Phosphocreatine Resynthesis Research Articles

Effect of circulatory occlusion on human muscle metabolism during exercise and recovery

To assess muscle metabolism and inorganic phosphate (P(i)) peak splitting during exercise, 31-phosphorus nuclear magnetic resonance spectroscopy was performed during ramp incremental and submaximal step exercise with and without circulatory occlusion. Seven healthy men performed calf flexion in a superconducting magnet. There was no P(i) splitting during ramp incremental exercise with the circulation present and phosphocreatine (PCr) decreased linearly by 0.07 (SEM 0.01) mmol.l-1.s-1, while exercise with the circulation occluded caused the P(i) peak to split into a high and a low pH peak. The rate of PCr decrease during exercise with the circulation occluded was 0.15 (SEM 0.03) mmol.l-1.s-1 which with the efficiency of the adenosine 5'-triphosphate (ATP) hydrolysis reaction corresponded well to the mechanical energy. Both with and without occlusion of the circulation PCr decreased with some time lag which may reflect the consumption of residual oxygen. In submaximal step exercise PCr decreased exponentially at the onset of exercise with the circulation open whereas it decreased linearly by 0.15 mmol.l-1.s-1 when the circulation was occluded. After exercise, occlusion of the circulation was maintained for 1 min more and there was no PCr resynthesis. It is suggested that ATP synthesis was limited by the availability of oxygen.

Noninvasive measurement of phosphocreatine recovery kinetics in single human muscles.

The rate at which phosphocreatine (PCr) is resynthesized after exercise is related to muscle oxidative capacity (Vmax). With the use of a one-dimensional image-guided, localized nuclear magnetic resonance spectroscopy technique, PCr kinetics were monitored in the medial gastrocnemius of eight healthy subjects after voluntary, short duration, maximal rate exercise. Localized spectra were obtained every 6 s with <5% contamination from nonselected regions. Maximal rate exercise elicited near-maximal to maximal muscle activation, as indicated by the high-PCr hydrolysis rate (2.26 +/- 0.07 mM/s) and extensive PCr depletion. At the end of 9 s of maximal rate exercise, PCr was depleted by 61.4 +/- 2.4% and intracellular pH was 7.04 +/- 0.03. After 9 s of maximal rate exercise, PCr recovered with a rate constant (kPCr) of 1.87 +/- 0.15 min(-1) and a Vmax of 67.2 +/- 6.0 mM/min. Independent of prior activity, aerobic ATP synthesis rates reached 48.6 +/- 4.9 mM/min within 9 s. Extending maximal rate exercise to 30 s resulted in 92.0 +/- 1.2% PCr depletion and an intracellular pH of 6.45 +/- 0.07. The intracellular acidosis separated the direct relationship between kPCr and muscle Vmax but did not affect the initial PCr resynthesis rate.

A model for phosphocreatine resynthesis.

A model for phosphocreatine (PCr) resynthesis is proposed based on a simple electric circuit, where the PCr store in muscle is likened to the stored charge on the capacitor. The solution to the second-order differential equation that describes the potential around the circuit suggests the model for PCr resynthesis is given by PCr(t) = R - [d1.exp(-k1.t) +/- d2.exp(-k2.t)], where R is PCr concentration at rest, d1, d2, k1, and k2 are constants, and t is time. By using nonlinear least squares regression, this double-exponential model was shown to fit the PCr recovery data taken from two studies involving maximal exercise accurately. In study 1, when the muscle was electrically stimulated while occluded, PCr concentrations rose during the recovery phase to a level above that observed at rest. In study 2, after intensive dynamic exercise, PCr recovered monotonically to resting concentrations. The second exponential term in the double-exponential model was found to make a significant additional contribution to the quality of fit in both study 1(P < 0.05) and study 2(P < 0.01).

Skeletal muscle beta-adrenoreceptors and phosphate metabolism abnormalities in heart failure in rats.

