Resting Vastus Lateralis Research Articles

Durability of the moderate-to-heavy-intensity transition is related to the effects of prolonged exercise on severe-intensity performance

PurposePower output at the moderate-to-heavy-intensity transition decreases during prolonged exercise, and resilience to this has been termed ‘durability’. The purpose of this study was to assess the relationship between durability and the effect of prolonged exercise on severe-intensity performance, and explore intramuscular correlates of durability.MethodsOn separate days, 13 well-trained cyclists and triathletes (V̇O2peak, 57.3 ± 4.8 mL kg−1 min−1; training volume, 12 ± 2.1 h week−1) undertook an incremental test and 5-min time trial (TT) to determine power output at the first ventilatory threshold (VT1) and severe-intensity performance, with and without 150-min of prior moderate-intensity cycling. A single resting vastus lateralis microbiopsy was obtained.ResultsProlonged exercise reduced power output at VT1 (211 ± 40 vs. 198 ± 39 W, ∆ -13 ± 16 W, ∆ -6 ± 7%, P = 0.013) and 5-min TT performance (333 ± 75 vs. 302 ± 63 W, ∆ -31 ± 41 W, ∆ -9 ± 10%, P = 0.017). The reduction in 5-min TT performance was significantly associated with durability of VT1 (rs = 0.719, P = 0.007). Durability of VT1 was not related to vastus lateralis carnosine content, citrate synthase activity, or complex I activity (P > 0.05).ConclusionThese data provide the first direct support that durability of the moderate-to-heavy-intensity transition is an important performance parameter, as more durable athletes exhibited smaller reductions in 5-min TT performance following prolonged exercise. We did not find relationships between durability and vastus lateralis carnosine content, citrate synthase activity, or complex I activity.

Skeletal muscle proteins involved in fatty acid transport influence fatty acid oxidation rates observed during exercise.

Several proteins are implicated in transmembrane fatty acid transport. The purpose of this study was to quantify the variation in fatty acid oxidation rates during exercise explained by skeletal muscle proteins involved in fatty acid transport. Seventeen endurance-trained males underwent a (i) fasted, incremental cycling test to estimate peak whole-body fatty acid oxidation rate (PFO), (ii) resting vastus lateralis microbiopsy, and (iii) 2 h of fed-state, moderate-intensity cycling to estimate whole-body fatty acid oxidation during fed-state exercise (FO). Bivariate correlations and stepwise linear regression models of PFO and FO during 0-30 min (early FO) and 90-120 min(late FO) of continuous cycling were constructed using muscle data. To assess the causal role of transmembrane fatty acid transport in fatty acid oxidation rates during exercise, we measured fatty acid oxidation during in vivo exercise and ex vivo contractions in wild-type and CD36 knock-out mice. We observed a novel, positive association between vastus lateralis FATP1 and PFO and replicated work reporting a positive association between FABPpm and PFO. The stepwise linear regression model of PFO retained CD36, FATP1, FATP4, and FABPpm, explaining ~87% of the variation. Models of early and late FO explained ~61 and ~65% of the variation, respectively. FATP1 and FATP4 emerged as contributors to models of PFO and FO. Mice lacking CD36 had impaired whole-body and muscle fatty acid oxidation during exercise and muscle contractions, respectively. These data suggest that substantial variation in fatty acid oxidation rates during exercise can be explained by skeletal muscle proteins involved in fatty acid transport.

Peak fat oxidation is positively associated with vastus lateralis CD36 content, fed-state exercise fat oxidation, and endurance performance in trained males.

