gastrocnemius of a patient with myotonic dystrophy were investigated, at rest, by phosphorus nuclear magnetic resonance spectroscopy. A decrease in phosphocreatine level and an increase in inorganic phosphate and phosphodiester levels were found in the gastrocnemius, which was clinically spared, whilst the thenar muscles, which were wasted and affected by myotonia, exhibited only an increased inorganic phosphate level and an elevated pH. These findings were comparable with those found in other muscular disorders, such as Duchenne's and Becker's dystrophies, as well as in limb girdle dystrophy. They suggested that the abnormalities observed were unrelated to myotonia or wasting, and the possibility of a secondary mitochondrial disorder in myotonic dystrophy, is to be considered.
Subject(s)
Energy Metabolism , Myotonic Dystrophy/metabolism , Adult , Humans , Magnetic Resonance Spectroscopy , Male , Mitochondria, Muscle/metabolism , Muscles/metabolism , PhosphorusABSTRACT
Two cases of polymyositis were followed using phosphorus nuclear magnetic resonance spectroscopy. The spectra recorded during remission were normal, but those collected from the gastrocnemius muscle during the active phase of the diseases showed an increased inorganic phosphate level or a decreased phosphocreatine content. The intracellular pH was normal. These findings may be related to an impairement in mitochondrial metabolism secondary to the inflammatory process. Moreover, the fact that the abnormalities observed disappeared after treatment suggests that phosphorus NMR spectroscopy could be used as a non-invasive method in the follow-up of polymyositis, but this must be confirmed by further studies.
Subject(s)
Dermatomyositis/metabolism , Mitochondrial Myopathies/metabolism , Polymyositis/metabolism , Adenosine Triphosphate/analysis , Adenosine Triphosphate/metabolism , Dermatomyositis/complications , Dermatomyositis/diagnostic imaging , Female , Humans , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Male , Middle Aged , Mitochondrial Myopathies/diagnostic imaging , Mitochondrial Myopathies/etiology , Phosphocreatine/analysis , Phosphocreatine/metabolism , Phosphorus/analysis , Phosphorus/metabolism , Polymyositis/complications , Polymyositis/diagnostic imaging , RadiographyABSTRACT
To examine the respective roles of malnutrition and phosphate depletion on muscle exercise capacity and bioenergetics, phosphate-depleted, either underfed or partly refed rats; phosphate-supplemented, either underfed or partly refed rats; and well-nourished control animals were studied, using swim time to exhaustion and 31P NMR spectroscopy measurements of muscle phosphocreatine, inorganic phosphate, adenosine triphosphate and intracellular pH. Only partly refed rats displayed hypophosphataemia. Swim time to exhaustion was lower in non-refed rats than in controls. Among the four groups, both refeeding and phosphate depletion positively affected swim time to exhaustion (both with P less than 0.02), and swim time to exhaustion was negatively correlated with phosphataemia (P less than 0.05). At rest, the ratio of muscle phosphocreatine/inorganic phosphate was lower in the phosphate-supplemented rats than in controls, whereas muscle phosphocreatine/adenosine triphosphate and intracellular pH were comparable. After non-tetanic stimulation, the muscle phosphocreatine recovery was slower in the four groups than in controls and closely correlated with exhaustion (P less than 0.01). These findings suggest that malnutrition alters the capacity of muscular work, mainly because of a reduced cell oxidative energy availability. These patterns are improved by partial refeeding and clearly influenced by the level of phosphorus intake, whether depletion is capable of improving metabolic alterations or uncontrolled supplementation is deleterious in malnourished animals.
Subject(s)
Glucose/administration & dosage , Muscles/metabolism , Nutrition Disorders/complications , Phosphates/deficiency , Physical Exertion/physiology , Animals , Male , Rats , Rats, Inbred Strains , SwimmingABSTRACT
Phosphorus nuclear magnetic resonance spectroscopy was used to investigate the muscle bioenergetics in different hypothyroid states. Using the thenar muscle group as reference, 2 patients with chronic and severe hormonal deficiency, 3 patients with subacute hypothyroidism, and 8 patients with moderate thyroid insufficiency with isolated high blood TSH levels were studied at rest, during exercise, and during subsequent recovery. The patients were compared with 15 control subjects. Only 1 patient presented a clinical myopathy. The intracellular pH and the relative measurements of inorganic phosphate, phosphocreatine, phosphodiesters, and ATP were directly calculated from phosphorus spectra. Resting muscle showed a significant rise in the inorganic phosphate to ATP ratio. In working hypothyroid muscle, a more important decrease in phosphocreatine levels was noted in patients with chronic and subacute thyroid deficiency, while the intracellular pH fall was greater in all hypothyroid patients than in control subjects. The phosphocreatine recovery rate was lower in all deficient patients, reflecting a probable mitochondrial metabolism impairment. These results are consistent with a defect of the high energy phosphate metabolism in hypothyroidism, even in moderate or recent hormonal deficiency.
Subject(s)
Energy Metabolism , Hypothyroidism/metabolism , Magnetic Resonance Spectroscopy , Muscles/metabolism , Adenosine Triphosphate/metabolism , Adult , Aged , Esters/metabolism , Exercise , Female , Humans , Middle Aged , Phosphates/metabolism , Phosphocreatine/metabolism , PhosphorusABSTRACT
Using phosphorus nuclear magnetic resonance spectroscopy, this study was undertaken to determine the effects of experimental hypothyroidism on muscle bioenergetics. The peaks of phosphocreatine (PCr), Pi, phosphodiesters (PDE), sugar phosphomonoesters, and ATP were obtained at rest, during a 2-Hz hindleg muscle stimulation, and during a subsequent recovery period from four groups of anesthetized rats as follows: one control and three hypothyroid (HT) groups treated by propylthyouracil during 2, 4, and 6 wk, respectively. Resting spectra showed a significant rise in Pi by 30% and decreased intracellular pH and PCr/Pi in all three HT groups. PDE progressively increased to 200% of its initial value with hypothyroidism duration. Muscle stimulation did not lead to significant differences in PCr depletion. The percentage of PCr recovery is less in HT muscle than in control muscle. An abnormal H+ metabolism is obvious in all three HT groups. These results indicate abnormal bioenergetics in HT muscle and suggest an impairment of mitochondrial metabolism and of the H+ efflux. They also evoke a high sensitivity of cellular energetics to thyroid deficiency.
