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

Abstract

[2013][2014][2015][2016][2017][2018] 1999. To further elucidate these population-specific limitations to metabolic rate, we used 31 P-magnetic resonance spectroscopy to study the exercising human gastrocnemius muscle under conditions of varied FI O 2 in sedentary subjects. To test the hypothesis that PCr recovery from submaximal exercise in sedentary subjects is not limited by O 2 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 FI O 2 (0.10, 0.21, and 1.00). PCr recovery time constants were significantly longer in hypoxia (47.0 Ϯ 3.2 s), but there was no difference between hyperoxia (31.8 Ϯ 1.9 s) and normoxia (30.0 Ϯ 2.1 s) (mean Ϯ 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 O 2 availability in normoxia. Additionally, the significant elongation of PCr recovery in these subjects in hypoxia illustrates the reliance on O 2 supply at the other end of the O2 availability spectrum in both sedentary and active populations. oxidative capacity; mitochondria; exercise; intracellular oxygenation; 31-phosphorous-magnetic resonance spectroscopy THERE IS A GROWING APPRECIATION of the concept that O 2 supply and demand limitations to maximal metabolic rate are dependent on the population studied (4, 26, 31). However, it should be noted that the preponderance of data have been collected from physically active or endurance-trained subjects who reveal O 2 supply dependence at maximal O 2 uptake (V O 2 max ). The supply of O 2 and its utilization by skeletal muscle is a tightly interwoven process that cannot easily be assessed by a single measurement. Although 31 P-magnetic resonance spectroscopy (MRS) measurements of phosphocreatine (PCr) recovery provide an accurate measure of skeletal muscle oxidative metabolism (2,11,15,17), alone this methodology is unable to discern limitation caused by O 2 supply from that of mitochondrial O 2 demand.However, the combination of PCr recovery measurement under conditions of altered O 2 availability, manipulated by varying the inspired O 2 fraction (FI O 2 ), has been utilized to demonstrate that, in exercise-trained humans, under normoxic conditions, O 2 availability limits maximal oxidative rate (7). The practical implication of these data is that PCr recovery measurements alone should be interpreted with caution because differences in PCr recovery between subjects may not be due to metabolic limitations (1, 5, 19) but rather to limitations in O 2 supply (30). To solidify this unique approach of combining manipulations in O 2 availability with PCr recovery, it is important to demonstrate that this methodology is able to determine the difference between mitochondrial limitation vs. O 2 supply limitation across subje...

Reduced muscle oxidative capacity is independent of O2 availability in elderly people

“…2). These results are consistent with the unaltered postexercise PCr recovery kinetics (Haseler et al 2004) and leg VO 2max (Cardus et al 1998) in hyperoxia compared to normoxia previously reported in young sedentary subjects and extend these findings to the elderly. These findings, therefore, reveal that the maximal rate of mitochondrial ATP synthesis in the calf muscle is determined by mitochondrial capacity rather than O 2 supply in both young and elderly sedentary individuals.…”

“…For instance, Pedersen et al (1999) reported diminished leg blood flow and a trend for a lower maximal O 2 consumption during one-leg knee extension exercise in hyperoxia compared to normoxia (Pedersen et al 1999). Interestingly, similar to the present study, Haseler et al (2004) also reported a slight increase in the PCr recovery time constant in hyperoxia compared to normoxia in young untrained individuals, although this difference was less marked (Haseler et al 2004). It cannot be ruled out that breathing hyperoxic gas mixture during our plantar flexion exercise may have resulted in hyperoxic vasoconstriction, thus compromising to some extent O 2 availability in the young untrained subjects.…”

“…Specifically, as O 2 supply appears to slow pulmonary O 2 consumption kinetics at the onset of contractions in older individuals (DeLorey et al 2007), it could be hypothesized that O 2 availability will also limit the recovery kinetics of PCr. Therefore, unlike their sedentary younger counterparts (Haseler et al 2004), an improved O 2 availability induced by breathing a hyperoxic gas mixture could accelerate the PCr recovery time constant in the older sedentary subjects. Alternatively, it could be hypothesized that, if despite the reduction in O 2 transport, intracellular PO 2 in older adults is maintained above a critical value (Wilson et al 1977;Haseler et al 2007), PCr recovery kinetics could be limited by mitochondrial capacity to generate ATP such that hyperoxia will not affect the PCr recovery time constant.…”

Oxygen availability and PCr recovery rate in untrained human calf muscle: evidence of metabolic limitation in normoxia

“…It is upon the later unanswered question that we now focus our experiments to initially provide a benchmark for the normal healthy balance between O 2 supply and demand in ambient O 2 in untrained skeletal muscle and ultimately better understand the numerous pathologies that alter O 2 availability and metabolism either individually or in unison. Unlike maximal exercise, an advantage of assessing maximal muscle oxidative metabolism by PCr recovery from submaximal exercise is the low level of stress involved, making it suitable for studying oxidative rate during exercise under conditions of severe hypoxia, and in subjects who are unaccustomed to strenuous exercise due to inactivity, aging, or debilitating pathologies (10,14,18).Consequently, we sought to identify the critical Sa O 2 below which maximal oxidative rate would be reduced in sedentary humans by using arterial oximetry, serial reductions in O 2 availability from normoxia (FI O 2 ϭ 0.21, 0.15, 0.12, and 0.1), and 31 P magnetic resonance spectroscopy (MRS) to measure PCr recovery from plantar flexion exercise. The specific hypothesis tested was that metabolic capacity in untrained human skeletal muscle is perfectly matched to ambient O 2 availability, and hence even a modest reduction in Sa O 2 will significantly impact the maximal mitochondrial oxidative rate, as measured by PCr recovery.…”

“…It is upon the later unanswered question that we now focus our experiments to initially provide a benchmark for the normal healthy balance between O 2 supply and demand in ambient O 2 in untrained skeletal muscle and ultimately better understand the numerous pathologies that alter O 2 availability and metabolism either individually or in unison. Unlike maximal exercise, an advantage of assessing maximal muscle oxidative metabolism by PCr recovery from submaximal exercise is the low level of stress involved, making it suitable for studying oxidative rate during exercise under conditions of severe hypoxia, and in subjects who are unaccustomed to strenuous exercise due to inactivity, aging, or debilitating pathologies (10,14,18).…”