Phosphocreatine Recovery Rate Research Articles

Phosphorus magnetic resonance spectroscopy in cluster headache.

We performed in vivo MR spectroscopy phosphorus (31P-MRS) on the brain and skeletal muscles of 14 patients affected with cluster headache (CH). We examined patients in interictal periods, and also examined nine of them during the cluster period, although not during the attack. Brain 31P-MRS showed reduced phosphocreatine (PCr) levels, an increased ADP concentration (calculated from the creatine kinase equilibrium), a reduced phosphorylation potential, and a high relative rate of ATP biosynthesis (V/Vmax %). The inorganic phosphate (P(i)) content was increased during the cluster period. Ten of 13 patients also showed a slow rate of PCr recovery in muscle after the exercise. 31P-MRS in CH patients showed abnormalities of brain and skeletal muscle energy metabolism comparable with those seen in various types of migraine, thus leading us to suggest a similarity in biochemical pathogenic mechanisms between CH and migraine.

The application of blood flow measurements to the study of aging muscle.

Blood flow to skeletal muscle is a potentially important factor in the reduction of muscle function associated with aging (sarcopenia). The main influence of reduced blood flow capacity on muscle function is in limiting oxidative metabolism. Direct measures of blood flow include: intravital-microscopy, plethysmography, radioactive microspheres, 133Xenon washout, thermodilution, and Doppler ultrasound. Indirect measurement of blood flow includes arm-to-ankle pressure index and the rate of phosphocreatine recovery after exercise. Several new methodologies have been developed to evaluate muscle blood flow, including color-Doppler imaging, magnetic resonance imaging/angiography (MRI/MRA), and near-infrared spectroscopy (NIRS). As adaptations of traditional techniques, these methods promise more precise information under less invasive conditions. MRI is an expensive and technically challenging method able to measure vessel location, blood flow, and wall diameter in blood vessels throughout the cardiac cycle. Color-Doppler provides excellent temporal resolution blood flow throughout the cardiac cycle, along with some anatomical information. NIRS is an inexpensive and portable technology that can measure changes in oxygen saturation and provide information on tissue oxygen delivery in studies of frailer and more difficult-to-study subjects. Muscle blood flow is not thought to limit oxidative metabolism under normal conditions in young individuals. However, it is not clear what happens to muscle blood flow in healthy older individuals. Reduced capillary density, less maximal blood flow, and a slower hyperemic flow response have been reported in some, but not all, studies. Further studies with the newer methodologies are needed to re-examine age-related changes in muscle blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Defective brain and muscle energy metabolism shown by in vivo 31 P magnetic resonance spectroscopy in nonaffected carriers of 11778 mtDNA mutation

In vivo phosphorus magnetic resonance spectroscopy (31P-MRS) showed defective brain and muscle energy metabolism in three affected siblings in a family with Leber's hereditary optic neuropathy (LHON) with the 11778 mtDNA mutation. We studied 14 nonaffected members of the same pedigree by 31P-MRS and molecular genetics. Nine of 14 individuals studied had the 11778 mtDNA mutation, with various degrees of heteroplasmy. A decreased brain energy reserve, as shown by low phosphocreatine content and phosphorylation potential and high [ADP], was present in eight of these nine subjects with the 11778 mutation. A low rate of postexercise phosphocreatine recovery in muscle was present in six of the nine mutated individuals. Normal MRS findings in the brain of one and the muscle of three carriers were accompanied by a low percentage of mutated mtDNA. All subjects without mutation had normal brain and muscle MRS. 31P-MRS disclosed defective bioenergetics in the brain or muscle or both of all asymptomatic carriers studied from our pedigree.

Relation of myocardial oxygen consumption and function to high energy phosphate utilization during graded hypoxia and reoxygenation in sheep in vivo.