Subject(s)
Hypothyroidism/metabolism , Muscles/metabolism , Animals , Body Weight , Hindlimb , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Male , Rats , Rats, Inbred Strains , Thyroid Hormones/metabolismABSTRACT
Phosphorus nuclear magnetic resonance spectroscopy enables the energy metabolism of skeletal muscles to be studied non-invasively in vivo. Relative concentrations of phosphocreatine (PCr), inorganic phosphate (iP), monophosphoric sugars (mP) and ATP, as well as intracellular pH values, are directly accessible through the spectra. The striated muscle is continuously studied at rest, during exercise and during recovery. Exercise-induced changes in pH and mP provide indirect information on glycogenolysis and glycolysis. The speed of PCr resynthesis during post-exercise recovery and the PCr/iP ratio values at rest excellently reflect mitochondrial oxidative phosphorylations. Phosphorus NMR spectroscopy therefore is of interest not only to study the impact, through hypoxia, on muscle energy metabolism of such pathologies as cardiac or respiratory failure, or to study various acquired metabolic muscular diseases, but also and above all, to detect and locate muscular enzyme deficiencies involving glycogenolysis, glycolysis or mitochondrial metabolism, thereby pointing to the diagnosis of congenital, and mainly metabolic, myopathies.
Subject(s)
Magnetic Resonance Spectroscopy , Muscles/metabolism , Phosphorus/analysis , Energy Metabolism/physiology , Humans , Magnetic Resonance Spectroscopy/methods , Muscular Diseases/diagnosis , Muscular Diseases/metabolismABSTRACT
Phosphorus nuclear magnetic resonance spectroscopy was used to investigate muscle bioenergetics in 9 hyperthyroid patients who were compared with 9 normal subjects. Using the thenar muscle group as reference, the inorganic phosphate, phosphocreatine and intracellular pH were calculated at rest, during aerobic exercise (0.13 w) and post-exercise recovery. No difference was found at rest. After 5 min of exercise, the hyperthyroid patients exhibited a more important phosphocreatine depletion (41.2 +/- 8.2 vs 31.1% +/- 6.5, p less than 0.02) and a larger pH fall (6.65 +/- 0.04 vs 7.01 +/- 0.10, p less than 0.001) than the control subjects. The phosphocreatine recovery rate was not significantly different in hyperthyroid patients and control subjects. These results suggest that exercise requires more ATP in hyperthyroid patients than in normal subjects and that there is excessive dependence on glycolytic metabolism for ATP synthesis in hyperthyroidism. Phosphocreatine resynthesis, reflecting the oxidative metabolism, is not increased. These metabolic disturbances could also supply a partial explanation to the frequent exercise intolerance in hyperthyroid patients.
Subject(s)
Energy Metabolism , Hyperthyroidism/metabolism , Muscles/metabolism , Adenosine Triphosphate/biosynthesis , Adult , Aged , Exercise , Female , Humans , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Male , Middle Aged , Phosphates/analysis , Phosphocreatine/analysis , Phosphorus IsotopesABSTRACT
From a series of standard SE imaging sequences, performed on a Bruker 0.28 T imaging system, with the assistance of a healthy volunteer, the image signal-to-noise (S/N) ratio obtained from a 23-cm square surface coil has been shown to increase by up to 38% as the tube gauge is increased from 4 to 18 mm. The reason did not lie solely in the much improved Q factor of the unloaded coils. Despite a more than twofold increase in the unloaded Q factor, the loaded coil Q values only increased by 8%. It would appear, however, that the resistive, dielectric and inductive noise components are all reduced, and hence contribute to the observed improved S/N. The reduction in pure ohmic losses accounts for a quarter of the improved S/N, while the reduced inductive and dielectric losses provide the remaining three quarters. No independent quantification of the two latter noise sources was attempted, although a reduced dielectric contribution is confirmed qualitatively by a reduction in the negative frequency shift of the resonance frequency as a function of increasing coil gauge when the coil is loaded.
Subject(s)
Magnetic Resonance Imaging/instrumentation , Humans , Image Enhancement/methods , Magnetic Resonance Imaging/methodsABSTRACT
Pathophysiologic events leading to rhabdomyolysis in alcoholics are not clearly understood. We examined 18 alcoholic patients (10 with and 8 without a recent history of rhabdomyolysis) and 15 healthy non-alcoholic volunteers by phosphorus nuclear magnetic resonance spectroscopy of thenar eminence muscle. At rest, phosphocreatine, ATP, and pH levels were similar in patients and control subjects. During aerobic exercise, phosphocreatine utilization was greater, pH fell more slowly, and maximum acidosis was less in alcoholics with previous rhabdomyolysis than in control subjects. During ischemic exercise, both patient groups exhibited a significantly slower and smaller decrease in pH than did control subjects. These findings are consistent with impaired muscular glycolysis or glycogenolysis in both alcoholic groups. This metabolic myopathy may contribute to the onset of acute rhabdomyolsis.