Resistance training for the older adult: Manipulating training variables to enhance muscle strength

Resistance training has been shown to reliably and substantially enhance muscle function in older adults and these improvements can be accompanied by improved functional performance. Training variables should be manipulated to enhance muscle strength and minimize injury risks in this population.

Engineering Highly-functional, Self-regenerative Skeletal Muscle Tissues with Enhanced Vascularization and Survival in Vivo

Tissue engineering of biomimetic skeletal muscle may lead to development of new therapies for myogenic repair and generation of improved in vitro models for studies of muscle function, regeneration, and disease. For the optimal therapeutic and in vitro results, engineered muscle should recreate the force-generating and regenerative capacities of native muscle, enabled respectively by its two main cellular constituents, the mature myofibers and satellite cells (SCs). Still, after 20 years of research, engineered muscle tissues fall short of mimicking contractile function and self-repair capacity of native skeletal muscle. To overcome this limitation, we set the thesis goals to: 1) generate a highly functional, self-regenerative engineered skeletal muscle and 2) explore mechanisms governing its formation and regeneration in vitro and survival and vascularization in vivo.

By studying myogenic progenitors isolated from neonatal rats, we first discovered advantages of using an adherent cell fraction for engineering of skeletal muscles with robust structure and function and the formation of a SC pool. Specifically, when synergized with dynamic culture conditions, the use of adherent cells yielded muscle constructs capable of replicating the contractile output of native neonatal muscle, generating >40 mN/mm2 of specific force. Moreover, tissue structure and cellular heterogeneity of engineered muscle constructs closely resembled those of native muscle, consisting of aligned, striated myofibers embedded in a matrix of basal lamina proteins and SCs that resided in native-like niches. Importantly, we identified rapid formation of myofibers early during engineered muscle culture as a critical condition leading to SC homing and conversion to a quiescent, non-proliferative state. The SCs retained natural regenerative capacity and activated, proliferated, and differentiated to rebuild damaged myofibers and recover contractile function within 10 days after the muscle was injured by cardiotoxin (CTX). The resulting regenerative response was directly dependent on the abundance of SCs in the engineered muscle that we varied by expanding starting cell population under different levels of basic fibroblast growth factor (bFGF), an inhibitor of myogenic differentiation. Using a dorsal skinfold window chamber model in nude mice, we further demonstrated that within 2 weeks after implantation, initially avascular engineered muscle underwent robust vascularization and perfusion and exhibited improved structure and contractile function beyond what was achievable in vitro.

To enhance translational value of our approach, we transitioned to use of adult rat myogenic cells, but found that despite similar function to that of neonatal constructs, adult-derived muscle lacked regenerative capacity. Using a novel platform for live monitoring of calcium transients during construct culture, we rapidly screened for potential enhancers of regeneration to establish that many known pro-regenerative soluble factors were ineffective in stimulating in vitro engineered muscle recovery from CTX injury. This led us to introduce bone marrow-derived macrophages (BMDMs), an established non-myogenic contributor to muscle repair, to the adult-derived constructs and to demonstrate remarkable recovery of force generation (>80%) and muscle mass (>70%) following CTX injury. Mechanistically, while similar patterns of early SC activation and proliferation upon injury were observed in engineered muscles with and without BMDMs, a significant decrease in injury-induced apoptosis occurred only in the presence of BMDMs. The importance of preventing apoptosis was further demonstrated by showing that application of caspase inhibitor (Q-VD-OPh) yielded myofiber regrowth and functional recovery post-injury. Gene expression analysis suggested muscle-secreted tumor necrosis factor-α (TNFα) as a potential inducer of apoptosis as common for muscle degeneration in diseases and aging in vivo. Finally, we showed that BMDM incorporation in engineered muscle enhanced its growth, angiogenesis, and function following implantation in the dorsal window chambers in nude mice.