To investigate the mechanisms leading to skeletal muscle metabolic abnormalities in chronic heart failure (CHF), we studied phosphate metabolism and skeletal muscle beta-adrenoreceptors (beta-AR) in rats 12-14 wk after coronary ligation (CL). We performed 31P magnetic resonance spectroscopy in the gastrocnemius muscle during motor activity produced by electrical stimulation (5 Hz). The initial slope of phosphocreatine (PCr) depletion was higher in the CL rats compared with sham-operated rats (Pi/PCr/time: 0.211 +/- 0.045 vs. 0.113 +/- 0.029; P < 0.05). During recovery, both PCr resynthesis rate and maximal rate of oxidative ATP synthesis were reduced threefold in the CL rats compared with controls (11 +/- 2 vs. 37 +/- 7 mmol.l-1.min-1, P < 0.04; and 20 +/- 3 vs. 79 +/- 18 mmol.l-1.min-1, P < 0.03, respectively). There were no significant differences either for the skeletal muscle density (13 +/- 6 vs. 15 +/- 3 fM/mg) or for the affinity (0.244 +/- 0.149 vs. 0.246 +/- 0.146 nM) of beta-AR between the two groups. This study showed that, although in moderate CHF skeletal muscle metabolic abnormalities can be demonstrated, these changes could not be explained by skeletal muscle beta-adrenergic receptor alterations in this experimental model.

Magnetic resonance spectroscopy in congenital heart disease.

To determine the feasibility of studying myocardial and skeletal muscle bioenergetics using 31P magnetic resonance spectroscopy (MRS) in babies and young children with congenital heart disease. 16 control subjects aged 5 months to 24 years and 18 patients with CHD, aged 7 months to 23 years, of whom 11 had cyanotic CHD, five had cardiac failure, and two had had a Senning procedure. 31P MRS was carried out using a 1.9 Tesla horizontal 65 cm bore whole body magnet to study the myocardium in 10 patients and skeletal muscle (gastrocnemius) in 14 patients, eight of whom were exercised, together with appropriate controls. In hypoxaemic patients, in skeletal muscle at rest intracellular pH (pHi) was abnormally high [7.06 (SEM 0.04) v 7.04 (0.05), P < 0.01] and showed a positive correlation with haemoglobin (P < 0.03). On exercise, hypoxaemic patients fatigued more quickly but end-exercise pHi and phosphocreatine recovery were normal, implying that an equivalent but smaller amount of work had been performed. End-exercise ADP concentration was lower. On recovery, the initial rate of phosphocreatine resynthesis was low. Skeletal muscle bioenergetics were within normal limits in those in heart failure. In the myocardium, the phosphocreatine/ATP ratio was similar in controls and hypoxaemic subjects, but low in those in heart failure. In heart failure, the myocardial phosphocreatine/ATP ratio was reduced, as in adults, while resting skeletal muscle studies were normal. By contrast, hypoxaemic children had normal myocardial bioenergetics, but showed skeletal muscle alkalinity, and energy reserves were more readily depleted on exercise. On recovery, the initially slow phosphocreatine resynthesis rate reflects a low rate of mitochondrial ATP synthesis, probably due to an inadequate oxygen supply. 31P MRS offers a safe, non-invasive method of studying myocardial and skeletal muscle bioenergetics in children as young as 5 months.

ADP Recovery After a Brief Ischemic Exercise in Normal and Diseased Human Muscle — a31P MRS Study

The pattern of cytosolic ADP recovery after exercise has not been fully characterized in human skeletal muscle. ADP recovery after brief, ischemic exercise was studied by 31phosphorus magnetic resonance spectroscopy in calf muscles of 33 normal control subjects, four patients with McArdle's disease and 13 patients with mitochondrial myopathy. In normal muscle, the half-time for the initial ADP decline was 0.18 +/- 0.07 min and was unaffected by the pH or the metabolic state at the end of exercise. ADP decreased to below rest values during the second min of recovery in 27 out of 33 control subjects. There was a significant (p < 0.001) linear correlation for both the size (r = 0.65) and duration (r = 0.64) of this ADP undershoot with intracellular pH. Phosphocreatine resynthesis continued during the ADP undershoot. ADP undershoot was also found in patients with mitochondrial diseases (in 11 out of 13), but not McArdle's disease (six patients). Thus ADP recovery follows a complex time course that is partly dependent on pH. Only the initial ADP recovery is independent of pH, which makes it suitable for comparative assessment of muscle mitochondrial function in vivo. As phosphocreatine recovery continues during the ADP undershoot, mitochondrial regulation must be different from that at the onset of recovery. These observations are consistent with variable, changing regulators of mitochondrial metabolism in human skeletal muscle.