PurposeWhole-body fat oxidation during exercise can be measured non-invasively during athlete profiling. Gaps in understanding exist in the relationships between fat oxidation during incremental fasted exercise and skeletal muscle parameters, endurance performance, and fat oxidation during prolonged fed-state exercise.MethodsSeventeen endurance-trained males underwent a (i) fasted, incremental cycling test to assess peak whole-body fat oxidation (PFO), (ii) resting vastus lateralis microbiopsy, and (iii) 30-min maximal-effort cycling time-trial preceded by 2-h of fed-state moderate-intensity cycling to assess endurance performance and fed-state metabolism on separate occasions within one week.ResultsPFO (0.58 ± 0.28 g.min−1) was associated with vastus lateralis citrate synthase activity (69.2 ± 26.0 μmol.min−1.g−1 muscle protein, r = 0.84, 95% CI 0.58, 0.95, P < 0.001), CD36 abundance (16.8 ± 12.6 μg.g−1 muscle protein, rs = 0.68, 95% CI 0.31, 1.10, P = 0.01), pre-loaded 30-min time-trial performance (251 ± 51 W, r = 0.76, 95% CI 0.40, 0.91, P = 0.001; 3.2 ± 0.6 W.kg−1, r = 0.62, 95% CI 0.16, 0.86, P = 0.01), and fat oxidation during prolonged fed-state cycling (r = 0.83, 95% CI 0.57, 0.94, P < 0.001). Addition of PFO to a traditional model of endurance (peak oxygen uptake, power at 4 mmol.L−1 blood lactate concentration, and gross efficiency) explained an additional ~ 2.6% of variation in 30-min time-trial performance (adjusted R2 = 0.903 vs. 0.877).ConclusionThese associations suggest non-invasive measures of whole-body fat oxidation during exercise may be useful in the physiological profiling of endurance athletes.

Temperate performance and metabolic adaptations following endurance training performed under environmental heat stress.

Endurance athletes are frequently exposed to environmental heat stress during training. We investigated whether exposure to 33°C during training would improve endurance performance in temperate conditions and stimulate mitochondrial adaptations. Seventeen endurance‐trained males were randomly assigned to perform a 3‐week training intervention in 18°C (TEMP) or 33°C (HEAT). An incremental test and 30‐min time‐trial preceded by 2‐h low‐intensity cycling were performed in 18°C pre‐ and post‐intervention, along with a resting vastus lateralis microbiopsy. Training was matched for relative cardiovascular demand using heart rates measured at the first and second ventilatory thresholds, along with a weekly “best‐effort” interval session. Perceived training load was similar between‐groups, despite lower power outputs during training in HEAT versus TEMP (p < .05). Time‐trial performance improved to a greater extent in HEAT than TEMP (30 ± 13 vs. 16 ± 5 W, N = 7 vs. N = 6, p = .04), and citrate synthase activity increased in HEAT (fold‐change, 1.25 ± 0.25, p = .03, N = 9) but not TEMP (1.10 ± 0.22, p = .22, N = 7). Training‐induced changes in time‐trial performance and citrate synthase activity were related (r = .51, p = .04). A group × time interaction for peak fat oxidation was observed (Δ 0.05 ± 0.14 vs. −0.09 ± 0.12 g·min−1 in TEMP and HEAT, N = 9 vs. N = 8, p = .05). Our data suggest exposure to moderate environmental heat stress during endurance training may be useful for inducing adaptations relevant to performance in temperate conditions.

Longitudinal hypertrophic and transcriptional responses to high-load eccentric-concentric vs concentric training in males.

High-load eccentric training reputedly produces greater muscle hypertrophy than concentric training, possibly due to greater loading and/or inflammation. We quantified the temporal impact of combined maximal concentric-eccentric training vs maximal concentric training on muscle cross-sectional area (CSA), volume, and targeted mRNA expression (93 transcripts). Eight recreationally active males (24±5years, BMI 23.5±2.5kg/m2 ) performed 3x30 maximal eccentric isokinetic knee extensions and 2x30 maximal concentric knee extensions in dominant limb (ECC+CON) and 5x30 maximal concentric contractions (CON) in the non-dominant limb for 12weeks (all 90°/s, 3x/wk). Quadriceps muscle CSA and volume were measured at baseline, 28days (d), and 84d in both limbs (3T MRI). Resting vastus lateralis biopsies were obtained from both limbs at baseline, 24hours (h), 7, 28, and 84d for mRNA abundance measurements (RT-PCR microfluidic cards). Work output was greater throughout training in ECC+CON vs CON (20.8±9.7%, P<.001). Muscle CSA increased from baseline in both limbs at 28d (CON 4.3±2.6%, ECC+CON 4.0±1.9%, both P<.001) and 84d (CON 3.9±2.3%, ECC+CON 4.0±3.1%, both P<.001), and muscle volume and isometric strength at 84d (CON 44.8±40.0%, P<.001; ECC+CON 36.9±40.0%, P<.01), but no between-limb differences existed in any parameter. Ingenuity Pathway Analysis identified several cellular functions associated with regulation of muscle mass and metabolism as altered by both modalities at 24h and 7d, but particularly with ECC+CON. However, mRNA responses waned thereafter, regardless of modality. Initial muscle mRNA responses to training did not reflect chronic training-induced hypertrophy. Moreover, ECC+CON did not produce greater hypertrophy than CON, despite greater loading throughout and a differential mRNA response during the initial training week.

