Metabolic effects of induced alkalosis during progressive forearm exercise to fatigue.

Metabolic alkalosis induced by sodium bicarbonate (NaHCO(3)) ingestion has been shown to enhance performance during brief high-intensity exercise. The mechanisms associated with this increase in performance may include increased muscle phosphocreatine (PCr) breakdown, muscle glycogen utilization, and plasma lactate (Lac(-)(pl)) accumulation. Together, these changes would imply a shift toward a greater contribution of anaerobic energy production, but this statement has been subject to debate. In the present study, subjects (n = 6) performed a progressive wrist flexion exercise to volitional fatigue (0.5 Hz, 14-21 min) in a control condition (Con) and after an oral dose of NaHCO(3) (Alk: 0.3 g/kg; 1.5 h before testing) to evaluate muscle metabolism over a complete range of exercise intensities. Phosphorus-31 magnetic resonance spectroscopy was used to continuously monitor intracellular pH, [PCr], [P(i)], and [ATP] (brackets denote concentration). Blood samples drawn from a deep arm vein were analyzed with a blood gas-electrolyte analyzer to measure plasma pH, Pco(2), and [Lac(-)](pl), and plasma [HCO(3)(-)] was calculated from pH and Pco(2). NaHCO(3) ingestion resulted in an increased (P < 0.05) plasma pH and [HCO(3)(-)] throughout rest and exercise. Time to fatigue and peak power output were increased (P < 0.05) by approximately 12% in Alk. During exercise, a delayed (P < 0.05) onset of intracellular acidosis (1.17 +/- 0.26 vs. 1.28 +/- 0.22 W, Con vs. Alk) and a delayed (P < 0.05) onset of rapid increases in the [P(i)]-to-[PCr] ratio (1.21 +/- 0.30 vs. 1.30 +/- 0.30 W) were observed in Alk. No differences in total [H(+)], [P(i)], or [Lac(-)](pl) accumulation were detected. In conclusion, NaHCO(3) ingestion was shown to increase plasma pH at rest, which resulted in a delayed onset of intracellular acidification during incremental exercise. Conversely, NaHCO(3) was not associated with increased [Lac(-)](pl) accumulation or PCr breakdown.     

Muscle metabolic status and acid-base balance during 10-s work:5-s recovery intermittent and continuous exercise

Gastrocnemius muscle phosphocreatine ([PCr]) and hydrogen ion ([H(+)]) were measured using (31)P-magnetic resonance spectroscopy during repeated bouts of 10-s heavy-intensity (HI) exercise and 5-s rest compared with continuous (CONT) HI exercise. Recreationally active male subjects (n = 7; 28 yr ± 9 yr) performed on separate occasions 12 min of isotonic plantar flexion (0.75 Hz) CONT and intermittent (INT; 10-s exercise, 5-s rest) exercise. The HI power output in both CONT and INT was set at 50% of the difference between the power output associated with the onset of intracellular acidosis and peak exercise determined from a prior incremental plantar flexion protocol. Intracellular concentrations of [PCr] and [H(+)] were calculated at 4 s and 9 s of the work period and at 4 s of the rest period in INT and during CONT exercise. [PCr] and [H(+)] (mean ± SE) were greater at 4 s of the rest periods vs. 9 s of exercise over the course of the INT exercise bout: [PCr] (20.7 mM ± 0.6 vs. 18.7 mM ± 0.5; P < 0.01); [H(+)] (370 nM ± 13.50 vs. 284 nM ± 13.6; P < 0.05). Average [H(+)] was similar for CONT vs. INT. We therefore suggest that there is a glycolytic contribution to ATP recovery during the very short rest period (<5 s) of INT and that the greater average power output of CONT did not manifest in greater [H(+)] and greater glycolytic contribution compared with INT exercise.     

Prior exercise delays the onset of acidosis during incremental exercise.