Reduced oxidative muscle metabolism in chronic fatigue syndrome

The purpose of this study was to determine if chronic fatigue syndrome (CSF) is characterized by abnormalities in oxidative muscle metabolism. Patients with CFS according to Centers for Disease Control (CDC) criteria (n = 22) were compared to normal sedentary subjects (n = 15). CFS patients were also tested before and 2 days after a maximal treadmill test. Muscle oxidative capacity was measured as the maximal rate of postexercise phosphocreatine (PCr) resynthesis using the ADP model (Vmax) in the calf muscles using 31P magnetic resonance spectroscopy. Vmax was significantly reduced in CFS patients (39.6 +/- 2.8 mmol/L/min, mean +/- SE) compared to controls (53.8 +/- 2.8 mmol/L/min). Two days postexercise there was no change in resting inorganic phosphate (Pi)/PCr or Vmax in the CFS patients (n = 14). In conclusion, oxidative metabolism is reduced in CFS patients compared to sedentary controls. In addition, a single bout of strenuous exercise did not cause a further reduction in oxidative metabolism, or alter resting Pi/PCr ratios.

Importance of muscle phosphocreatine during intermittent maximal cycling

To examine the importance of phosphocreatine (PCr) degradation in maintaining power output during maximal intermittent cycling, seven healthy men completed three bouts of isokinetic cycling (30 s, 100 revolutions/min) with 4 min of rest between bouts. After bout 2, blood flow to one leg was occluded by cuffing the thigh (Cuff) during the rest period to prevent PCr resynthesis while the circulation to the other leg was intact (Cont). The cuff was then removed and bout 3 completed. Muscle biopsies were sampled from the vastus lateralis of both legs just before and immediately after bout 3. Total work produced by the Cuff and Cont legs was similar during bouts 1 (9.3 +/- 0.5 and 9.6 +/- 0.5 kJ, respectively) and 2 (8.1 +/- 0.4 and 8.3 +/- kJ, respectively). Cuffing prevented the resynthesis of PCr because pre-bout 3 contents were 20.7 +/- 8.4 and 63.0 +/- 3.3 mmol/kg dry muscle in the Cuff and Cont legs, respectively. Cuffing also resulted in significantly higher muscle levels of lactate, H+ concentration (287 +/- 26 vs. 217 +/- 15 nM), ADP, AMP, and acetyl-CoA before bout 3 but had no effect on other glycolytic intermediates, ATP, or acetylcarnitine. Total work in bout 3 was significantly reduced by 15% in the Cuff leg (5.8 +/- 0.4 vs. 6.8 +/- 0.6 kJ). PCr degradation during bout 3 was 3.1 and 47.5 mmol/kg dry muscle in the Cuff and Cont legs, respectively, and lactate accumulation was minimal in both legs. Changes in all other metabolites during bout 3 were not different between legs. The results suggest that PCr contributed approximately 15% of the total ATP provision during the third 30-s bout of maximal isokinetic cycling and that most of the ATP was provided during the initial 15 s. Muscle glycogenolysis contributed minimally to ATP provision (approximately 10-15%) during the third 30-s bout, suggesting that aerobic metabolism becomes the dominant source of ATP during this model of repeated sprinting.

L-type Ca2+ channel and Na+/Ca2+ exchange inhibitors reduce Ca2+ accumulation in reperfused skeletal muscle.

