The 3D muscle morphology and intramuscular innervation of the digital bellies of flexor digitorum profundus: Clinical implications for botulinum toxin injection sites.

Spasticity of flexor digitorum profundus is frequently managed with botulinum toxin injections. Knowledge of the 3D morphology and intramuscular innervation of the digital bellies of flexor digitorum profundus is necessary to optimize the injections. The purpose of this study was to digitize and model in 3D the contractile and connective tissue elements of flexor digitorum profundus to determine muscle morphology, model and map the intramuscular innervation and propose sites for botulinum toxin injection. Fiber bundles (FBs)/aponeuroses and intramuscular nerve branches were dissected and digitized in 12 formalin embalmed cadaveric specimens. Cartesian coordinate data were reconstructed into 3D models as in situ to visualize and compare the muscle morphology and intramuscular innervation patterns of the bellies of flexor digitorum profundus. The 3rd, 4th and 5th digital bellies were superficial to the 2nd digital belly and located adjacent to each other in all specimens. Each digital belly had distinct intramuscular innervation patterns. The 2nd digital belly received intramuscular branches from the anterior interosseus nerve (AIN). The superior half of the 3rd digital belly was innervated intramuscularly by the ulnar nerve (n = 4) or by both the anterior interosseus and ulnar nerves (n = 1). The inferior half of the belly received dual innervation from the anterior interosseus and ulnar nerves in 2 specimens, or exclusively from the AIN (n = 2) or the ulnar nerve (n = 1). The 4th digital belly was innervated by intramuscular branches of the ulnar nerve. One main branch, after coursing through the 4th digital belly, entered the lateral aspect of the 5th digital belly and arborized intramuscularly. The morphology of the FBs, aponeuroses and intramuscular innervation of the digital bellies of FDP were mapped and modelled volumetrically in 3D as in situ. Previous studies were not volumetric nor identified the course of the intramuscular nerve branches within each digital belly. Based on the intramuscular innervation of each of the digital bellies, one possible optimized botulinum toxin injection location was proposed. This injection location, at the junction of the superior and middle thirds of the forearm, would be located in dense nerve terminal zones of the anterior interosseus and ulnar nerves. Future anatomical and clinical investigations are necessary to evaluate the efficacy of these anatomical findings in the management of spasticity.

The Effects of Power Training Frequency on Muscle Power and Functional Performance in Older Women: A Randomized Controlled Trial.

ABSTRACT: Katsoulis, K and Amara, CE. The effects of power training frequency on muscle power and functional performance in older women: a randomized controlled trial. J Strength Cond Res 37(11): 2289-2297, 2023-Low-intensity power training (PT) has emerged as an effective method for improving muscle power and functional performance in older adults. However, effects of low training frequencies are less understood and could expand the repertoire of exercise prescription, particularly in older women who experience greater functional disability with age compared with men. This study investigated the impact of frequency of low-intensity (40% of 1 repetition maximum, 1RM) PT on lower-body power and functional performance in healthy older women. Women (74 ± 4 years) were randomized to 12 weeks of PT of 1 (PT1, n = 14), 2 (PT2, n = 17), or 3 (PT3, n = 17) d·wk -1 or wait control (CON, n = 15). Measures included leg press 1RM, knee extension power (KEP), and functional performance (stair climb power, stair climb time, 30-second chair stands, 400-m walk, Short Physical Performance Battery). There were no differences between the frequency of training in changes in leg press 1RM, KEP, or functional performance after 12 weeks. Pre-post data for individual training groups revealed that leg press 1RM improved in all PT groups (20-33%, p < 0.05). Furthermore, KEP improved in PT2 and PT3 by 10 and 12%, respectively, and all PT groups improved in the 30-second chair stands and Short Physical Performance Battery (6-22%), whereas PT1 and PT3 improved in the 400-m walk and PT2 improved in stair climb power and stair climb time after training (4-7%, p < 0.05). One to 3 weekly low-intensity PT sessions can improve functional performance, although improvements in both functional performance and power might require 2 or 3 sessions per week in older healthy women.

The Effects of High- Versus Low-Intensity Power Training on Muscle Power Outcomes in Healthy, Older Adults: A Systematic Review.