The effects of prior moderate- and prior heavy-intensity exercise on the subsequent metabolic response to incremental exercise were examined. Healthy, young adult subjects (n = 8) performed three randomized plantar-flexion exercise tests: 1) an incremental exercise test (approximately 0.6 W/min) to volitional fatigue (Ramp); 2) Ramp preceded by 6 min of moderate-intensity, constant-load exercise below the intracellular pH threshold (pHT; Mod-Ramp); and 3) Ramp preceded by 6 min of heavy-intensity, constant-load exercise above pHT (Hvy-Ramp); the constant-load and incremental exercise periods were separated by 6 min of rest. (31)P-magnetic resonance spectroscopy was used to continuously monitor intracellular pH, phosphocreatine concentration ([PCr]), and inorganic phosphate concentration ([P(i)]). No differences in exercise performance or the metabolic response to exercise were observed between Ramp and Mod-Ramp. However, compared with Ramp, a 14% (SD 10) increase (P < 0.01) in peak power output (PPO) was observed in Hvy-Ramp. The improved exercise performance in Hvy-Ramp was accompanied by a delayed (P = 0.01) onset of intracellular acidosis [Hvy-Ramp 60.4% PPO (SD 11.7) vs. Ramp 45.8% PPO (SD 9.4)] and a delayed (P < 0.01) onset of rapid increases in [P(i)]/[PCr] [Hvy-Ramp 61.5% PPO (SD 12.0) vs. Ramp 45.1% PPO (SD 9.1)]. In conclusion, prior heavy-intensity exercise delayed the onset of intracellular acidosis and enhanced exercise performance during a subsequent incremental exercise test.     

31P magnetic resonance spectroscopy study of phosphocreatine recovery kinetics in skeletal muscle: the issue of intersubject variability

We have analyzed by (31)P MRS the relationship between kinetic parameters of phosphocreatine (PCr) recovery and end-of-exercise status under conditions of moderate and large acidosis induced by dynamic exercise. Thirteen healthy subjects performed muscular contractions at 0.47 Hz (low frequency, moderate exercise) and 0.85 Hz (high frequency, heavy exercise). The rate constant of PCr resynthesis (k(PCr)) varied greatly among subjects (variation coefficients: 43 vs. 57% for LF vs. HF exercises) and protocols (k(PCr) values: 1.3+/-0.5 min(-1) vs. 0.9+/-0.5 min(-1) for LF vs. HF exercises, P<0.03). The large intersubject variability can be captured into a linear relationship between k(PCr), the amount of PCr consumed ([PCr(2)]) and pH reached at the end of exercise (pH(end)) (k(PCr)=-3.3+0.7 pH(end)-0.03 [PCr(2)]; P=0.0007; r=0.61). This dual relationship illustrates that mitochondrial activity is affected by end-of-exercise metabolic status and allows reliable comparisons between control, diseased and trained muscles. In contrast to k(PCr), the initial rate of PCr recovery and the maximum oxidative capacity were always constant whatever the metabolic conditions of end-of-exercise and can then be additionally used in the identification of dysfunctions in the oxidative metabolic pathway.     

NaHCO3-induced alkalosis reduces the phosphocreatine slow component during heavy-intensity forearm exercise.

During heavy-intensity exercise, the mechanisms responsible for the continued slow decline in phosphocreatine concentration ([PCr]) (PCr slow component) have not been established. In this study, we tested the hypothesis that a reduced intracellular acidosis would result in a greater oxidative flux and, consequently, a reduced magnitude of the PCr slow component. Subjects (n = 10) performed isotonic wrist flexion in a control trial and in an induced alkalosis (Alk) trial (0.3g/kg oral dose of NaHCO3, 90 min before testing). Wrist flexion, at a contraction rate of 0.5 Hz, was performed for 9 min at moderate- (75% of onset of acidosis; intracellular pH threshold) and heavy-intensity (125% intracellular pH threshold) exercise. 31P-magnetic resonance spectroscopy was used to measure intracellular [H+], [PCr], [Pi], and [ATP]. The initial recovery data were used to estimate the rate of ATP synthesis and oxidative flux at the end of heavy-intensity exercise. In repeated trials, venous blood sampling was used to measure plasma [H+], [HCO3-], and [Lac-]. Throughout rest and exercise, plasma [H+] was lower (P < 0.05) and [HCO3-] was elevated (P < 0.05) in Alk compared with control. During the final 3 min of heavy-intensity exercise, Alk caused a lower (P < 0.05) intracellular [H+] [246 (SD 117) vs. 291 nmol/l (SD 129)], a greater (P < 0.05) [PCr] [12.7 (SD 7.0) vs. 9.9 mmol/l (SD 6.0)], and a reduced accumulation of [ADP] [0.065 (SD 0.031) vs. 0.098 mmol/l (SD 0.059)]. Oxidative flux was similar (P > 0.05) in the conditions at the end of heavy-intensity exercise. In conclusion, our results are consistent with a reduced intracellular acidosis, causing a decrease in the magnitude of the PCr slow component. The decreased PCr slow component in Alk did not appear to be due to an elevated oxidative flux.     

