Skeletal muscle oxidative metabolism in sedentary humans: 31P-MRS assessment of O2 supply and demand limitations

2004 ◽  
Vol 97 (3) ◽  
pp. 1077-1081 ◽  
Author(s):  
Luke J. Haseler ◽  
Alexander P. Lin ◽  
Russell S. Richardson

Previously, it was demonstrated in exercise-trained humans that phosphocreatine (PCr) recovery is significantly altered by fraction of inspired O2 (FiO2), suggesting that in this population under normoxic conditions, O2 availability limits maximal oxidative rate. Haseler LJ, Hogan ML, and Richardson RS. J Appl Physiol 86: 2013–2018, 1999. To further elucidate these population-specific limitations to metabolic rate, we used 31P-magnetic resonance spectroscopy to study the exercising human gastrocnemius muscle under conditions of varied FiO2 in sedentary subjects. To test the hypothesis that PCr recovery from submaximal exercise in sedentary subjects is not limited by O2 availability, but rather by their mitochondrial capacity, six sedentary subjects performed three bouts of 6-min steady-state submaximal plantar flexion exercise followed by 5 min of recovery while breathing three different FiO2 (0.10, 0.21, and 1.00). PCr recovery time constants were significantly longer in hypoxia (47.0 ± 3.2 s), but there was no difference between hyperoxia (31.8 ± 1.9 s) and normoxia (30.0 ± 2.1 s) (mean ± SE). End-exercise pH was not significantly different across treatments. These results suggest that the maximal muscle oxidative rate of these sedentary subjects, unlike their exercise-trained counterparts, is limited by mitochondrial capacity and not O2 availability in normoxia. Additionally, the significant elongation of PCr recovery in these subjects in hypoxia illustrates the reliance on O2 supply at the other end of the O2 availability spectrum in both sedentary and active populations.

1999 ◽  
Vol 86 (6) ◽  
pp. 2013-2018 ◽  
Author(s):  
Luke J. Haseler ◽  
Michael C. Hogan ◽  
Russell S. Richardson

In skeletal muscle, phosphocreatine (PCr) recovery from submaximal exercise has become a reliable and accepted measure of muscle oxidative capacity. During exercise, O2 availability plays a role in determining maximal oxidative metabolism, but the relationship between O2 availability and oxidative metabolism measured by31P-magnetic resonance spectroscopy (MRS) during recovery from exercise has never been studied. We used 31P-MRS to study exercising human gastrocnemius muscle under conditions of varied fractions of inspired O2 [Formula: see text]) to test the hypothesis that varied O2availability modulates PCr recovery from submaximal exercise. Six male subjects performed three bouts of 5-min steady-state submaximal plantar flexion exercise followed by 5 min of recovery in a 1.5-T magnet while breathing three different[Formula: see text] concentrations (0.10, 0.21, and 1.00). Under each[Formula: see text] treatment, the PCr recovery time constants were significantly different, being longer in hypoxia [33.5 ± 4.1 s (SE)] and shorter in hyperoxia (20.0 ± 1.8 s) than in normoxia (25.0 ± 2.7 s) ( P ≤ 0.05). End-exercise pH was not significantly different among the three treatments (7.08 ± 0.01 for 0.10, 7.04 ± 0.01 for 0.21, and 7.04 ± 0.02 for 1.00). These results demonstrate that PCr recovery is significantly altered by[Formula: see text] and suggest that, after submaximal exercise, PCr recovery, under normoxic conditions, is limited by O2 availability.


2005 ◽  
Vol 3 (Special_Issue_2) ◽  
pp. 235-244 ◽  
Author(s):  
Norihide Sugisaki ◽  
Hiroaki Kanehisa ◽  
Yasuo Kawakami ◽  
Tetsuo Fukunaga

2016 ◽  
Vol 29 (12) ◽  
pp. 1825-1834 ◽  
Author(s):  
Ladislav Valkovič ◽  
Marek Chmelík ◽  
Martin Meyerspeer ◽  
Borjan Gagoski ◽  
Christopher T. Rodgers ◽  
...  