Resistance training upregulates skeletal muscle Na+, K+-ATPase content, with elevations in both α1 and α2, but not β isoforms.

The Na+, K+-ATPase (NKA) is important in regulating trans-membrane ion gradients, cellular excitability and muscle function. We investigated the effects of resistance training in healthy young adults on the adaptability of NKA content and of the specific α and β isoforms in human skeletal muscle. Twenty-one healthy young males (22.9 ± 4.6 year; 1.80 ± 0.70 m, 85.1 ± 17.8 kg, mean ± SD) underwent 7 weeks of resistance training, training three times per week (RT, n = 16) or control (CON, n = 5). The training program was effective with a 39% gain in leg press muscle strength (p = 0.001). A resting vastus lateralis muscle biopsy was taken before and following RT or CON and assayed for NKA content ([3H]ouabain binding site content) and NKA isoform (α1, α2, β1, β2) abundances. After RT, each of NKA content (12%, 311 ± 76 vs 349 ± 76 pmol g wet weight-1, p = 0.01), NKA α1 (32%, p = 0.01) and α2 (10%, p < 0.01) isoforms were increased, whereas β1 (p = 0.18) and β2 (p = 0.22) isoforms were unchanged. NKA content and isoform abundances were unchanged during CON. Resistance training increased muscle NKA content through upregulation of both α1 and α2 isoforms, which were independent of β isoform changes. In animal models, modulations in α1 and α2 isoform abundances in skeletal muscle may affect fatigue resistance during exercise, muscle hypertrophy and strength. Whether similar in-vivo functional benefits of these NKA isoform adaptations occurs in human muscle with resistance training remains to be determined.

The Impact Of Age On The Transcriptional And Morphological Profile Of Skeletal Muscle

Aging is associated with many physiological changes that impact physical function. Most notably, older adults experience a progressive loss of skeletal muscle mass and function, termed sarcopenia. A better understanding of the molecular and phenotypical changes associated with advancing age may provide therapeutic targets for interventions to slow the progression of sarcopenia. PURPOSE: To characterize the transcriptional and morphological profile of aging skeletal muscle. METHODS: Resting vastus lateralis muscle biopsies were collected from 9 young (Y; 27±3yr, 179±7cm, 82±10kg, 26±3BMI) and 9 older adults (O; 68±5yr, 172±8cm, 77±19kg, 26±5BMI) following an overnight fast. Whole transcriptome next-generation RNA sequencing was performed on cDNA synthesized from skeletal muscle RNA. Differentially expressed genes (FDR-adjusted P-value ≤ 0.05) were identified through DESeq2 and subjected to bioinformatic analyses using DAVID (v6.8). Skeletal muscle morphology including fiber type, satellite cell (SC) content, and capillarization was assessed through immunofluorescent microscopy RESULTS: In total, 900 differentially expressed genes were identified in the skeletal muscle of O versus Y (+1.5 fold change = 213; -1.5 fold change = 127). DAVID functional analyses indicated that aging was associated with functions related to glycogen metabolism, amino acid metabolism, ubiquitination, and transition between fast and slow fibers. Consistent with the latter, a significant difference (P=0.048) in myosin heavy chain (MyHC) fiber type profile was identified (Y = MyHCI: 29±4%, MyHCII: 71±4%; O = MyHCI: 46±7%, MyHCII: 54±7%). Moreover, aging was associated with a numerical reduction in SC specific to MyHCI (Y = 0.13±0.02, O = 0.07±0.02 SC/MyHCI fiber, P=0.07) but not MyHCII fibers (Y=0.12±0.03, O=0.08±0.02 P=0.373). Independent of fiber type, capillaries per fiber was significantly lower (P=0.015) in O (1.53±0.34) vs. Y (4.59±0.85). CONCLUSION: Advancing age is associated with changes in the transcriptional and morphological profile of skeletal muscle. These findings highlight potential therapeutic targets for the preservation of skeletal muscle mass and function with advancing age. Supported by a JumpStart Grant, CHS, ASU.