Human muscle fatigue after glycogen depletion: a 31P magnetic resonance study.

To differentiate the effects of high energy phosphates, pH, and [H2PO4-] on skeletal muscle fatigue, intracellular acidosis during handgrip exercise was attenuated by prolonged submaximal exercise. Healthy human subjects (n = 6) performed 5-min bouts of maximal rhythmic handgrip (RHG) before (CONTROL) and after prolonged (60-min) handgrip exercise (ATTEN-EX) designed to attenuate lactic acidosis in active muscle by partially depleting muscle glycogen. Concentrations of free intracellular phosphocreatine ([PCr]), adenosine triphosphate ([ATP]), and orthophosphate ([P(i)]) and pH were measured by 31P nuclear magnetic resonance spectroscopy and used to calculate adenosine diphosphate [ADP], [H2PO4-], and [HPO4(2-)]. Handgrip force output was measured with a dynamometer, and fatigue was determined by loss of maximal contractile force. After ATTEN-EX, the normal exercise-induced muscle acidosis was reduced. At peak CONTROL RHG, pH fell to 6.3 +/- 0.1 (SE) and muscle fatigue was correlated with [PCr] (r = 0.83), [P(i)] (r = 0.82), and [H2PO4-] (r = 0.81); [ADP] was 22.0 +/- 5.7 mumol/kg. At peak RHG after ATTEN-EX, pH was 6.9 +/- 0.1 and [ADP] was 116.1 +/- 18.2 mumol/kg, although [PCr] and [P(i)] were not different from CONTROL RHG (P greater than 0.05). After ATTEN-EX, fatigue correlated most closely with [ADP] (r = 0.84). The data indicate that skeletal muscle fatigue 1) is multifactorial, 2) can occur without decreased pH or increased [H2PO4-], and 3) is correlated with [ADP] after exercise-induced glycogen depletion.     

Combined in situ analysis of metabolic and myoelectrical changes associated with electrically induced fatigue.

Electrical muscle stimulation (Mstim) at a low or high frequency is associated with failure of force production, but the exact mechanisms leading to fatigue in this model are still poorly understood. Using 31P magnetic resonance spectroscopy (31PMRS), we investigated the metabolic changes in rabbit tibialis anterior muscle associated with the force decline during Mstim at low (10 Hz) and high (100 Hz) frequency. We also simultaneously recorded the compound muscle mass action potential (M-wave) evoked by direct muscle stimulation, and we analyzed its post-Mstim variations. The 100-Hz Mstim elicited marked M-wave alterations and induced mild metabolic changes at the onset of stimulation followed by a paradoxical recovery of phosphocreatine (PCr) and pH during the stimulation period. On the contrary, the 10-Hz Mstim produced significant PCr consumption and intracellular acidosis with no paradoxical recovery phenomenon and no significant changes in M-wave characteristics. In addition, the force depression was linearly linked to the stimulation-induced acidosis and PCr breakdown. These results led us to conclude that force failure during 100-Hz Mstim only results from an impaired propagation of muscle action potentials with no metabolic involvement. On the contrary, fatigue induced by 10-Hz Mstim is closely associated with metabolic changes with no alteration of the membrane excitability, thereby underlining the central role of muscle energetics in force depression when muscle is stimulated at low frequency. Finally, our results further indicate a reduction of energy cost of contraction when stimulation frequency is increased from 10 to 100 Hz.     

