Relationships between in vivo and in vitro measurements of metabolism in young and old human calf muscles

Abstract

This study compared in vivo measurements of muscle metabolism in humans with magnetic resonance spectroscopy (MRS) and in vitro analysis of biopsies. Healthy subjects [4 young males, 28.2 +/- 6.8 (SD) yr, and 6 older subjects (5 males, 1 female), 66 +/- 6.0 yr] performed a maximal cycle ergometer test, and MRS measurements of the calf muscles and needle biopsies of the lateral gastrocnemius were performed. Biopsies were analyzed for fiber type and citrate synthase (CS) activity. MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr), ATP, and pH were made using a 1.8-T 78-cm clear-bore magnet-and-spectrometer system. Two or three 5-min bouts of plantar flexion were performed against variable resistance to deplete PCr levels to 50% of resting values (mean end pH 6.99). PCr values during recovery were fit to an exponential curve, and the rate constant (PCrrate) was calculated. PCrrate was used as an index of oxidative metabolism. Older subjects had lower peak O2 uptake (VO2 peak) values (19.2 +/- 5.6 vs. 49.5 +/- 8.1 ml O2.min-1 x kg-1), CS activities (16 +/- 2.8 vs. 25 +/- 2.6 mmol.kg wet wt-1 x min-1), and PCrrate values (25.3 +/- 8. vs. 37.5 +/- 5.3 mmol PCr.kg wet wt-1.min-1) than young subjects. PCrrate correlated with CS activity, and both PCrrate and CS activity correlated with VO2 peak (P < 0.05). No correlations were found between percent fiber type and PCrrate, CS activity, and VO2 peak. These results support studies that showed decreases in muscle metabolism with age in healthy humans and show a good correlation between in vivo and in vitro measurements of oxidative metabolism.

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

“…The normoxic PCr values from that study (25 .0 Ϯ 2.7 s) are shorter than those reported here for the sedentary subjects (30.0 Ϯ 2.1 s). This is consistent with previous studies showing shorter PCr values in exercise-trained individuals due to the increased oxidative capacity of the subjects (14,16,32). The assessment of an individual's response to the manipulations in O 2 availability used here and previously (7) helps to move the PCr measurement from a subjective to an objective evaluation of the O 2 supply and demand limitations to metabolic capacity.…”

“…PCr recovery is a useful measure of skeletal muscle oxidative capacity and is dependent on mitochondrial respiratory function (3,11). A further advantage of the measure is that PCr recovery does not require a correction for active muscle mass (10,16) and is independent of the work level (17), provided that muscle intracellular pH does not fall severely (2). Thus the measurement of PCr recovery has proven useful in determining the oxidative capacity of skeletal muscle in a variety of conditions (12,15,30,32).…”

Muscle strength mediates the relationship between mitochondrial energetics and walking performance

“…Physical exercise is the only intervention thus far that has been shown to significantly improve muscle strength in older individuals (Latham et al ., 2004). In addition, there is literature support for the positive role of resistance exercise and elevated levels of aerobic physical activity on mitochondrial content and function in the elderly (McCully et al ., 1993; Brierley et al ., 1996; Jubrias et al ., 2001), presenting a coherent picture with our current results. Together, these studies provide strong support for exploration of such interventions as an important prescriptive step in retaining functional mobility and independence with aging.…”

“…This method is reproducible (McCully et al ., 2009), can be focused to a specific, single muscle (McCully et al ., 1993), is not affected by postural or balance impairments, and has been validated against in vitro techniques (McCully et al ., 1993; Conley et al ., 2000). Muscular oxidative capacity is indexed by the postexercise PCr resynthesis rate constant, or k PCr , which is determined by monitoring the mono‐exponential recovery of PCr (Meyer, 1988) in the rest period following an exercise‐induced depletion.…”

Lower Mitochondrial Energy Production of the Thigh Muscles in Patients With Low‐Normal Ankle‐Brachial Index

“…This is taken as an index of in vivo muscle oxidative phosphorylation capacity, as there are minimal other energy demands during this resting period. k PCr resynthesis is primarily considered a function of maximum mitochondrial ATP production with no or minimal contribution of anaerobic metabolism 15, 16, 17, 18, 19, 20. The percentage of PCr depletion was calculated as the decrease in the PCr peak area from pre‐exercise PCrbaseline to PCr0 21, 22.…”