Power training (PT) improves muscle power in older adults; however, intensity recommendations are less clear. A narrative approach was used to compare high- versus low-intensity PT on muscle power (and function) in healthy, older adults. Searches were performed using Medline, Embase, CINAHL, SPORTDiscus, AgeLine, and Scopus. Interventions in which older subjects (60+ years) were instructed to perform the concentric phase "as fast as possible" were included. After searches were performed, a third category of PT (moderate intensity) was included. Evidence from 27 studies (32 PT groups) showed changes in muscle power that averaged 26.8%, 33.4%, and 21.5% for high-, moderate-, and low-intensity PT, respectively, with greater changes with longer training duration and in mildly mobility-limited older adults. Function improved similarly across categories. In conclusion, both low- and high-intensity PT led to clinically significant changes in power and are viable options for improving power and function in older adults.

Reliability of Lower Extremity Muscle Power and Functional Performance in Healthy, Older Women.

Evaluation of the long-term reliability of muscle power and functional performance tests in older, healthy adults is warranted since determining whether performance is consistent over longer durations is more relevant for intervention studies. Objective. To assess the long-term test-retest reliability of measures of muscle power and lower body functional performance in healthy, nonexercising, older women. Methods. Data were derived from a nonexercising control group (n = 18; age = 73.3 (3.4) years; height = 159.6 (7.7) cm; body mass = 69.5 (12.7) kg; BMI = 27.3 (4.8)) of a randomized controlled trial of muscle power training in older women. Participants underwent lower extremity muscle power (Biodex) and functional testing (Short Physical Performance Battery, gait speed, 30-second chair stands, stair climbing, and 400-meter walk) at week 0 (baseline), 9, and 15. Results. For the upper leg, intraclass correlation coefficients (ICCs) were very high for knee extension power (0.90-0.97) and high to very high for knee flexion power (0.83-0.96). For lower-leg power, ICCs were high to very high for plantar flexion and dorsiflexion (0.83-0.96). ICCs for functional performance were moderate to very high (0.64-0.93). Coefficient of variation of the typical error (CVTE) was <10.5% for knee extension/flexion power, 9.9-20.0% for plantar flexion/dorsiflexion power, and 1.9-14.9% for functional performance. Knee extension power and stair climb power demonstrated the highest reliability for muscle power and function, respectively. Mean values did not change over time, with the exception of the chair stands (p < 0.05); however, these changes were not considered clinically meaningful. Conclusions. The current study provides evidence supporting the long-term reliability of performance assessments of muscle power and lower body functional capacity over a period of up to 15 weeks in healthy, older women.

Mitochondrial function in vivo: spectroscopy provides window on cellular energetics.

Mitochondria integrate the key metabolic fluxes in the cell. This role places this organelle at the center of cellular energetics and, hence, mitochondrial dysfunction underlies a growing number of human disorders and age-related degenerative diseases. Here we present novel analytical and technical methods for evaluating mitochondrial metabolism and (dys)function in human muscle in vivo. Three innovations involving advances in optical spectroscopy (OS) and magnetic resonance spectroscopy (MRS) permit quantifying key compounds in energy metabolism to yield mitochondrial oxidation and phosphorylation fluxes. The first of these uses analytical methods applied to optical spectra to measure hemoglobin (Hb) and myoglobin (Mb) oxygenation states and relative contents ([Hb]/[Mb]) to determine mitochondrial respiration (O2 uptake) in vivo. The second uses MRS methods to quantify key high-energy compounds (creatine phosphate, PCr, and adenosine triphosphate, ATP) to determine mitochondrial phosphorylation (ATP flux) in vivo. The third involves a functional test that combines these spectroscopic approaches to determine mitochondrial energy coupling (ATP/O2), phosphorylation capacity (ATP(max)) and oxidative capacity (O2max) of muscle. These new developments in optical and MR tools allow us to determine the function and capacity of mitochondria noninvasively in order to identify specific defects in vivo that are associated with disease in human and animal muscle. The clinical implication of this unique diagnostic probe is the insight into the nature and extent of dysfunction in metabolic and degenerative disorders, as well as the ability to follow the impact of interventions designed to reverse these disorders.