Muscle oxidative metabolism accelerates with mild acidosis during incremental intermittent isometric plantar flexion exercise

BACKGROUND: It has been thought that intramuscular ADP and phosphocreatine (PCr) concentrations are important regulators of mitochondorial respiration. There is a threshold work rate or metabolic rate for cellular acidosis, and the decrease in muscle PCr is accelerated with drop in pH during incremental exercise. We tested the hypothesis that increase in muscle oxygen consumption (o2mus) is accelerated with rapid decrease in PCr (concomitant increase in ADP) in muscles with drop in pH occurs during incremental plantar flexion exercise. METHODS: Five male subjects performed a repetitive intermittent isometric plantar flexion exercise (6-s contraction/4-s relaxation). Exercise intensity was raised every 1 min by 10% maximal voluntary contraction (MVC), starting at 10% MVC until exhaustion. The measurement site was at the medial head of the gastrocnemius muscle. Changes in muscle PCr, inorganic phosphate (Pi), ADP, and pH were measured by 31P-magnetic resonance spectroscopy. o2mus was determined from the rate of decrease in oxygenated hemoglobin and/or myoglobin using near-infrared continuous wave spectroscopy under transient arterial occlusion. Electromyogram (EMG) was also recorded. Pulmonary oxygen uptake (o2pul ) was measured by the breath-by-breath gas analysis. RESULTS: EMG amplitude increased as exercise intensity progressed. In contrast, muscle PCr, ADP, o2mus, and o2pul did not change appreciably below 40% MVC, whereas above 40% MVC muscle PCr decreased, and ADP, o2mus, and o2pul increased as exercise intensity progressed, and above 70% MVC, changes in muscle PCr, ADP, o2mus, and o2pul accelerated with the decrease in muscle pH (~6.78). The kinetics of muscle PCr, ADP, o2mus, and o2pul were similar, and there was a close correlation between each pair of parameters (r = 0.969~0.983, p < 0.001). CONCLUSION: With decrease in pH muscle oxidative metabolism accelerated and changes in intramuscular PCr and ADP accelerated during incremental intermittent isometric plantar flexion exercise. These results suggest that rapid changes in muscle PCr and/or ADP with mild acidosis stimulate accelerative muscle oxidative metabolism.     

Muscle metabolic responses to exercise above and below the "critical power" assessed using 31P-MRS

We tested the hypothesis that the asymptote of the hyperbolic relationship between work rate and time to exhaustion during muscular exercise, the "critical power" (CP), represents the highest constant work rate that can be sustained without a progressive loss of homeostasis [as assessed using (31)P magnetic resonance spectroscopy (MRS) measurements of muscle metabolites]. Six healthy male subjects initially completed single-leg knee-extension exercise at three to four different constant work rates to the limit of tolerance (range 3-18 min) for estimation of the CP (mean +/- SD, 20 +/- 2 W). Subsequently, the subjects exercised at work rates 10% below CP (CP) for as long as possible, while the metabolic responses in the contracting quadriceps muscle, i.e., phosphorylcreatine concentration ([PCr]), P(i) concentration ([P(i)]), and pH, were estimated using (31)P-MRS. All subjects completed 20 min of CP exercise was 14.7 +/- 7.1 min. During CP exercise, however, [PCr] continued to fall to the point of exhaustion and [P(i)] and pH changed precipitously to values that are typically observed at the termination of high-intensity exhaustive exercise (end-exercise values = 26 +/- 16% of baseline [PCr], 564 +/- 167% of baseline [P(i)], and pH 6.87 +/- 0.10, all P < 0.05 vs. 相似文献   