It is known that extracellular Ca2+ accumulates within skeletal muscle after prolonged periods of ischemia and reperfusion. In this study, we determined whether the L-type Ca2+ channel and the Na+/Ca2+ exchanger mediated Ca2+ influx and whether Ca2+ accumulation limited the metabolic and contractile recovery of reperfused skeletal muscle. Contracting rat hindlimbs (1-Hz twitch) exposed to 40 min of no-flow ischemia were reperfused with diltiazem (500 microM) or 3,4-dichlorobenzamil (300 microM) to block the Na+/Ca2+ exchanger and/or the L-type Ca2+ channel. High inhibitor concentrations were used to counter the binding of diltiazem and 3,4-dichlorobenzamil to albumin and red blood cells. Muscle Ca2+ accumulation, contractile function, and energy metabolism were assessed by measuring intracellular Ca2+ concentration ([Ca2+]i), Ca2+ influx, twitch tension, and high-energy phosphagens [ATP, total adenine nucleotides (TAN) and phosphocreatine (PCr)]. Compared with control reperfusion, diltiazem and 3,4-dichlorobenzamil reduced Ca2+ influx and attenuated the rise in [Ca2+]i in the fast-oxidative glycolytic plantaris (Pl) and the fast-glycolytic white gastrocnemius (WG). The inhibitor-induced decrease in Ca2+ influx was 1.5- to 2-fold greater with 3,4-dichlorobenzamil than with diltiazem. Coinciding with the reduced Ca2+ accumulation, diltiazem and 3,4-dichlorobenzamil enhanced the resynthesis of ATP (Pl and WG), PCr (Pl and WG), and TAN (Pl) compared with control reperfusion. 3,4-Dichlorobenzamil also augmented twitch-tension recovery. We conclude that Ca2+ accumulation during reperfusion 1) arises from L-type Ca2+ channel and Na+/Ca2+ exchange activation; and 2) impairs the metabolic and contractile recovery of skeletal muscle.

Autosomal dominant limb girdle myopathy with ragged-red fibers and cardiomyopathy A pedigree study by in vivo 31P-MR spectroscopy indicating a multisystem mitochondrial defect

We describe a late-onset autosomal dominant limb girdle myopathy, associated with dilated cardiomyopathy and mental deterioration. In two affected members of the pedigree with histochemical (ragged-red and cytocrome c oxidase — negative fibers) and ultrastructural abnormalities of muscle mitochondria, in vivo muscle phosphorus MR spectroscopy disclosed a slow rate of phosphocreatine resynthesis after exercise. Brain phosphorus MR spectroscopy revealed a defect of the energy metabolism in the two patients and in a third asymptomatic member, as shown by a significantly low phosphocreatine, increased ADP and decreased phosphorylation potential. Molecular analysis of muscle mitochondrial DNA failed to reveal any known mutation, including multiple deletions of the mtDNA which have been associated with some autosomal dominant mitochondrial diseases. The multisystem clinical involvement, the presence of ragged-red fibers and the alterations revealed by in vivo brain and muscle 31P-MRS suggest that this limb-girdle syndrome represents an unusual phenotype of mitochondrial cytopathy.

Improvement of muscular oxidative capacity by training is associated with slight acidosis and ATP depletion in exercising muscles.

Metabolic and mechanical properties of female rat skeletal muscles, submitted to endurance training on a treadmill, were studied by a 60-min in vivo multistep fatigue test. 31P-NMR was used to follow energy metabolism and pH. Mechanical performance was greatly improved in trained muscles. The oxidative capacity of the skeletal muscles was evaluated from the relationship between ADP calculated from the creatine kinase equilibrium and work and from the measure of the rate of phosphocreatine (PCr) resynthesis following exercise. In trained muscles, ADP production was lower per unit of mechanical performance, showing an improvement of oxidative metabolism. However, the PCr resynthesis rate was not modified. Slight acidosis and ATP depletion were observed from the beginning of the fatigue test. These modifications suggest changes of the creatine kinase equilibrium favoring mitochondrial ATP production. Our results indicate that muscle status improvement could be accompanied by ATP depletion and minimal acidosis during contraction; this would be of particular importance for objective evaluation of muscle regeneration processes and of gene therapy in muscle diseases.

Improvement of muscular oxidative capacity by training is associated with slight acidosis and ATP depletion in exercising muscles

Metabolic and mechanical properties of female rat skeletal muscles, submitted to endurance training on a treadmill, were studied by a 60-min in vivo multistep fatigue test. 31P-NMR was used to follow energy metabolism and pH. Mechanical performance was greatly improved in trained muscles. The oxidative capacity of the skeletal muscles was evaluated from the relationship between ADP calculated from the creatine kinase equilibrium and work and from the measure of the rate of phosphocreatine (PCr) resynthesis following exercise. In trained muscles, ADP production was lower per unit of mechanical performance, showing an improvement of oxidative metabolism. However, the PCr resynthesis rate was not modified. Slight acidosis and ATP depletion were observed from the beginning of the fatigue test. These modifications suggest changes of the creatine kinase equilibrium favoring mitochondrial ATP production. Our results indicate that muscle status improvement could be accompanied by ATP depletion and minimal acidosis during contraction; this would be of particular importance for objective evaluation of muscle regeneration processes and of gene therapy in muscle diseases. © 1996 John Wiley & Sons, Inc.