1998 ◽  
Vol 85 (4) ◽  
pp. 1457-1463 ◽  
Author(s):  
Luke J. Haseler ◽  
Russell S. Richardson ◽  
John S. Videen ◽  
Michael C. Hogan

There is evidence that the concentration of the high-energy phosphate metabolites may be altered during steady-state submaximal exercise by the breathing of different fractions of inspired O2([Formula: see text]). Whereas it has been suggested that these changes may be the result of differences in time taken to achieve steady-state O2 uptake (V˙o 2) at different[Formula: see text] values, we postulated that they are due to a direct effect of O2 tension. We used31P-magnetic resonance spectroscopy during constant-load, steady-state submaximal exercise to determine 1) whether changes in high-energy phosphates do occur at the sameV˙o 2 with varied[Formula: see text] and 2) that these changes are not due to differences in V˙o 2onset kinetics. Six male subjects performed steady-state submaximal plantar flexion exercise [7.2 ± 0.6 (SE) W] for 10 min while lying supine in a 1.5-T clinical scanner. Magnetic resonance spectroscopy data were collected continuously for 2 min before exercise, 10 min during exercise, and 6 min during recovery. Subjects performed three different exercise bouts at constant load with the[Formula: see text] switched after 5 min of the 10-min exercise bout. The three exercise treatments were 1)[Formula: see text] of 0.1 switched to 0.21, 2)[Formula: see text] of 0.1 switched to 1.00, and 3)[Formula: see text] of 1.00 switched to 0.1. For all three treatments, the[Formula: see text] switch significantly ( P ≤ 0.05) altered phosphocreatine: 1) 55.5 ± 4.8 to 67.8 ± 4.9% (%rest); 2) 59.0 ± 4.3 to 72.3 ± 5.1%; and 3) 72.6 ± 3.1 to 64.2 ± 3.4%, respectively. There were no significant differences in intracellular pH for the three treatments. The results demonstrate that the differences in phosphocreatine concentration with varied [Formula: see text] are not the result of different V˙o 2onset kinetics, as this was eliminated by the experimental design. These data also demonstrate that changes in intracellular oxygenation, at the same work intensity, result in significant changes in cell homeostasis and thereby suggest a role for metabolic control by O2 even during submaximal exercise.


1999 ◽  
Vol 277 (1) ◽  
pp. R173-R180 ◽  
Author(s):  
Paul A. Molé ◽  
Youngran Chung ◽  
Tuan Khanh Tran ◽  
Napapon Sailasuta ◽  
Ralph Hurd ◽  
...  

The present study evaluated whether intracellular partial pressure of O2 ([Formula: see text]) modulates the muscle O2 uptake (V˙o 2) as exercise intensity increased. Indirect calorimetry followedV˙o 2, whereas nuclear magnetic resonance (NMR) monitored the high-energy phosphate levels, intracellular pH, and intracellular[Formula: see text] in the gastrocnemius muscle of four untrained subjects at rest, during plantar flexion exercise with a constant load at a repetition rate of 0.75, 0.92, and 1.17 Hz, and during postexercise recovery.V˙o 2 increased linearly with exercise intensity and peaked at 1.17 Hz (15.1 ± 0.37 watts), when the subjects could maintain the exercise for only 3 min.V˙o 2 reached a peak value of 13.0 ± 1.59 ml O2 ⋅ min−1 ⋅ 100 ml leg volume−1. The31P spectra indicated that phosphocreatine decreased to 32% of its resting value, whereas intracellular pH decreased linearly with power output, reaching 6.86. Muscle ATP concentration, however, remained constant throughout the exercise protocol. The 1H NMR deoxymyoglobin signal, reflecting the cellular[Formula: see text], decreased in proportion to increments in power output andV˙o 2. At the highest exercise intensity and peakV˙o 2, myoglobin was ∼50% desaturated. These findings, taken together, suggest that the O2 gradient from hemoglobin to the mitochondria can modulate the O2flux to meet the increasedV˙o 2 in exercising muscle, but declining cellular [Formula: see text]during enhanced mitochondrial respiration suggests that O2 availability is not limitingV˙o 2 during exercise.