This study investigates the relation between myocardial oxygen consumption (MVO2), function, and high energy phosphates during severe hypoxia and reoxygenation in sheep in vivo. Graded hypoxia was performed in open-chested sheep to adjust PO2 to values where rapid depletion of energy stores occurred. Highly time-resolved 31P nuclear magnetic resonance spectroscopy enabled monitoring of myocardial phosphates throughout hypoxia and recovery with simultaneous MVO2 measurement. Sheep undergoing graded hypoxia (n = 5) with an arterial PO2 nadir of 13.4 +/- 0.5 mmHg, demonstrated maintained rates of oxygen consumption with large changes in coronary flow as phosphocreatine (PCr) decreased within 4 min to 40 +/- 7% of baseline. ATP utilization rate increased simultaneously 59 +/- 20%. Recovery was accompanied by marked increases in MVO2 from 2.0 +/- 0.5 to 7.2 +/- 1.9 mumol/g per min, while PCr recovery rate was 4.3 +/- 0.6 mumol/g per min. ATP decreased to 75 +/- 6% of baseline during severe hypoxia and did not recover. Sheep (n = 5) which underwent moderate hypoxia (PO2 maintained 25-35 mmHg for 10 min) did not demonstrate change in PCr or ATP. Functional and work assessment (n = 4) revealed that cardiac power increased during the graded hypoxia and was maintained through early reoxygenation. These studies show that (a) MVO2 does not decrease during oxygen deprivation in vivo despite marked and rapid decreases in high energy phosphates; (b) contractile function during hypoxia in vivo does not decrease during periods of PCr depletion and intracellular phosphate accumulation, and this may be related to marked increases in circulating catecholamines during global hypoxia. The measured creatine rephosphorylation rate is 34 +/- 11% of predicted (P < 0.01) calculated from reoxygenation parameters, which indicates that some mitochondrial respiratory uncoupling also occurs during the rephosphorylation period.

Muscle 31P-NMR in a mitochondrial encephalomyelopathy due to a specific defect in pyruvate dehydrogenase

P31 NMR spectroscopy is useful for the diagnosis of some myopathies and it is necessary to further specify its range of application. Mitochondrial myopathies show one or more abnormalities, yielding a heterogeneity of results that may correspond to their biochemical heterogeneity. We here report on a rare mitochondrial disease due to a defect in the protein X of the pyruvate dehydrogenase complex. The abnormalities observed by muscle P31 NMR were mainly low phosphocreatine (PCr) and high inorganic phosphate at rest and too small acidification with exercise. The patient thus showed 2 of the main abnormalities described, alone or in association, in mitochondrial myopathies. The rate of PCr recovery was normal. P31 NMR thus seems sensitive in this precise defect and can help the clinician for the diagnostic process. It is however too early to conclude whether P31 NMR abnormalities are specific for precise mitochondrial defects. This search for diagnostic specificity could also benefit from other NMR approaches.

Metabolic abnormalities in skeletal muscle after myocardial infarction in the rat.

1. The effect of experimental myocardial infarction on exercise and recovery of rat skeletal muscle was studied using 31P n.m.r. 4 weeks post-operatively. 2. Myocardial infarction (12 +/- 3% of left ventricular volume), insufficient to produce haemodynamic manifestations of heart failure, was without significant effect on exercise bioenergetics of skeletal muscle. 3. Citrate synthase activity was reduced by 17% in the infarcted animals and there was a marked slowing of the rate of phosphocreatine recovery after infarction (half-time 0.7 +/- 0.1 min to 1.6 +/- 0.2 min) in the absence of evidence of left ventricular failure or hypertrophy. 4. The study of recovery bioenergetics could provide a more sensitive measure of mitochondrial function than exercise, where no bioenergetic abnormality was detected. 5. Myocardial infarction can produce evidence of mitochondrial abnormality in skeletal muscle in the absence of haemodynamic compromise.

31P-magnetic resonance spectroscopy in migraine without aura.

We investigated 22 patients with migraine without aura, all drug-free and in headache-free periods, by means of 31P-magnetic resonance spectroscopy (MRS) of brain and muscle. Brain 31P-MRS showed significantly low phosphocreatine, increased adenosine diphosphate, and decreased phosphorylation potential. There was a slow rate of phosphocreatine recovery after exercise in the muscle of 12 of 22 patients. Energy metabolism is abnormal in migraine without aura, as previously demonstrated in patients with migraine stroke and migraine with aura.

Control of phosphocreatine resynthesis during recovery from exercise in human skeletal muscle.