Relationship Of Glucose Kinetics With Exercise Capacity, Body Composition, And Mitochondrial Function With Aging

Aging is commonly associated with decreases in aerobic capacity, skeletal muscle mass and function, as well as metabolic dysregulation including insulin resistance. PURPOSE: We sought to investigate relationships between these aforementioned hallmark traits of aging. METHODS: Young healthy adults (24-34 years; n=16; 7F/9M; BMI: 25±3 kg/m2) and older adults (65-79 years; n=39; 20F/19M; BMI: 27±4 kg/m2) were recruited as a part of this investigation. Subjects completed a graded maximal exercise test (VO2peak) on a treadmill, a dual-energy X-ray absorptiometry scan, measurement of single-leg knee extension power, a mixed meal tolerance test upon which blood glucose was monitored throughout the next 5 hours, and a resting vastus lateralis biopsy to measure ATP production from permeabilized muscle fibers. RESULTS: Young had a 38% greater aerobic capacity and 45% greater knee extensor maximal power/lean mass. Fasting plasma glucose was lower (P<0.05) in young (86±7 mg/dL vs. 93±8 mg/dL in young and old, respectively), as well as young had 31% lower plasma glucose area above baseline (AAB) in response to the mixed meal tolerance test compared to old (P<0.05). No differences between young and old were observed in lean body mass, fasting plasma insulin, or maximal mitochondrial ATP production (state III). Interestingly, AAB was not significantly correlated with phenotypic characteristics (BMI or lean body mass), fasting plasma glucose or insulin, or maximal ATP production. However, AAB was significantly (P<0.05) inversely correlated with VO2peak relative to body mass (r = -0.38) and knee extensor power/lean mass (r = -0.47). CONCLUSIONS: These data suggest that glucose tolerance may be a function of skeletal muscle quality rather than total lean mass. However, the inverse relationship with AAB and measurements of whole body functional tests do not appear to be related mitochondrial energy production, suggesting the need for further mechanistic investigations. Supported by NIH grant R01AG054454

Skeletal Muscle Fiber Type and Morphology in a Middle-Aged Elite Male Powerlifter Using Anabolic Steroids

Powerlifting regularly exposes athletes to extreme stimuli such as chronic heavy resistance training (HRT), and many powerlifters choose to augment their performance with anabolic–androgenic steroids (AAS). However, little is known about the myocellular adaptations that occur from long-term HRT and AAS use, especially into middle age. We were presented with the unique opportunity to study muscle cells from an elite-level powerlifter (EPL; age 40 years) with ≥ 30 years of HRT experience and ≥ 15 years of AAS use. The purpose of this case study was to identify myocellular characteristics [myosin heavy chain (MHC) fiber type, fiber size, and myonuclear content] in EPL, as well as compare these data to existing literature. The participant underwent a resting vastus lateralis muscle biopsy and single fibers were analyzed for MHC content via SDS-PAGE. A subset of fibers underwent MHC-specific imaging analysis via confocal microscopy to identify cell size (cross-sectional area, CSA) and myonuclear domain (MND) size. MHC fiber type distribution was 9% I, 12% I/IIa, 79% IIa, and 0% other isoforms. This pure MHC IIa (fast-twitch) fiber content was amongst the highest reported in the literature. Imaging analysis of MHC IIa fibers revealed a mean CSA of 4218 ± 933 μm2 and MND of 12,548 ± 3181 μm3. While the fast-twitch fiber CSA was comparable to values in previous literature, mean MND was smaller than has been reported in untrained men, implying greater capacity for growth and repair. These findings showcase the unique muscle cell structure of an elite powerlifter, extending the known physiological limits of human muscle size and strength.

Chronic effects of high-intensity interval training on postprandial lipemia in healthy men.