In summary, this thesis describes novel strategies to engineer highly contractile and regenerative skeletal muscle tissues starting from neonatal or adult rat myogenic cells. We find that age-dependent differences of myogenic cells distinctly affect the self-repair capacity but not contractile function of engineered muscle. Adult, but not neonatal, myogenic progenitors appear to require co-culture with other cells, such as bone marrow-derived macrophages, to allow robust muscle regeneration in vitro and rapid vascularization in vivo. Regarding the established roles of immune system cells in the repair of various muscle and non-muscle tissues, we expect that our work will stimulate the future applications of immune cells as pro-regenerative or anti-inflammatory constituents of engineered tissue grafts. Furthermore, we expect that rodent studies in this thesis will inspire successful engineering of biomimetic human muscle tissues for use in regenerative therapy and drug discovery applications.

The role of intracellular calcium perturbations in muscle damage and dysfunction in mouse models of muscular dystrophy

Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused by mutations in the dystrophin gene. DMD is clinically characterized by severe, progressive and irreversible loss of muscle function, in which most patients lose the ability to walk by their early teens and die by their early 20’s. Impaired intracellular calcium (Ca2+) regulation and activation of cell degradation pathways have been proposed as key contributors to DMD disease progression. This dissertation research consists of three studies investigating the role of intracellular Ca2+ in skeletal muscle dysfunction in different mouse models of DMD. Study one evaluated the role of Ca2+-activated enzymes (proteases) that activate protein degradation in excitation-contraction (E-C) coupling failure following repeated contractions in mdx and dystrophin-utrophin null (mdx/utr-/-) mice. Single muscle fibers from mdx/utr-/- mice had greater E-C coupling failure following repeated contractions compared to fibers from mdx mice. Moreover, protease inhibition during these contractions was sufficient to attenuate E-C coupling failure in muscle fibers from both mdx and mdx/utr-/- mice. Study two evaluated the effects of overexpressing the Ca2+ buffering protein sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1 (SERCA1) in skeletal muscles from mdx and mdx/utr-/- mice. Overall, SERCA1 overexpression decreased muscle damage and protected the muscle from contraction-induced injury in mdx and mdx/utr-/- mice. In study three, the cellular mechanisms underlying the beneficial effects of SERCA1 overexpression in mdx and mdx/utr-/- mice were investigated. SERCA1 overexpression attenuated calpain activation in mdx muscle only, while partially attenuating the degradation of the calpain target desmin in mdx/utr-/- mice. Additionally, SERCA1 overexpression decreased the SERCA-inhibitory protein sarcolipin in mdx muscle but did not alter levels of Ca2+ regulatory proteins (parvalbumin and calsequestrin) in either dystrophic model. Lastly, SERCA1 overexpression blunted the increase in endoplasmic reticulum stress markers Grp78/BiP in mdx mice and C/EBP homologous protein (CHOP) in mdx and mdx/utr-/- mice. Overall, findings from the studies presented in this dissertation provide new insight into the role of Ca2+ in muscle dysfunction and damage in different dystrophic mouse models. Further, these findings support the overall strategy for improving intracellular Ca2+ control for the development of novel therapies for DMD.

Muscle fatigue resistance: comparison of Martin vigorimeter and Jamar dynamometer in community-dwelling people

Background: For the diagnosis of frailty exhaustion is a criteria currently measured by self-reported questionnaires, which are subjective and dependent on individual perception. The FR test has been developed as a bed side objective evaluation of muscle fatigue. The test was validated for the VM. However, the JD is frequently used to measure the grip strength. So the comparison of these devices is required to understand if FR is similar when measured with both devices. Methods: Fifty-four (29 female and 25 male; mean age: 39.98 ± 18.09) community-dwelling people were tested for muscle function. The Fatigue resistance (FR), which is the time during that grip strength drops to 50% of its maximum, was recorded with each device and simultaneous sEMG of the forearm muscles was obtained. The (co-)activation of agonist and antagonist muscles was calculated and compared with the differences between the performances with each device (controlling for gender and age). Results: FR was significantly better when measured with VM compared to JD. At all phases of the FR-test the antagonist muscle co-activation was significantly higher for VM compared to JD. In contrast, the agonist muscle activation level was significantly higher in JD compared to VM. When performing the FR-test with VM, both the agonist muscle activation and antagonist muscle co-activation decreased significantly (p<0.05). Whereas when using the JD, only a significant decrease in the antagonist muscle co-activation was observed. The difference in antagonist muscle activation between VM and JD was significantly related to the difference in FR between both devices. Conclusion: The results suggest that the FR-test when using the VM induces a more prominent muscle exhaustion than when using the JD, which makes the VM more suitable for measuring muscle fatigue resistance. However, these findings must be confirmed in a larger study population.