2013 ◽  
Vol 115 (12) ◽  
pp. 1757-1766 ◽  
Author(s):  
Terence E. Ryan ◽  
W. Michael Southern ◽  
Mary Ann Reynolds ◽  
Kevin K. McCully

The purpose of this study was to cross-validate measurements of skeletal muscle oxidative capacity made with near-infrared spectroscopy (NIRS) measurements to those made with phosphorus magnetic resonance spectroscopy (31P-MRS). Sixteen young (age = 22.5 ± 3.0 yr), healthy individuals were tested with both 31P-MRS and NIRS during a single testing session. The recovery rate of phosphocreatine was measured inside the bore of a 3-Tesla MRI scanner, after short-duration (∼10 s) plantar flexion exercise as an index of skeletal muscle oxidative capacity. Using NIRS, the recovery rate of muscle oxygen consumption was also measured using repeated, transient arterial occlusions outside the MRI scanner, after short-duration (∼10 s) plantar flexion exercise as another index of skeletal muscle oxidative capacity. The average recovery time constant was 31.5 ± 8.5 s for phosphocreatine and 31.5 ± 8.9 s for muscle oxygen consumption for all participants ( P = 0.709). 31P-MRS time constants correlated well with NIRS time constants for both channel 1 (Pearson's r = 0.88, P < 0.0001) and channel 2 (Pearson's r = 0.95, P < 0.0001). Furthermore, both 31P-MRS and NIRS exhibit good repeatability between trials (coefficient of variation = 8.1, 6.9, and 7.9% for NIRS channel 1, NIRS channel 2, and 31P-MRS, respectively). The good agreement between NIRS and 31P-MRS indexes of skeletal muscle oxidative capacity suggest that NIRS is a valid method for assessing mitochondrial function, and that direct comparisons between NIRS and 31P-MRS measurements may be possible.


2017 ◽  
Vol 313 (1) ◽  
pp. E94-E104 ◽  
Author(s):  
Gwenael Layec ◽  
Corey R. Hart ◽  
Joel D. Trinity ◽  
Oh-Sung Kwon ◽  
Matthew J. Rossman ◽  
...  

Patients with chronic obstructive pulmonary disease (COPD) experience a delayed recovery from skeletal muscle fatigue following exhaustive exercise that likely contributes to their progressive loss of mobility. As this phenomenon is not well understood, this study sought to examine postexercise peripheral oxygen (O2) transport and muscle metabolism dynamics in patients with COPD, two important determinants of muscle recovery. Twenty-four subjects, 12 nonhypoxemic patients with COPD and 12 healthy subjects with a sedentary lifestyle, performed dynamic plantar flexion exercise at 40% of the maximal work rate (WRmax) with phosphorus magnetic resonance spectroscopy (31P-MRS), near-infrared spectroscopy (NIRS), and vascular Doppler ultrasound assessments. The mean response time of limb blood flow at the offset of exercise was significantly prolonged in patients with COPD (controls: 56 ± 27 s; COPD: 120 ± 87 s; P < 0.05). In contrast, the postexercise time constant for capillary blood flow was not significantly different between groups (controls: 49 ± 23 s; COPD: 51 ± 21 s; P > 0.05). The initial postexercise convective O2 delivery (controls: 0.15 ± 0.06 l/min; COPD: 0.15 ± 0.06 l/min) and the corresponding oxidative adenosine triphosphate (ATP) demand (controls: 14 ± 6 mM/min; COPD: 14 ± 6 mM/min) in the calf were not significantly different between controls and patients with COPD ( P > 0.05). The phosphocreatine resynthesis time constant (controls: 46 ± 20 s; COPD: 49 ± 21 s), peak mitochondrial phosphorylation rate, and initial proton efflux were also not significantly different between groups ( P > 0.05). Therefore, despite perturbed peripheral hemodynamics, intracellular O2 availability, proton efflux, and aerobic metabolism recovery in the skeletal muscle of nonhypoxemic patients with COPD are preserved following plantar flexion exercise and thus are unlikely to contribute to the delayed recovery from exercise in this population.