Muscle acidosis during static exercise is associated with calf vasoconstriction

In this study we measured (n = 6) the phosphocreatine-to-inorganic phosphate ratio (PCr/Pi), Pi, and pH with 31P-nuclear magnetic resonance (31P-NMR) in the human forearm during static work at 30% of maximal voluntary contraction (MVC) for 2 min followed immediately by 3 min of circulatory arrest (forearm arterial occlusion). Static exercise, with its central volitional and skeletal muscle metabolic and mechanical afferent components, caused a rise in heart rate (HR, 32%), blood pressure (BP, 29%), and calf vascular resistance (calf R, 30%). During forearm occlusion after static exercise, HR returned to base line, the increase in BP was attenuated by 30%, and calf R remained elevated and unchanged. The percent change in calf R was correlated with forearm cellular pH (R = 0.56, P less than 0.001) but only weakly associated with PCr/Pi (R = 0.33, P less than 0.042). 30% MVC for 1 min followed by arterial occlusion (3 min) reduced PCr/Pi by 65% and pH by 0.16 U (P less than 0.05). Calf R was unchanged. Circulatory arrest alone (20 min) caused no change in either pH or calf R but large changes in PCr/Pi (50% reduction). We conclude that 1) there is an association between forearm cellular acidosis and calf vasconstriction during static forearm exercise and 2) large changes in PCr/Pi without concomitant changes in pH are not associated with changes in calf R.     

Human muscle performance and PCr hydrolysis with varied inspired oxygen fractions: a 31P-MRS study.

The purpose of this study was to use 31P-magnetic resonance spectroscopy to examine the relationships among muscle PCr hydrolysis, intracellular H+ concentration accumulation, and muscle performance during incremental exercise during the inspiration of gas mixtures containing different fractions of inspired O2 (FIO2). We hypothesized that lower FIO2 would result in a greater disruption of intracellular homeostasis at submaximal workloads and thereby initiate an earlier onset of fatigue. Six subjects performed plantar flexion exercise on three separate occasions with the only variable altered for each exercise bout being the FIO2 (either 0.1, 0.21, or 1.00 O2 in balance N2). Work rate was increased (1-W increments starting at 0 W) every 2 min until exhaustion. Time to exhaustion (and thereby workload achieved) was significantly (P < 0.05) greater as FIO2 was increased. Muscle phosphocreatine (PCr) concentration, Pi concentration, and pH at exhaustion were not significantly different among the three FIO2 conditions. However, muscle PCr concentration and pH were significantly reduced at identical submaximal workloads (and thereby equivalent rates of respiration) above 4-5 W during the lowest FIO2 condition compared with the other two FIO2 conditions. These results demonstrate that exhaustion during all FIO2 occurred when a particular intracellular environment was achieved and suggest that during the lowest FIO2 condition, the greater PCr hydrolysis and intracellular acidosis at submaximal workloads may have contributed to the significantly earlier time to exhaustion.     

Influence of endurance training on muscle [PCr] kinetics during high-intensity exercise

We hypothesized that a period of endurance training would result in a speeding of muscle phosphocreatine concentration ([PCr]) kinetics over the fundamental phase of the response and a reduction in the amplitude of the [PCr] slow component during high-intensity exercise. Six male subjects (age 26 +/- 5 yr) completed 5 wk of single-legged knee-extension exercise training with the alternate leg serving as a control. Before and after the intervention period, the subjects completed incremental and high-intensity step exercise tests of 6-min duration with both legs separately inside the bore of a whole-body magnetic resonance spectrometer. The time-to-exhaustion during incremental exercise was not changed in the control leg [preintervention group (PRE): 19.4 +/- 2.3 min vs. postintervention group (POST): 19.4 +/- 1.9 min] but was significantly increased in the trained leg (PRE: 19.6 +/- 1.6 min vs. POST: 22.0 +/- 2.2 min; P < 0.05). During step exercise, there were no significant changes in the control leg, but end-exercise pH and [PCr] were higher after vs. before training. The time constant for the [PCr] kinetics over the fundamental exponential region of the response was not significantly altered in either the control leg (PRE: 40 +/- 13 s vs. POST: 43 +/- 10 s) or the trained leg (PRE: 38 +/- 8 s vs. POST: 40 +/- 12 s). However, the amplitude of the [PCr] slow component was significantly reduced in the trained leg (PRE: 15 +/- 7 vs. POST: 7 +/- 7% change in [PCr]; P < 0.05) with there being no change in the control leg (PRE: 13 +/- 8 vs. POST: 12 +/- 10% change in [PCr]). The attenuation of the [PCr] slow component might be mechanistically linked with enhanced exercise tolerance following endurance training.     