Contribution of phosphocreatine and aerobic metabolism to energy supply during repeated sprint exercise.

This study examined the contribution of phosphocreatine (PCr) and aerobic metabolism during repeated bouts of sprint exercise. Eight male subjects performed two cycle ergometer sprints separated by 4 min of recovery during two separate main trials. Sprint 1 lasted 30 s during both main trials, whereas sprint 2 lasted either 10 or 30 s. Muscle biopsies were obtained at rest, immediately after the first 30-s sprint, after 3.8 min of recovery, and after the second 10- and 30-s sprints. At the end of sprint 1, PCr was 16.9 +/- 1.4% of the resting value, and muscle pH dropped to 6.69 +/- 0.02. After 3.8 min of recovery, muscle pH remained unchanged (6.80 +/- 0.03), but PCr was resynthesized to 78.7 +/- 3.3% of the resting value. PCr during sprint 2 was almost completely utilized in the first 10 s and remained unchanged thereafter. High correlations were found between the percentage of PCr resynthesis and the percentage recovery of power output and pedaling speed during the initial 10 s of sprint 2 (r = 0.84, P < 0.05 and r = 0.91, P < 0.01). The anaerobic ATP turnover, as calculated from changes in ATP, PCr, and lactate, was 235 +/- 9 mmol/kg dry muscle during the first sprint but was decreased to 139 +/- 7 mmol/kg dry muscle during the second 30-s sprint, mainly as a result of a approximately 45% decrease in glycolysis. Despite this approximately 41% reduction in anaerobic energy, the total work done during the second 30-s sprint was reduced by only approximately 18%. This mismatch between anaerobic energy release and power output during sprint 2 was partly compensated for by an increased contribution of aerobic metabolism, as calculated from the increase in oxygen uptake during sprint 2 (2.68 +/- 0.10 vs. 3.17 +/- 0.13 l/min; sprint 1 vs. sprint 2; P < 0.01). These data suggest that aerobic metabolism provides a significant part (approximately 49%) of the energy during the second sprint, whereas PCr availability is important for high power output during the initial 10 s.

A multimode dynamometer for in vivo MRS studies of human skeletal muscle.

The implementation of muscle ergometry during magnetic resonance spectroscopy and imaging is complicated by the restrictive dimensions of the magnet bore and the presence of a strong static magnetic field. We have developed a dynamometer that is compatible with these constraints. This device can provide resistance to voluntary muscle contraction during isometric, isokinetic concentric, and isokinetic eccentric muscle contractions. While controlling muscle contraction speed, the dynamometer simultaneously records muscle torque production at a 10-Hz sampling frequency to allow assessment of compliance and retrospective normalization of power output for the mass of active muscle. All parameters relevant to muscle contraction are selectable, including percentage of maximal voluntary contraction, velocity of muscle contraction, duty cycle, and range of motion for the contraction. This paper provides examples of 31P-magnetic resonance spectroscopic measurements during isokinetic concentric contractions of the ankle dorsiflexors, isokinetic eccentric contractions of the soleus, and isometric contractions of the soleus. Operation of the dynamometer has no adverse effects on the integrity of the 31P-magnetic resonance spectra at 4 T, permitting temporal resolution of the phosphocreatine resynthesis rate of approximately 1 spectrum/s. The unique capabilities of this dynamometer will facilitate studies into the metabolic response of working muscle in healthy and diseased populations.

Skeletal muscle mitochondrial dysfunction in alternating hemiplegia of childhood

Alternating hemiplegia of childhood is an uncommon disease characterized by repeated, transient attacks of hemiplegia. Its pathophysiology is uncertain, but attention recently has focused on possible mitochondrial abnormalities. Using 31P magnetic resonance spectroscopy, we studied gastrocnemius muscle in 5 patients with alternating hemiplegia, aged 8 to 30 (mean, 18) years, at rest and during incremental aerobic exercise and recovery. There were no significant differences in resting muscle between patients and a control group aged 7 to 42 (mean, 19) years. Exercise performance was grossly impaired in the patients, the mean duration being 30% of normal. The total change in pH during exercise was somewhat less than in control subjects, while the changes in phosphocreatine concentration and intracellular ADP were similar. Thus the average overall rate of fall of phosphocreatine concentration during exercise was three-fold greater than in control subjects. However, the initial rate of ATP turnover at the start of exercise (a measure of muscle mass and efficiency) was not abnormal. During recovery, both the initial rate of phosphocreatine resynthesis and the calculated mitochondrial capacity were reduced by about 35%. This mitochondrial defect probably explains most of the abnormalities seen during exercise.