Wavelength shift analysis: a simple method to determine the contribution of hemoglobin and myoglobin to in vivo optical spectra.

The ability to quantify the contributions of hemoglobin (Hb) and myoglobin (Mb) to in vivo optical spectra has many applications for clinical and research use such as noninvasive measurement of local tissue O(2) uptake rates and regional blood content. Recent work has demonstrated an approach to independently measure oxygen saturations of Hb and Mb in optical spectra collected in vivo. However, the utility of this approach is limited without information on tissue concentrations of these species. Here we describe a strategy to quantify the contributions of Hb and Mb to in vivo optical spectra. We have found that the peak position of the deoxy-heme peak around 760 nm in the optical spectra of the deoxygenated tissue is a linear function of the relative contributions of Hb and Mb to the optical spectra. Therefore, analysis of this peak position, hereafter referred to as wavelength shift analysis, reveals the relative concentration of Hb to Mb in solutions and intact tissue. Biochemical analysis of muscle homogenates confirmed that the wavelength shift of the combined Hb/Mb peak in in vivo spectra reflects the ratio of concentrations (Hb/Mb) in muscle. The importance of quantifying the Hb contribution is illustrated by our data demonstrating that Hb accounts for approximately 80% of the optical signal in mouse skeletal muscle but only approximately 20% in human skeletal muscle. This advance will facilitate comparison of the metabolic properties between individual muscles and provides a fully noninvasive approach to measuring local respiration that can be adapted for clinical use.

Mild eccentric exercise increases Hsp72 content in skeletal muscles from adult and late middle-aged rats.

The loss of muscle mass with age or sarcopenia contributes to increased morbidity and mortality. Thus, preventing muscle loss with age is important for maintaining health. Hsp72, the inducible member of the Hsp70 family, is known to provide protection to skeletal muscle and can be increased by exercise. However, ability to increase Hsp72 by exercise is intensity-dependent and appears to diminish with advanced age. Thus, other exercise modalities capable of increasing HSP content and potentially preventing the age related loss of muscle need to be explored. The purpose of this study was to determine if the stress from one bout of mild eccentric exercise was sufficient to elicit an increase in Hsp72 content in the vastus intermedius (VI) and white gastrocnemius (WG) muscles, and if the Hsp72 response differed between adult and late middle-aged rats. To do this, 30 adult (6 months) and late middle-aged (24 months) F344BN rats were randomly divided into three groups (n = 6/group): control (C), level exercise (16 m x min(-1)) and eccentric exercise (16 m x min(-1), 16 degree decline). Exercised animals were sacrificed immediately post-exercise or after 48 hours. Hematoxylin and Eosin staining was used to assess muscle damage, while Western Blotting was used to measure muscle Hsp72 content. A nested ANOVA with Tukey post hoc analysis was performed to determine significant difference (p < 0.05) between groups. Hsp72 content was increased in the VI for both adult and late middle-aged rats 48 hours after eccentric exercise when compared to level and control groups but no differences between age groups was observed. Hsp72 was not detected in the WG following any type of exercise. In conclusion, mild eccentric exercise can increase Hsp72 content in the rat VI muscle and this response is maintained into late middle-age.

Higher mitochondrial respiration and uncoupling with reduced electron transport chain content in vivo in muscle of sedentary versus active subjects.