1994 ◽  
Vol 77 (5) ◽  
pp. 2169-2176 ◽  
Author(s):  
T. J. Barstow ◽  
S. D. Buchthal ◽  
S. Zanconato ◽  
D. M. Cooper

The purpose of this study was to evaluate the consequences of non-linear changes in phosphocreatine (PCr) and pH during incremental calf exercise on estimates of ADP and cytosolic free energy of ATP hydrolysis (delta GATP). Six subjects performed incremental plantar flexion exercise on a treadle ergometer while muscle P(i) metabolism (PCr, P(i), ATP) and pH were followed using 31P-nuclear magnetic resonance spectroscopy. Changes in ADP and delta GATP were estimated with the assumption that there was equilibrium of the creatine kinase reaction and homogeneous tissue metabolite pools. All six subjects showed a threshold for onset of cellular acidosis that occurred on average at 47.3 +/- 12.7% of peak work rate (PWR). In five of the six subjects, PCr and P(i) showed accelerated rates of change above the threshold for onset of cellular acidosis. In all six subjects, ADP, when correctly calculated considering changes in pH, rose in a curvilinear fashion that was well described by a Michaelis-Menten hyperbola through 60–100% of PWR, with a mean apparent Michaelis-Menten constant of 43.1 +/- 17.1 microM ADP and a predicted maximal oxidative rate at PCr = 0, which was 241 +/- 94% of PWR. delta GATP rose linearly with work rate from -62.9 +/- 1.8 kJ/mol during unloaded treadling to -55.0 +/- 1.8 kJ/mol at PWR. If we assume a linear O2 uptake-to-work rate relationship, these results are most consistent with control of respiration being exerted through delta GATP under these conditions (incremental exercise by human calf muscle).(ABSTRACT TRUNCATED AT 250 WORDS)


1999 ◽  
Vol 86 (4) ◽  
pp. 1367-1373 ◽  
Author(s):  
Michael C. Hogan ◽  
Russell S. Richardson ◽  
Luke J. Haseler

The purpose of this study was to use31P-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([Formula: see text]). We hypothesized that lower [Formula: see text]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 [Formula: see text] (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[Formula: see text] was increased. Muscle phosphocreatine (PCr) concentration, Pi concentration, and pH at exhaustion were not significantly different among the three[Formula: see text] 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[Formula: see text] condition compared with the other two [Formula: see text]conditions. These results demonstrate that exhaustion during all[Formula: see text] occurred when a particular intracellular environment was acheived and suggest that during the lowest [Formula: see text]condition, the greater PCr hydrolysis and intracellular acidosis at submaximal workloads may have contributed to the significantly earlier time to exhaustion.


2007 ◽  
Vol 293 (5) ◽  
pp. R2046-R2051 ◽  
Author(s):  
Luke J. Haseler ◽  
Alexander Lin ◽  
Jan Hoff ◽  
Russell S. Richardson

In contrast to their exercise-trained counterparts, the maximal oxidative rate of skeletal muscle in sedentary humans appears not to benefit from supplemental O2 availability but is impacted by severe hypoxia, suggesting a metabolic limitation either at or below ambient O2 levels. However, the critical level of O2 availability at which maximal metabolic rate is reduced in sedentary humans is unknown. Using 31P magnetic resonance spectroscopy and arterial oximetry, phosphocreatine (PCr) recovery kinetics and arterial oxygenation were assessed in six sedentary subjects performing 5-min bouts of plantar flexion exercise followed by 6 min of recovery. Each trial was repeated while breathing one of four different fractions of inspired O2 (FIO2) (0.10, 0.12, 0.15, and 0.21). The PCr recovery rate constant (a marker of oxidative capacity) was unaffected by reductions in FIO2, remaining at a value of 1.5 ± 0.2 min−1 until arterial O2 saturation (SaO2) fell to less than ∼92%, the average value reached breathing an FIO2 of 0.15. Below this SaO2, the PCr rate constant fell significantly by 13 and 31% to 1.3 ± 0.2 and 1.0 ± 0.2 min−1 ( P < 0.05) as SaO2 was reduced to 82 ± 3 and 77 ± 2%, respectively. In conclusion, this study has revealed that O2 availability does not impact maximal oxidative rate in sedentary humans until the O2 level falls well below that of ambient air, indicating a metabolic limitation in normoxia.


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