The Duration of Infection Modifies Mitochondrial Oxidative Capacity in Rat Skeletal Muscle

Sepsis increases phosphocreatine (PCr) breakdown and reduces PCr stores in skeletal muscle. To determine if systemic infection impairs mitochondrial function, in vivo 13P magnetic resonance spectroscopy ( 31P MRS) studies of the gastrocnemius muscle were performed in virus-free male Wistar rats 24 or 48 hr after cecal ligation and 18-gauge needle single puncture (24°CLP, n = 16; 48°CLP, n = 15) or sham operation (24°SHAM, n = 18; 48°SHAM, n = 13). Physiologic saline (6 ml/100 g body wt) was injected intraperitoneally for fluid resuscitation. Water but no food was allowed in all animals. High resolution (8.45 Tesla) 31P MRS spectra, obtained at rest and during exercise using a 1.4-cm surface coil, were used to calculate PCr/ATP, PCr/ P i ratios, and intracellular pH. Steady-state muscle exercise was induced by supramaximal sciatic nerve stimulation at 10 Hz for 10 min. Recovery of PCr/(PCr + P i) ratios after exercise was fitted to a monoexponential curve. The resultant function was used to calculate the half time for PCr recovery, the initial PCr resynthesis rate, and the maximal oxidative ATP synthesis rate, which reflect the rephosphorylation of ADP and are therefore measures of mitochondrial oxidative capacity. PCr/ATP ratios decreased by 12 and 11%, 24 and 48 hr after CLP, respectively. The PCr/ P i ratios decreased incrementally (7% in 24°CLP vs 23% in 48°CLP animals). Twenty-four hours after operation the half time for PCr recovery was shortened while the initial PCr resynthesis rate and maximal oxidative ATP synthesis rate were accelerated in CLP animals compared to controls. By 48 hr these indices of mitochondrial function were significantly slowed. Intracellular pH was well maintained in resting skeletal muscle in all animals. These data demonstrate that the reduction in high energy phosphate (PCr) stores observed during early sepsis are not secondary to mitochondrial dysfunction; in fact, the organelles' ability to rephosphorylate ADP is enhanced.

Skeletal muscle mitochondrial function studied by kinetic analysis of postexercise phosphocreatine resynthesis.

To investigate mitochondrial regulation and its response to a defect in oxidative metabolism, we used 31P-magnetic resonance spectroscopy to study phosphocreatine (PCr) recovery in rat leg muscle after sciatic nerve stimulation at 1-4 Hz. We studied normal animals and animals with defective skeletal muscle mitochondrial function after experimental cardiac infarction. To analyze these data, we used three current theoretical approaches to the control of mitochondrial ATP synthesis, based on its hyperbolic relationship to cytosolic ADP concentration and on its linear relationships to PCr concentration and the free energy of ATP hydrolysis. The mitochondrial ADP concentration for one-half maximum rate of ATP synthesis appeared at least twice as high as the 30 microM expected from in vitro studies. According to all three approaches, the apparent maximum rate of ATP synthesis was independent of stimulation frequency and end-exercise pH and PCr and ADP concentrations and was reduced by approximately 50% after experimental cardiac infarction. Analysis of PCr recovery kinetics is a robust and practical way to study mitochondrial regulation and to quantify effective mitochondrial defects in vivo.

Creatine and its application as an ergogenic aid.

Phosphocreatine (PCr) availability is likely to limit performance in brief, high-power exercise because the depletion of PCr results in an inability to maintain adenosine triphosphate (ATP) resynthesis at the rate required. It is now known that the daily ingestion of four 5-g doses of creatine for 5 days will significantly increase intramuscular creatine and PCr concentrations prior to exercise and will facilitate PCr resynthesis during recovery from exercise, particularly in those individuals with relatively low creatine concentrations prior to feeding. As a consequence of creatine ingestion, work output during repeated bouts of high-power exercise has been increased under a variety of experimental conditions. The reduced accumulation of ammonia and hypoxanthine in plasma and the attenuation of muscle ATP degradation after creatine feeding suggest that the ergogenic effect of creatine is achieved by better maintaining ATP turnover during contraction.