Information about the control of mitochondrial function in skeletal muscle in vivo can be obtained from the relationship between the rate of mitochondrial oxidation and the intracellular concentrations of phosphorus metabolites, although the analysis is complicated by the constraints imposed by the creatine kinase equilibrium. The rate of phosphocreatine (PCr) recovery after exercise measured by 31P MRS is an estimate of net oxidative ATP synthesis. Analysing such data from normal and abnormal human muscle, we show that the approximately exponential recovery kinetics of ADP and PCr imply that the rate of PCr resynthesis has a hyperbolic dependence on [ADP] but remains approximately linear with respect to the concentration of orthophosphate (Pi) and therefore also [PCr] and [creatine]. Both kinds of relationship are consistent with experimental data from exercising animal muscle and also with data from isolated mitochondria which suggest kinetic control of mitochondrial ATP synthesis of [ADP]. These relationships are altered in proven mitochondrial disease. This analysis offers a way to quantify mitochondrial function and its abnormalities in vivo.

Energetic metabolism in hypothyroid skeletal muscle, as studied by phosphorus magnetic resonance spectroscopy.

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.

Muscle bioenergetic impairment in hyperthyroid man: A study by 31P NMR spectroscopy

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.

Skeletal muscle metabolism in the leg during exercise in patients with congestive heart failure

1. Using 31P nuclear magnetic resonance, it has previously been demonstrated that patients with congestive heart failure exhibit a greater than normal phosphocreatine (PCr) depletion in the working skeletal muscles of the arm. We have studied the importance of the work necessary to reach a similar PCr depletion ([PCr]/([PCr] + [Pi]) = 0.5) in calf muscle. Our results show significantly lower values for patients with congestive heart failure in both aerobic and ischaemic conditions (respectively: 0.009 +/- 0.007 vs 0.026 +/- 0.013 W/kg body weight, P less than 0.01; 0.29 +/- 0.16 vs 0.90 +/- 0.25 J/kg body weight, P less than 0.01). 2. This original model of skeletal muscle exercise facilitates a comparison of PCr recovery rate due to a similarity in the PCr depletion and intracellular pH in the two series at the start of recovery. However, the PCr recovery rate is similar after both normoxic and ischaemic exercise, i.e. respective percentages of PCr increase in the first 25 s recovery spectrum were: (a) aerobic exercise, congestive heart failure 133 +/- 18%, control series 138 +/- 18%; (b) ischaemic exercise, congestive heart failure 114 +/- 13%, control series 118 +/- 12%. The absence of a difference in PCr recovery rate and the greater PCr depletion by ischaemic work in patients with congestive heart failure suggest modifications that cannot be explained by a reduced blood flow to the muscle. 3. When comparing the two series, intracellular pH evolved similarly in normoxia and ischaemia during both work and recovery. Thus, no increase in anaerobic glycolytic activity appears when equivalent PCr depletion has occurred.

Postischemic recovery rate of cerebral ATP, phosphocreatine, pH, and evoked potentials

We tested the hypotheses that after complete cerebral ischemia, first, rate of recovery of ATP, phosphocreatine (PCr), and intracellular pH (pHi) varies with ischemic duration and second, rate of metabolic recovery is a more sensitive predictor of consequent electrophysiological deficit than steady-state metabolic recovery. With the use of transient intracranial hypertension in anesthetized dogs, ischemic duration was set for either 3, 12, or 30 min, which depressed somatosensory-evoked potential (SEP) recovery amplitude by 30, 59, and 88%, respectively. In contrast, ATP, PCr, and pHi, measured by 31P magnetic resonance spectroscopy, fully recovered. When ischemic duration was increased from 3 to 12 min, mean recovery time of ATP (6 min) remained rapid but that of pHi (12-28 min) was prolonged. After 30 min of ischemia, pHi recovery was not slowed further (25 min) but that of ATP was now markedly prolonged (36 min). PCr recovery time increased progressively with ischemic duration (5, 11, and 21 min, respectively) and correlated best with SEP recovery (r = 0.74). We conclude that the brain's ability to rapidly normalize pH is a sensitive predictor of electrophysiological recovery after short ischemia but that ATP regeneration becomes important with prolonged ischemia. PCr recovery rate was the best overall predictor, probably because it depends on both pHi and the ratio of ATP to ADP by the creatine kinase reaction.