Diaphragm muscle adaptation to sustained hypoxia: lessons from animal models with relevance to high altitude and chronic respiratory diseases

The diaphragm is the primary inspiratory pump muscle of breathing. Notwithstanding its critical role in pulmonary ventilation, the diaphragm like other striated muscles is malleable in response to physiological and pathophysiological stressors, with potential implications for the maintenance of respiratory homeostasis. This review considers hypoxic adaptation of the diaphragm muscle, with a focus on functional, structural, and metabolic remodeling relevant to conditions such as high altitude and chronic respiratory disease. On the basis of emerging data in animal models, we posit that hypoxia is a significant driver of respiratory muscle plasticity, with evidence suggestive of both compensatory and deleterious adaptations in conditions of sustained exposure to low oxygen. Cellular strategies driving diaphragm remodeling during exposure to sustained hypoxia appear to confer hypoxic tolerance at the expense of peak force-generating capacity, a key functional parameter that correlates with patient morbidity and mortality. Changes include, but are not limited to: redox-dependent activation of hypoxia-inducible factor (HIF) and MAP kinases; time-dependent carbonylation of key metabolic and functional proteins; decreased mitochondrial respiration; activation of atrophic signaling and increased proteolysis; and altered functional performance. Diaphragm muscle weakness may be a signature effect of sustained hypoxic exposure. We discuss the putative role of reactive oxygen species as mediators of both advantageous and disadvantageous adaptations of diaphragm muscle to sustained hypoxia, and the role of antioxidants in mitigating adverse effects of chronic hypoxic stress on respiratory muscle function.

Early life exposure to chronic intermittent hypoxia primes increased susceptibility to hypoxia-induced weakness in rat sternohyoid muscle during adulthood

Intermittent hypoxia is a feature of apnea of prematurity (AOP), chronic lung disease, and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH) during postnatal development (pCIH) causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 h of delivery, pups and their respective dams were exposed to CIH: 90 s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 h per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH), where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm) weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

Changes in inflammatory mediators following eccentric exercise of the elbow flexors

The aims of this study were to examine the plasma concentrations of inflammatory mediators including cytokines induced by a single bout of eccentric exercise and again 4 weeks later by a second bout of eccentric exercise of the same muscle group. Ten untrained male subjects performed two bouts of the eccentric exercise involving the elbow flexors (6 sets of 5 repetitions) separated by four weeks. Changes in muscle soreness, swelling, and function following exercise were compared between the bouts. Blood was sampled before, immediately after, 1 h, 3 h, 6 h, 24 h (1 d), 48 h (2 d), 72 h (3 d), 96 h (4 d) following exercise bout to measure plasma creatine kinase (CK) activity, plasma concentrations of myoglobin (Mb), interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra), IL-4, IL-6, IL-8, IL-10, IL-12p40, tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), myeloperoxidase (MPO), prostaglandin E2 (PGE2), heat shock protein (HSP) 60 and 70. After the first bout, muscle soreness increased significantly, and there was also significant increase in upper arm circumference; muscle function decreased and plasma CK activity and Mb concentration increased significantly. These changes were significantly smaller after the second bout compared to the first bout, indicating muscle adaptation to the repeated bouts of the eccentric exercise. Despite the evidence of greater muscle damage after the first bout, the changes in cytokines and other inflammatory mediators were quite minor, and considerably smaller than that following endurance exercise. These results suggest that eccentric exercise-induced muscle damage is not associated with the significant release of cytokines into the systemic circulation. After the first bout, plasma G-CSF concentration showed a small but significant increase, whereas TNF-alpha and IL-8 showed significant decreases compared to the pre-exercise values. After the second bout, there was a significant increase in IL-10, and a significant decrease in IL-8. In conclusion, although there was evidence of severe muscle damage after the eccentric exercise, this muscle damage was not accompanied by any large changes in plasma cytokine concentrations. The minor changes in systemic cytokine concentration found in this study might reflect more rapid clearance from the circulation, or a lack of any significant metabolic or oxidative demands during this particular mode of exercise. In relation to the adaptation to the muscle damage, the anti-inflammatory cytokine IL-10 might work as one of the underlying mechanisms of action.