Recovery of power output and muscle metabolites following 30 s of maximal sprint cycling in man.

1. The recovery of power output and muscle metabolites was examined following maximal sprint cycling exercise. Fourteen male subjects performed two 30 s cycle ergometer sprints separated by 1.5, 3 and 6 min of recovery, on three separate occasions. On a fourth occasion eight of the subjects performed only one 30 s sprint and muscle biopsies were obtained during recovery. 2. At the end of the 30 s sprint phosphocreatine (PCr) and ATP contents were 19.7 +/- 1.2 and 70.5 +/- 6.5% of the resting values (rest), respectively, while muscle lactate was 119.0 +/- 4.6 mmol (kg dry wt)-1 and muscle pH was 6.72 +/- 0.06. During recovery, PCr increased rapidly to 65.0 +/- 2.8% of rest after 1.5 min, but reached only 85.5 +/- 3.5% of rest after 6 min of recovery. At the same time ATP and muscle pH remained low (19.5 +/- 0.9 mmol (kg dry wt)-1 and 6.79 +/- 0.02, respectively). Modelling of the individual PCr resynthesis using a power function curve gave an average half-time for PCr resynthesis of 56.6 +/- 7.3 s. 3. Recovery of peak power output (PPO), peak pedal speed (maxSp) and mean power during the initial 6 s (MPO6) of sprint 2 did not reach the control values after 6 min of rest, and occurred in parallel with the resynthesis of PCr, despite the low muscle pH. High correlations (r = 0.71-0.86; P < 0.05) were found between the percentage resynthesis of PCr and the percentage restoration of PPO, maxSp and MPO6 after 1.5 and 3 min of recovery. No relationship was observed between muscle pH recovery and power output restoration during sprint 2 (P > 0.05). 4. These data suggest that PCr resynthesis after 30 s of maximal sprint exercise is slower than previously observed after dynamic exercise of longer duration, and PCr resynthesis is important for the recovery of power during repeated bouts of sprint exercise.

Control of the rate of phosphocreatine resynthesis after exercise in trained and untrained human quadriceps muscles.

We examined the effect of differences in exercise intensity on the time constant (tc) of phosphocreatine (PCr) resynthesis after exercise and the relationships between tc and maximal oxygen uptake (VO2max) in endurance-trained runners (n = 5) and untrained controls (n = 7) (average VO2max = 66.2 and 52.0 ml.min-1.kg-1, respectively). To measure the metabolism of the quadriceps muscle using phosphorus nuclear magnetic resonance spectroscopy, we developed a device which allowed knee extension exercise inside a magnet. All the subjects performed four types of exercise: light, moderate, severe and exhausting. The end-exercise PCr: [PCr+inorganic phosphate (P(i))] ratio decreased significantly with the increase in the exercise intensity (P < 0.01). Although there was little difference in the end-exercise pH, adenosine diphosphate concentration ([ADP]) and the lowest intracellular pH during recovery between light and moderate exercise, significant changes were found at the two higher intensities (P < 0.01). These changes for runners were smaller than those for the controls (P < 0.05). The tc remained constant after light and moderate exercise and then lengthened in proportion to the increase in intensity (P < 0.05). The runners had a lower tc at the same PCr and pH than the controls, particularly at the higher intensity (P < 0.05). There was a significant correlation between tc and [ADP] in light exercise and between tc and both end-exercise PCr and pH in severe and exhausting exercise (P < 0.05). The threshold of changes in pH and tc was a PCr: (PCr+P(i)) ratio of 0.5. There was a significant negative correlation between the VO2max and tc after all levels of exercise (P < 0.05). However, in the controls a significant correlation was found in only light and moderate exercise (P < 0.05). These findings suggest the validity of the use of tc at an end-exercise PCr: (PCr+P(i)) ratio of more than 0.5 as a stable index of muscle oxidative capacity and the correlation between local and general aerobic capacity. Moreover, endurance-trained runners are characterized by the faster PCr resynthesis at the same PCr and intracellular pH.