OBJECTIVE: This study investigated the disparity between muscle metabolic rate and mitochondrial metabolism in human muscle of sedentary vs. active individuals. RESEARCH DESIGN AND METHODS: Chronic activity level was characterized by a physical activity questionnaire and a triaxial accelerometer as well as a maximal oxygen uptake test. The ATP and O(2) fluxes and mitochondrial coupling (ATP/O(2) or P/O) in resting muscle as well as mitochondrial capacity (ATP(max)) were determined in vivo in human vastus lateralis muscle using magnetic resonance and optical spectroscopy on 24 sedentary and seven active subjects. Muscle biopsies were analyzed for electron transport chain content (using complex III as a representative marker) and mitochondrial proteins associated with antioxidant protection. RESULTS: Sedentary muscle had lower electron transport chain complex content (65% of the active group) in proportion to the reduction in ATP(max) (0.69 ± 0.07 vs. 1.07 ± 0.06 mM sec(-1)) as compared with active subjects. This lower ATP(max) paired with an unchanged O(2) flux in resting muscle between groups resulted in a doubling of O(2) flux per ATP(max) (3.3 ± 0.3 vs. 1.7 ± 0.2 µM O(2) per mM ATP) that reflected mitochondrial uncoupling (P/O = 1.41 ± 0.1 vs. 2.1 ± 0.3) and greater UCP3/complex III (6.0 ± 0.7 vs. 3.8 ± 0.3) in sedentary vs. active subjects. CONCLUSION: A smaller mitochondrial pool serving the same O(2) flux resulted in elevated mitochondrial respiration in sedentary muscle. In addition, uncoupling contributed to this higher mitochondrial respiration. This finding resolves the paradox of stable muscle metabolism but greater mitochondrial respiration in muscle of inactive vs. active subjects.

Serum leptin is not correlated with body fat in severe food restriction.

Leptin is an adipose-derived hormone with established roles in energy balance that can impact the response to refeeding after malnutrition. Although the amount of circulating leptin has traditionally been associated with the amount of adipose tissue, controversy exists as to whether this relationship is constant in both humans and animals and over a wide range of body composition. Our objective was to evaluate whether the leptin - body fat ratio is constant in the range of healthy to low body mass in female Wistar rats. Eight ad libitum fed (C) and eight food-restricted (FR) rats were compared over a period of four weeks. FR rats attained the target 75% of baseline body mass after the first two weeks, which was maintained for the remaining two weeks. Serum leptin and IGF-1 (ELISA) and body composition (DXA) were measured at baseline (t(0)) and once weekly for the remainder of the study (t(1)-t(4)). The leptin - body fat ratio was reduced during the two-week period of weight loss (t(0) = 0.036 ± 0.016 (ng·mL(-1))·g(-1) vs. t(1) = 0.010 ± 0.004 (ng·mL(-1))·g(-1) and t(2) = 0.015 ± 0.007 (ng·mL(-1))·g(-1), p < 0.05). Leptin concentration plateaued at its nadir (~0.24 (ng·mL(-1))·g(-1)) at fat mass < 22 g. IGF-1 was correlated with lean mass (r = 0.45, p < 0.05) and fat mass (r = 0.58, p < 0.05), regardless of body mass. We concluded that the leptin - body fat ratio was reduced early in food restriction and the correlation between these two variables was absent at low body fat.

Synthetic signal injection using inductive coupling.

Conversion of MR signals into units of metabolite concentration requires a very high level of diligence to account for the numerous parameters and transformations that affect the proportionality between the quantity of excited nuclei in the acquisition volume and the integrated area of the corresponding peak in the spectrum. We describe a method that eases this burden with respect to the transformations that occur during and following data acquisition. The conceptual approach is similar to the ERETIC method, which uses a pre-calibrated, artificial reference signal as a calibration factor to accomplish the conversion. The distinguishing feature of our method is that the artificial signal is introduced strictly via induction, rather than radiation. We tested a prototype probe that includes a second RF coil rigidly positioned close to the receive coil so that there was constant mutual inductance between them. The artificial signal was transmitted through the second RF coil and acquired by the receive coil in parallel with the real signal. Our results demonstrate that the calibration factor is immune to changes in sample resistance. This is a key advantage because it removes the cumbersome requirement that coil loading conditions be the same for the calibration sample as for experimental samples. The method should be adaptable to human studies and could allow more practical and accurate quantification of metabolite content.

Mitochondrial function, fibre types and ageing: new insights from human muscle in vivo.