31-P NMR characterization of the metabolic anomalies associated with the lack of glycogen phosphorylase activity in human forearm muscle.

Exercise-induced changes in phosphorus-containing metabolites and intracellular pH (pHi) have been studied in the finger flexor muscles of 3 patients with glycogen phosphorylase deficiency (McArdle's disease) in comparison to 14 healthy volunteers. At rest, no difference was observed for PCr/Pi ratio and pHi while patients exhibited a higher PCr/ATP ratio (5.91 +/- 0.98 vs 4.02 +/- 0.6). At end-of-exercise, PCr/Pi was abnormally low (0.51 +/- 0.19 vs 1.64 +/- 0.37) whereas no acidosis was observed. The slow recovery of PCr/Pi ratio indicates an impairment of oxidative capacity accompanying the defect in the glycogenolytic pathway. The failure to observe a transient Pi disappearance at the onset of recovery (an index of glycogen phosphorylase activity) can be used in conjunction with the lack of exercise acidosis as a diagnostic index of McArdle's disease.     

Changes in tissue water content measured with multiple-frequency bioimpedance and metabolism measured with 31P-MRS during progressive forearm exercise.

Multiple-frequency bioimpedance analysis (MFBIA) has been used to determine the cellular water composition in the human body. It is noninvasive and has demonstrated good correlations with other invasive measures of tissue water. However, the ability of this method to study transient changes in tissue water in specific muscle groups has not been explored. In this study, MFBIA was used to assess changes in forearm intracellular water (ICW), extracellular water (ECW), and total water (TW) in seven healthy volunteers during and after a progressive wrist flexion exercise protocol. In an identical trial, (31)P magnetic resonance spectroscopy ((31)P-MRS) was used to assess changes in intracellular pH and phosphocreatine (PCr). At the completion of exercise, forearm ICW increased 12.6% (SD 0.07, P = 0.003), TW increased 10.1% (SD 0.06, P = 0.005), and no significant changes were recorded for ECW. A significant correlation was found between the changes in intracellular pH and changes in ICW during exercise (r = -0.84, P = 0.018). With the use of regression analysis, average changes in P(i), PCr, and pH were found to predict changes in ICW (R(2) = 0.98, P = 0.005). In conclusion, MFBIA was sensitive enough to measure transient changes in the exercising forearm muscle. The changes seen were consistent with the hypothesis that intracellular acidification and PCr hydrolysis are important mediators of cellular osmolality and therefore may be responsible for the increased volume of water in the intracellular space that is often recorded after short-term high-intensity exercise.     

Metabolic determinants of the onset of acidosis in exercising human muscle: a 31P-MRS study.

Onset of intracellular acidosis during muscular exercise has been generally attributed to activation or hyperactivation of nonoxidative ATP production but has not been analyzed quantitatively in terms of H(+) balance, i.e., production and removal mechanisms. To address this issue, we have analyzed the relation of intracellular acidosis to H(+) balance during exercise bouts in seven healthy subjects. Each subject performed a 6-min ramp rhythmic exercise (finger flexions) at low frequency (LF, 0.47 Hz), leading to slight acidosis, and at high frequency (HF, 0.85 Hz), inducing a larger acidosis. Metabolic changes were recorded using (31)P-magnetic resonance spectroscopy. Onset of intracellular acidosis was statistically identified after 3 and 4 min of exercise for HF and LF protocols, respectively. A detailed investigation of H(+) balance indicated that, for both protocols, nonoxidative ATP production preceded a change in pH. For HF and LF protocols, H(+) consumption through the creatine kinase equilibrium was constant in the face of increasing H(+) generation and efflux. For both protocols, changes in pH were not recorded as long as sources and sinks for H(+) approximately balanced. In contrast, a significant acidosis occurred after 4 min of LF exercise and 3 min of HF exercise, whereas the rise in H(+) generation exceeded the rise in H(+) efflux at a nearly constant H(+) uptake associated with phosphocreatine breakdown. We have clearly demonstrated that intracellular acidosis in exercising muscle does not occur exclusively as a result of nonoxidative ATP production but, rather, reflects changes in overall H(+) balance.     