The aim of this study was to determine the chronic (≥72 h postexercise) effects of high-intensity interval training (HIIT) on postprandial lipemia and metabolic markers in healthy volunteers. Eight physically active young men (mean ± SD: age 22 ± 3 yr, height 1.77 ± 0.07 m, body mass 67.7 ± 6.2 kg) underwent two 6-h mixed-meal tolerance tests and resting vastus lateralis muscle biopsies before the first session and ≥72 h after the final session of 4 wk of HIIT [16 sessions in total; 10 × 60-s bouts of cycling at 90% maximal oxygen uptake (V̇o2max), interspersed with 60-s intervals at 45% V̇o2max]. Arterialized and deep venous blood samples from across the forearm, brachial artery blood flow measurements, and whole-body indirect calorimetry data were obtained before, and at regular intervals for 6 h after, consumption of a standardized mixed meal. The main findings revealed that, when assessed ≥72 h postexercise, postprandial free fatty acid (FFA) uptake across the forearm was increased in response to exercise training (P = 0.025). However, 4 wk of HIIT did not alter fasting or postprandial circulating triglyceride concentrations or their tissue uptake, despite a 10.2% ± 7.7% improvement in V̇o2max (P = 0.004). Protein content of adipose triglyceride lipase in the vastus lateralis at rest was reduced by 25% ± 21% (P = 0.01). Collectively, these findings suggest that 4 wk of HIIT enhances postprandial clearance of FFA when assessed ≥72 h postexercise but does not confer persisting (training) adaptations in postprandial triglyceridemia.NEW & NOTEWORTHY When assessed ≥72 h after the last exercise session, 4 wk of high-intensity interval training (HIIT) did not improve triglyceridemia but enhanced free fatty acid uptake into muscle with a concurrent reduction in skeletal muscle adipose triglyceride lipase protein content. This suggests that previously reported acute reductions in postprandial triglyceridemia following a single bout of HIIT do not translate to sustained improvements after 4 wk of HIIT, supporting the concept of frequent exercise for the maintenance of lipemic control.

Resting Muscle Shear Modulus Measured With Ultrasound Shear-Wave Elastography as an Alternative Tool to Assess Muscle Fatigue in Humans.

The aim of this study was to investigate the time course of the resting vastus lateralis (VL) muscle shear elastic modulus (μ) measured with ultrasound shear-wave elastography during repetition of isometric maximal voluntary contractions (MVCs) of the knee extensors (KE). Fifteen well-trained young males repeated 60 5-s isometric MVCs. Evoked electrical stimulations and the VLμ were measured every ten MVCs at rest. The resting VLμ significantly decreased (−34.7 ± 6.7%; P < 0.001) by the end of the fatigue protocol. There was also a 38.4 ± 12.6 % decrease in MVC after exercise (P < 0.001). The potentiated doublet and single twitch torque amplitudes and properties were significantly modified by the end of exercise (P < 0.001). This study shows the time course of the resting VLμ during the repetition of maximal voluntary fatiguing exercise of the KE muscles. The decrease of the resting VLμ could directly affect the force transmission capabilities accounting for peripheral fatigue.

Reliability of resting intramuscular fiber conduction velocityevaluation.

Characterization of the least number of muscle fibers analyzed for a quick and reliable, evaluation of intramuscular fiber conduction velocity (MFCV) is of importance for sport scientists. The aim of this study was to evaluate the reliability of vastus lateralis' intramuscular MFCV measuring either 25 or 50 different muscle fibers per participant, as well as to compare intramuscular MFCV measured in 25 (C25 ), 50 (C50 ), or 140 (C140 ) muscle fibers. Resting vastus lateralis' MFCV was measured in 21 young healthy males (age 22.1±2.4years) using intramuscular microelectrodes in different days. Test-retest reliability of MFCV's parameters was calculated for C25 and C50 , while MFCV was compared among C25 , C50 , and C140 . Significant differences of MFCV parameters were observed between C25 condition and those of C50 and C140 . The differences in MFCV values between conditions C50 and C140 were non-significant. A close correlation was found for MFCV between C50 and C140 (r=0.884-0.988, P=.000). All reliability measures of MFCV measured with 50 fibers were high (eg, ICC=0.813-0.980, P=.000), in contrast to C25 (eg, ICC=0.023-0.580 P>.05). In conclusion, an average of 50 different fibers per subject is sufficient to provide a quick and reliable intramuscular evaluation of vastus lateralis MFCV.

Muscle Fiber Conduction Velocity, Muscle Fiber Composition, and Power Performance.