Mitochondrial changes are at the centre of a wide range of maladies, including diabetes, neurodegeneration and ageing-related dysfunctions. Here we describe innovative optical and magnetic resonance spectroscopic methods that non-invasively measure key mitochondrial fluxes, ATP synthesis and O(2) uptake, to permit the determination of mitochondrial coupling efficiency in vivo (P/O: half the ratio of ATP flux to O(2) uptake). Three new insights result. First, mitochondrial coupling can be measured in vivo with the rigor of a biochemical determination and provides a gold standard to define well-coupled mitochondria (P/O approximately 2.5). Second, mitochondrial coupling differs substantially among muscles in healthy adults, from values reflective of well-coupled oxidative phosphorylation in a hand muscle (P/O = 2.7) to mild uncoupling in a leg muscle (P/O = 2.0). Third, these coupling differences have an important impact on cell ageing. We found substantial uncoupling and loss of cellular [ATP] in a hand muscle indicative of mitochondrial dysfunction with age. In contrast, stable mitochondrial function was found in a leg muscle, which supports the notion that mild uncoupling is protective against mitochondrial damage with age. Thus, greater mitochondrial dysfunction is evident in muscles with higher type II muscle fibre content, which may be at the root of the preferential loss of type II fibres found in the elderly. Our results demonstrate that mitochondrial function and the tempo of ageing varies among human muscles in the same individual. These technical advances, in combination with the range of mitochondrial properties available in human muscles, provide an ideal system for studying mitochondrial function in normal tissue and the link between mitochondrial defects and cell pathology in disease.

Mitochondrial dysfunction: impact on exercise performance and cellular aging.

Innovative noninvasive methods open a new window on the cell in vivo. This window reveals that the tempo of mitochondrial dysfunction with age varies among muscles and in proportion to Type II muscle fiber content. Exercise training can reverse age-related dysfunction, thereby providing an intervention to slow the pace of aging and disability in the elderly.

Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo.

Faster aging is predicted in more active tissues and animals because of greater reactive oxygen species generation. Yet age-related cell loss is greater in less active cell types, such as type II muscle fibers. Mitochondrial uncoupling has been proposed as a mechanism that reduces reactive oxygen species production and could account for this paradox between longevity and activity. We distinguished these hypotheses by using innovative optical and magnetic resonance spectroscopic methods applied to noninvasively measured ATP synthesis and O(2) uptake in vivo in human muscle. Here we show that mitochondrial function is unchanged with age in mildly uncoupled tibialis anterior muscle (75% type I) despite a high respiratory rate in adults. In contrast, substantial uncoupling and loss of cellular [ATP] indicative of mitochondrial dysfunction with age was found in the lower respiring and well coupled first dorsal interosseus (43-50% type II) of the same subjects. These results reject respiration rate as the sole factor impacting the tempo of cellular aging. Instead, they support mild uncoupling as a mechanism protecting mitochondrial function and contributing to the paradoxical longevity of the most active muscle fibers.

Allometric scaling of strength in an independently living population age 55-86 years.

Most physiological functions vary allometrically with body size; however, few investigators have examined the relationship between strength and body size with allometric scaling. Thus, we hypothesized that allometric analysis would reveal that both the amount and quality of muscle are significant determinants of strength in the elderly. Allometric analyses were used to determine the influence of limb cross-sectional area (CSA), physical activity, demispan (distance between index-middle finger web and the sternal notch), leg length, and sex on grip and plantar flexor strength in men (n = 188) and women (n = 205) age 55-86 years. Physical activity was measured using a self-reporting questionnaire (Taylor et al. [1978] J Chron Dis 31:741-755). Forearm and leg CSA was estimated from anthropometry. There was an age-related decline in grip strength, independent of forearm CSA, demispan, and sex, equal to approximately 12% per decade, whereas plantar flexor strength adjusted for leg CSA, physical activity, and sex was reduced at a rate of approximately 15% per decade. The allometric models explained 71.4% (r = 0.845) and 38.8% (r = 0.623) of the variance in grip and plantar flexor strength, respectively. Model parameters were identified using multiple linear regression (P < 0.05). Thus, grip strength = forearm CSA(0.435). demispan(0.161). exp(3.905 - 0.012 age + 0.413 sex) and plantar flexor strength = leg CSA(0.223). physical activity (0.115). exp(5.867 - 0.015 age + 0.366 sex). These findings indicate that age-related reductions in muscle CSA do not fully account for strength declines with age. Physical activity is also important and partially explains these reductions.