Effects of hyperventilation on phosphocreatine kinetics and muscle deoxygenation during moderate-intensity plantar flexion exercise.

The effects of controlled voluntary hyperventilation (Hyp) on phosphocreatine (PCr) kinetics and muscle deoxygenation were examined during moderate-intensity plantar flexion exercise. Male subjects (n = 7) performed trials consisting of 20-min rest, 6-min exercise, and 10-min recovery in control [Con; end-tidal Pco(2) (Pet(CO(2))) approximately 33 mmHg] and Hyp (Pet(CO(2)) approximately 17 mmHg) conditions. Phosphorus-31 magnetic resonance and near-infrared spectroscopy were used simultaneously to monitor intramuscular acid-base status, high-energy phosphates, and muscle oxygenation. Resting intracellular hydrogen ion concentration ([H(+)](i)) was lower (P < 0.05) in Hyp [90 nM (SD 3)] than Con [96 nM (SD 4)]; however, at end exercise, [H(+)](i) was greater (P < 0.05) in Hyp [128 nM (SD 19)] than Con [120 nM (SD 17)]. At rest, [PCr] was not different between Con [36 mM (SD 2)] and Hyp [36 mM (SD 1)]. The time constant (tau) of PCr breakdown during transition from rest to exercise was greater (P < 0.05) in Hyp [39 s (SD 22)] than Con [32 s (SD 22)], and the PCr amplitude was greater (P < 0.05) in Hyp [26% (SD 4)] than Con [22% (SD 6)]. The deoxyhemoglobin and/or deoxymyoglobin (HHb) tau was similar between Hyp [13 s (SD 8)] and Con [10 s (SD 3)]; however, the amplitude was increased (P < 0.05) in Hyp [40 arbitrary units (au) (SD 23)] compared with Con [26 au (SD 17)]. In conclusion, our results indicate that Hyp-induced hypocapnia enhanced substrate-level phosphorylation during moderate-intensity exercise. In addition, the increased amplitude of the HHb response suggests a reduced local muscle perfusion in Hyp compared with Con.     

Neural and metabolic mechanisms of excessive muscle fatigue in maintenance hemodialysis patients

Dialysis patients have severe exercise limitations related to metabolic disturbances, but muscle fatigue has not been well studied in this population. We investigated the magnitude and mechanisms of fatigue of the ankle dorsiflexor muscles in patients on maintenance hemodialysis. Thirty-three dialysis patients and twelve healthy control subjects performed incremental isometric dorsiflexion exercise, beginning at 10% of their maximal voluntary contraction (MVC) and increasing by 10% every 2 min. Muscle fatigue (fall of MVC), completeness of voluntary activation, and metabolic responses to exercise were measured. Before exercise, dialysis subjects exhibited reduced strength and impaired peripheral activation (lower compound muscle activation potential amplitude) but no metabolic perturbation. During exercise, dialysis subjects demonstrated threefold greater fatigue than controls with evidence of central activation failure but no change in peripheral activation. All metabolic parameters were significantly more perturbed at end exercise in dialysis subjects than in controls, including lower phosphocreatine (PCr) and pH, and higher P(i), P(i)/PCr, and H(2)PO(4)(-). Oxidative potential was markedly lower in patients than in controls [62.5 (SD 27.2) vs. 134.6 (SD 31.7), P < 0.0001]. Muscle fatigue was negatively correlated with oxidative potential among dialysis subjects (r = -0.52, P = 0.04) but not controls. Changes in central activation ratio were also correlated with muscle fatigue in the dialysis subjects (r = 0.59, P = 0.001) but not the controls. This study provides new information regarding the excessive muscular fatigue of dialysis patients and demonstrates that the mechanisms of this fatigue include both intramuscular energy metabolism and central activation failure.     