The aim of this study was to explore the relationship between muscle fiber conduction velocity (MFCV), fiber type composition, and power performance in participants with different training background. Thirty-eight young males with different training background participated: sedentary (n = 10), endurance runners (n = 9), power trained (n = 10), and strength trained (n = 9). They performed maximal countermovement jumps (CMJ) and maximal isometric leg press for the measurement of the rate of force development (RFD). Resting vastus lateralis MFCV was measured with intramuscular microelectrodes on a different occasion, whereas muscle fiber type and cross-sectional area (CSA) of vastus lateralis were evaluated through muscle biopsies 1wk later. MFCV, CMJ power, RFD, and % CSA of type II and type IIx fibers were higher for the power-trained group (P < 0.001). No difference was found between sedentary participants and endurance runners in these variables, but both of these groups performed worse than strength/power participants. Close correlations were found between MFCV and fiber CSA as well as the % CSA of all fiber types as well as with RFD and CMJ power (r = 0.712-0.943, P < 0.005). Partial correlations revealed that the % CSA of IIx fibers dictates a large part of the correlation between MFCV and RFD, power performance. Significant models for the prediction of the % CSA of type IIa and type II as well as the CSA of all muscle fibers based upon MFCV, RFD, and CMJ were revealed (P = 0.000). MFCV is closely associated with muscle fiber % CSA. RFD and jumping power are associated with the propagation of the action potentials along the muscle fibers. This link is regulated by the size and the distribution of type II, and especially type IIx muscle fibers.

Changes in sarcomere lengths of the human vastus lateralis muscle with knee flexion measured using in vivo microendoscopy

Sarcomeres are the basic contractile units of muscle, and their lengths influence muscle force-generating capacity. Despite their importance, in vivo sarcomere lengths remain unknown for many human muscles. Second harmonic generation (SHG) microendoscopy is a minimally invasive technique for imaging sarcomeres in vivo and measuring their lengths. In this study, we used SHG microendoscopy to visualize sarcomeres of the human vastus lateralis, a large knee extensor muscle important for mobility, to examine how sarcomere lengths change with knee flexion and thus affect the muscle׳s force-generating capacity. We acquired in vivo sarcomere images of several muscle fibers of the resting vastus lateralis in six healthy individuals. Mean sarcomere lengths increased (p=0.031) from 2.84±0.16μm at 50° of knee flexion to 3.17±0.13μm at 110° of knee flexion. The standard deviation of sarcomere lengths among different fibers within a muscle was 0.21±0.09μm. Our results suggest that the sarcomeres of the resting vastus lateralis at 50° of knee flexion are near optimal length. At a knee flexion angle of 110° the resting sarcomeres of vastus lateralis are longer than optimal length. These results show a smaller sarcomere length change and greater conservation of force-generating capacity with knee flexion than estimated in previous studies.

Heightened TWEAK-NF-κB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury.

Individuals with long-standing spinal cord injury (SCI) often present with extreme muscle atrophy and impaired glucose metabolism at both the skeletal muscle and whole body level. Persistent inflammation and increased levels of proinflammatory cytokines in the skeletal muscle are potential contributors to dysregulation of glucose metabolism and atrophy; however, to date no study has assessed the effects of long-standing SCI on their expression or intracellular signaling in the paralyzed muscle. In the present study, we assessed the expression of genes (TNFαR, TNFα, IL-6R, IL-6, TWEAK, TWEAK R, atrogin-1, and MuRF1) and abundance of intracellular signaling proteins (TWEAK, TWEAK R, NF-κB, and p-p65/p-50/105) that are known to mediate inflammation and atrophy in skeletal muscle. In addition, based on the effects of muscle inflammation on promotion of skeletal muscle fibrosis, we assessed the degree of fibrosis between myofibers and fascicles in both groups. For further insight into the distribution and variability of muscle fiber size, we also analyzed the frequency distribution of SCI fiber size. Resting vastus lateralis (VL) muscle biopsy samples were taken from 11 men with long-standing SCI (≈22 yr) and compared with VL samples from 11 able-bodied men of similar age. Our results demonstrated that chronic SCI muscle has heightened TNFαR and TWEAK R gene expression and NF-κB signaling (higher TWEAK R and phospho-NF-κB p65) and fibrosis, along with substantial myofiber size heterogeneity, compared with able-bodied individuals. Our data suggest that the TWEAK/TWEAK R/NF-κB signaling pathway may be an important mediator of chronic inflammation and fibrotic adaptation in SCI muscle.