Comparison between electrically-evoked and voluntary wrist movements on sensorimotor and prefrontal cortical activation : A multi-channel time domain fNIRS study

Neuromuscular electrical stimulation (NMES) has been consistently demonstrated to improve skeletal muscle function in neurological populations with movement disorders, such as poststroke and incomplete spinal cord injury (Vanderthommen and Duchateau, 2007). Recent research has documented that rapid, supraspinal central nervous system reorganisation/neuroplastic mechanisms are also implicated during NMES (Chipchase et al., 2011). Functional neuroimaging studies have shown NMES to activate a network of sub-cortical and cortical brain regions, including the sensorimotor (SMC) and prefrontal (PFC) cortex (Blickenstorfer et al., 2009; Han et al., 2003; Muthalib et al., 2012). A relationship between increase in SMC activation with increasing NMES current intensity up to motor threshold has been previously reported using functional MRI (Smith et al., 2003). However, since clinical neurorehabilitation programmes commonly utilise NMES current intensities above the motor threshold and up to the maximum tolerated current intensity (MTI), limited research has determined the cortical correlates of increasing NMES current intensity at or above MTI (Muthalib et al., 2012). In our previous study (Muthalib et al., 2012), we assessed contralateral PFC activation using 1-channel functional near infrared spectroscopy (fNIRS) during NMES of the elbow flexors by increasing current intensity from motor threshold to greater than MTI and showed a linear relationship between NMES current intensity and the level of PFC activation. However, the relationship between NMES current intensity and activation of the motor cortical network, including SMC and PFC, has not been clarified. Moreover, it is of scientific and clinical relevance to know how NMES affects the central nervous system, especially in comparison to voluntary (VOL) muscle activation. Therefore, the aim of this study was to utilise multi-channel time domain fNIRS to compare SMC and PFC activation between VOL and NMESevoked wrist extension movements.

Antioxidants in Athlete's Basic Nutrition: Considerations towards a Guideline for the Intake of Vitamin C and Vitamin E