Energy metabolism during repeated sets of leg press exercise leading to failure or not

This investigation examined the influence of the number of repetitions per set on power output and muscle metabolism during leg press exercise. Six trained men (age 34 ± 6 yr) randomly performed either 5 sets of 10 repetitions (10REP), or 10 sets of 5 repetitions (5REP) of bilateral leg press exercise, with the same initial load and rest intervals between sets. Muscle biopsies (vastus lateralis) were taken before the first set, and after the first and the final sets. Compared with 5REP, 10REP resulted in a markedly greater decrease (P<0.05) of the power output, muscle PCr and ATP content, and markedly higher (P<0.05) levels of muscle lactate and IMP. Significant correlations (P<0.01) were observed between changes in muscle PCr and muscle lactate (R(2) = 0.46), between changes in muscle PCr and IMP (R(2) = 0.44) as well as between changes in power output and changes in muscle ATP (R(2) = 0.59) and lactate (R(2) = 0.64) levels. Reducing the number of repetitions per set by 50% causes a lower disruption to the energy balance in the muscle. The correlations suggest that the changes in PCr and muscle lactate mainly occur simultaneously during exercise, whereas IMP only accumulates when PCr levels are low. The decrease in ATP stores may contribute to fatigue.     

Kinetics of anaerobic metabolism in human skeletal muscle: influence of repetitive high-intensity exercise on sedentary dominant and non-dominant forearm. A 31P NMR study

Potential differences were assessed between the dominant (D) and non-dominant (ND) forearms of sedentary subjects during anaerobic exercise. Subjects performed voluntary concentric contractions of D and ND forearm muscle during a series of three high-intensity (60% of the maximal voluntary contraction force (MVC)) exercise bouts. The time-dependent changes in intracellular pH (pH(i)), Pi, and PCr concentrations, and their relation to muscular work were examined using 31P magnetic resonance spectroscopy (MRS) techniques, and revealed that D forearm metabolic kinetics in sedentary individuals are improved during repetitive high-intensity exercise compared to their respective ND forearm muscle. We postulate that the more regular and preferential utilization of the D limb leads to a "trained-like" condition.     

The effect of higher ATP cost of contraction on the metabolic response to graded exercise in patients with chronic obstructive pulmonary disease

To better understand the metabolic implications of a higher ATP cost of contraction in chronic obstructive pulmonary disease (COPD), we used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to examine muscle energetics and pH in response to graded exercise. Specifically, in six patients and six well-matched healthy controls, we determined the intracellular threshold for pH (T(pH)) and inorganic phosphate-to-phosphocreatine ratio (T(Pi/PCr)) during progressive dynamic plantar flexion exercise with work rate expressed as both absolute and relative intensity. Patients with COPD displayed a lower peak power output (WRmax) compared with controls (controls 25 ± 4 W, COPD 15 ± 5 W, P = 0.01) while end-exercise pH (controls 6.79 ± 0.15, COPD 6.76 ± 0.21, P = 0.87) and PCr consumption (controls 82 ± 10%, COPD 70 ± 18%, P = 0.26) were similar between groups. Both T(pH) and T(Pi/PCr) occurred at a significantly lower absolute work rate in patients with COPD compared with controls (controls: 14.7 ± 2.4 W for T(pH) and 15.3 ± 2.4 W for T(Pi/PCr); COPD: 9.7 ± 4.5 W for T(pH) and 10.0 ± 4.6 W for T(Pi/PCr), P < 0.05), but these thresholds occurred at the same percentage of WRmax (controls: 63 ± 11% WRmax for T(pH) and 67 ± 18% WRmax for T(Pi/PCr); COPD: 59 ± 9% WRmax for T(pH) and 61 ± 12% WRmax for T(Pi/PCr), P > 0.05). Indexes of mitochondrial function, the PCr recovery time constant (controls 42 ± 7 s, COPD 45 ± 11 s, P = 0.66) and the PCr resynthesis rate (controls 105 ± 21%/min, COPD 91 ± 31%/min, P = 0.43) were similar between groups. In combination, these results reveal that when energy demand is normalized to WRmax, as a consequence of higher ATP cost of contraction, patients with COPD display the same metabolic pattern as healthy subjects, suggesting that skeletal muscle energy production is well preserved in these patients.