Exercise efficiency is reduced by mitochondrial uncoupling in the elderly

A reduction in exercise efficiency accompanies ageing in humans. Here we evaluated the impact of changes in the contractile-coupling and mitochondrial-coupling efficiencies on the reduction in exercise efficiency in the elderly. Nine adult (mean, 38.8 years old) and 40 elderly subjects (mean, 68.8 years old) performed a cycle ergometer test to measure O2 uptake and leg power output up to the aerobic limit ( ). Reduced leg power output per unit O2 uptake was reflected in a drop in delta efficiency (εD) from 0.27 ± 0.01 (mean ± SEM) in adults to 0.22 ± 0.01 in the elderly group. Similar declines with age were apparent for both the leg power output at and the ATP generation capacity (ATPmax) determined in vivo using (31)P magnetic resonance spectroscopy. These similar declines resulted in unchanged contractile-coupling efficiency values (εC) in the adult (0.50 ± 0.05) versus the elderly group (0.58 ± 0.04) and agreed with independent measures of muscle contractile-coupling efficiency in human quadriceps (0.5). The mitochondrial-coupling efficiency calculated from the ratio of delta to contractile-coupling efficiencies in the adults (εD/εC = 0.58 ± 0.08) corresponded to values for well-coupled mitochondria (0.6); however, εD/εC was significantly lower in the elderly subjects (0.44 ± 0.03). Conversion of ATPmax per mitochondrial volume (ATPmax/Vv[mt,f]) reported in these groups into thermodynamic units confirmed this drop in mitochondrial-coupling efficiency from 0.57 ± 0.08 in adults to 0.41 ± 0.03 in elderly subjects. Thus, two independent methods revealed that reduced mitochondrial-coupling efficiency was a key part of the drop in exercise efficiency in these elderly subjects and may be an important part of the loss of exercise performance with age.

New records in aerobic power among octogenarian lifelong endurance athletes

We examined whole body aerobic capacity and myocellular markers of oxidative metabolism in lifelong endurance athletes [n = 9, 81 ± 1 yr, 68 ± 3 kg, body mass index (BMI) = 23 ± 1 kg/m(2)] and age-matched, healthy, untrained men (n = 6; 82 ± 1 y, 77 ± 5 kg, BMI = 26 ± 1 kg/m(2)). The endurance athletes were cross-country skiers, including a former Olympic champion and several national/regional champions, with a history of aerobic exercise and participation in endurance events throughout their lives. Each subject performed a maximal cycle test to assess aerobic capacity (VO(2max)). Subjects had a resting vastus lateralis muscle biopsy to assess oxidative enzymes (citrate synthase and βHAD) and molecular (mRNA) targets associated with mitochondrial biogenesis [peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (Tfam)]. The octogenarian athletes had a higher (P < 0.05) absolute (2.6 ± 0.1 vs. 1.6 ± 0.1 l/min) and relative (38 ± 1 vs. 21 ± 1 ml·kg(-1)·min(-1)) VO(2max), ventilation (79 ± 3 vs. 64 ± 7 l/min), heart rate (160 ± 5 vs. 146 ± 8 beats per minute), and final workload (182 ± 4 vs. 131 ± 14 W). Skeletal muscle oxidative enzymes were 54% (citrate synthase) and 42% (βHAD) higher (P < 0.05) in the octogenarian athletes. Likewise, basal PGC-1α and Tfam mRNA were 135% and 80% greater (P < 0.05) in the octogenarian athletes. To our knowledge, the VO(2max) of the lifelong endurance athletes is the highest recorded in humans >80 yr of age and comparable to nonendurance trained men 40 years younger. The superior cardiovascular and skeletal muscle health profile of the octogenarian athletes provides a large functional reserve above the aerobic frailty threshold and is associated with lower risk for disability and mortality.

Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease

To investigate energy metabolic and transporter characteristics in resting muscle of patients with moderate to severe chronic obstructive pulmonary disease [COPD; forced expiratory volume in 1 s (FEV(1)) = 42 +/- 6.0% (mean +/- SE)], tissue was extracted from resting vastus lateralis (VL) of 9 COPD patients and compared with that of 12 healthy control subjects (FEV(1) = 114 +/- 3.4%). Compared with controls, lower (P < 0.05) concentrations (mmol/kg dry wt) of ATP (19.6 +/- 0.65 vs. 17.8 +/- 0.69) and phosphocreatine (81.3 +/- 2.3 vs. 69.1 +/- 4.2) were observed in COPD, which occurred in the absence of differences in the total adenine nucleotide and total creatine pools. Higher concentrations were observed in COPD for several glycolytic metabolites (glucose-1-phosphate, glucose-6-phosphate, fructose-6-phosphate, pyruvate) but not lactate. Glycogen storage was not affected by the disease (289 +/- 20 vs. 269 +/- 20 mmol glucosyl units/kg dry wt). Although no difference between groups was observed for the glucose transporter GLUT1, GLUT4 was reduced by 28% in COPD. For the monocarboxylate transporters, MCT4 was 35% lower in COPD, with no differences observed for MCT1. These results indicate that in resting VL, moderate to severe COPD results in a reduction in phosphorylation potential, an apparent elevation of glycolytic flux rate, and a potential defect in glucose and lactate transport as a result of reduced levels of the principal isoforms.

Circuit Resistance Training in Chronic Heart Failure Improves Skeletal Muscle Mitochondrial ATP Production Rate—A Randomized Controlled Trial

We aimed to determine the role of skeletal muscle mitochondrial ATP production rate (MAPR) in relation to exercise tolerance after resistance training (RT) in chronic heart failure (CHF). Thirteen CHF patients (New York Heart Association functional class 2.3 +/- 0.5; Left ventricular ejection fraction 26 +/- 8%; age 70 +/- 8 years) underwent testing for peak total body oxygen consumption (VO(2peak)), and resting vastus lateralis muscle biopsy. Patients were then randomly allocated to 11 weeks of RT (n = 7), or continuance of usual care (C; n = 6), after which testing was repeated. Muscle samples were analyzed for MAPR, metabolic enzyme activity, and capillary density. VO(2peak) and MAPR in the presence of the pyruvate and malate (P+M) substrate combination, representing carbohydrate metabolism, increased in RT (P < .05) and decreased in C (P < .05), with a significant difference between groups (VO(2peak), P = .005; MAPR, P = .03). There was a strong correlation between the change in MAPR and the change in peak total body oxygen consumption (VO(2peak)) over the study (r = 0.875; P < .0001), the change in MAPR accounting for 70% of the change in VO(2peak). These findings suggest that mitochondrial ATP production is a major determinant of aerobic capacity in CHF patients and can be favorably altered by muscle strengthening exercise.

MONITORING NITRIC OXIDE-INDUCED CHANGES IN SKELETAL MUSCLE NUTRITIVE FLOW USING MICRODIALYSIS

1677 We investigated, using the microdialysis ethanol technique, the response of nutritive flow within skeletal muscle to vasoactive substances that affect nitric oxide release and/or action. Four microdialysis probes were placed in the resting vastus lateralis of the quadriceps femoris muscle group in 9 male subjects (31±6 yrs.) and perfused with a Ringer solution containing 10 mM ethanol and three successively higher doses of sodium nitroprusside (SN), acetylcholine (AC), NG-monomethyl-L-arginine (LN), norepinephrine (NE), or no additional substance (control). Data obtained with the ethanol technique are expressed as the ethanol outflow/inflow ratio (o/i ratio), which is inversely related to changes in local nutritive flow. The ethanol o/i ratio was decreased as compared to control (indicating increased nutritive flow) in response to SN and AC. The ethanol o/i ratio was increased as compared to control (indicating reduced blood flow) in response to NE and LN (Table 1: data expressed as % difference from control and are mean ± SE). These data indicate that microdialysis can be used in vivo in humans to investigate the effects of nitric oxide on the microvasculature of skeletal muscle. Furthermore, since microdialysis can also be used to monitor metabolism, this methodology allows for a unique opportunity to simultaneously investigate the effects of nitric oxide on skeletal muscle nutritive flow and metabolism.TableThis study was supported by a Faculty Research Grant from East Carolina University