Antioxidants in acute physical exercise and exercise training remain a hot topic in sport nutrition, exercise physiology and biology, in general (Jackson, 2008; Margaritis and Rousseau, 2008; Gomez-Cabrera et al., 2012; Nikolaidis et al., 2012). During the past few decades, antioxidants have received attention predominantly as a nutritional strategy for preventing or minimising detrimental effects of reactive oxygen and nitrogen species (RONS), which are generated during and after strenuous exercise (Jackson, 2008, 2009; Powers and Jackson, 2008). Antioxidant supplementation has become a common practice among athletes as a means to (theoretically) reduce oxidative stress, promote recovery and enhance performance (Peternelj and Coombes, 2011). However, until now, requirements of antioxidant micronutrients and antioxidant compounds for athletes training for and competing in different sport events, including marathon running, triathlon races or team sport events involving repeated sprinting, have not been determined sufficiently (Williams et al., 2006; Margaritis and Rousseau, 2008). Crucially, evidence has been emerging that higher dosages of antioxidants may not necessarily be beneficial in this context, but can also elicit detrimental effects by interfering with performance-enhancing (Gomez-Cabrera et al., 2008) and health-promoting training adaptations (Ristow et al., 2009). As originally postulated in a pioneering study on exercise-induced production of RONS by Davies et al. (1982) in the early 1980s, evidence has been increasing in recent years that RONS are not only damaging agents, but also act as signalling molecules for regulating muscle function (Reid, 2001; Jackson, 2008) and for initiating adaptive responses to exercise (Jackson, 2009; Powers et al., 2010). The recognition that antioxidants could, vice versa, interact with the signalling pathways underlying the responses to acute (and repeated) bouts of exercise has contributed important novel aspects to the continued discussion on antioxidant requirements for athletes. In view of the recent advances in this field, it is the aim of this report to examine the current knowledge of antioxidants, in particular of vitamins C and E, in the basic nutrition of athletes. While overviews on related topics including basic mechanisms of exercise-induced oxidative stress, redox biology, antioxidant defence systems and a summary of studies on antioxidant supplementation during exercise training are provided, this does not mean that this report is comprehensive. Several issues of the expanding and multidisciplinary field of antioxidants and exercise are covered elsewhere in this book and/or in the literature. Exemplarily, the reader is referred to reviews on oxidative stress (Konig et al., 2001; Vollaard et al., 2005; Knez et al., 2006; Powers and Jackson, 2008; Nikolaidis et al., 2012), redox-sensitive signalling and muscle function (Reid, 2001; Vollaard et al., 2005; Jackson, 2008; Ji, 2008; Powers and Jackson, 2008; Powers et al., 2010; Radak et al., 2013) and antioxidant supplementation (Williams et al., 2006; Peake et al., 2007; Peternelj and Coombes, 2011) in the context with exercise. Within the scope of the report, we rather aim to address the question regarding requirements of antioxidants, specifically vitamins C and E, during exercise training, draw conclusions and provide practical implications from the recent research.

Electromyography and sonomyography analysis of the tibialis anterior: a cross sectional study

Background Foot dorsiflexion plays an essential role in both controlling balance and human gait. Electromyography (EMG) and sonomyography (SMG) can provide information on several aspects of muscle function. The aim was to establish the relationship between the EMG and SMG variables during isotonic contractions of foot dorsiflexors. Methods Twenty-seven healthy young adults performed the foot dorsiflexion test on a device designed ad hoc. EMG variables were maximum peak and area under the curve. Muscular architecture variables were muscle thickness and pennation angle. Descriptive statistical analysis, inferential analysis and a multivariate linear regression model were carried out. The confidence level was established with a statistically significant p-value of less than 0.05. Results The correlation between EMG variables and SMG variables was r = 0.462 (p < 0.05). The linear regression model to the dependent variable “peak normalized tibialis anterior (TA)” from the independent variables “pennation angle and thickness”, was significant (p = 0.002) with an explained variance of R2 = 0.693 and SEE = 0.16. Conclusions There is a significant relationship and degree of contribution between EMG and SMG variables during isotonic contractions of the TA muscle. Our results suggest that EMG and SMG can be feasible tools for monitoring and assessment of foot dorsiflexors. TA muscle parameterization and assessment is relevant in order to know that increased strength accelerates the recovery of lower limb injuries.

Monitoring changes of the tibialis anterior during dorsiflexion with electromyography, sonomyography, dynamometry and kinematic signals

Dorsiflexion (DF) of the foot plays an essential role in both controlling balance and human gait. Electromyography and Sonomyography can provide information on several aspects of muscle function. The aim was to describe a new method for real-time monitoring of muscular activity, as measured using EMG, muscular architecture, as measured using SMG, force, as measured using dynamometry, and kinematic parameters, as measured using IS during isometric and isotonic contractions of the foot DF. The present methodology may be clinically relevant because it involves a reproducible procedure which allows the function and structure of the foot DF to be monitored.

Identification of genetic susceptibility loci for migraine

Migraine is the common cause of chronic episodic headache, affecting 12%-15% of the Caucasian population (41 million Europeans and some half a million Finns), and causes considerable loss of quality of life to its sufferers, as well as being linked to increased risk for a wide range of conditions, from depression to stroke. Migraine is the 19th most severe disease in terms of disability-adjusted life years, and 9th among women. It is characterized by attacks of headache accompanied by sensitivity to external stimuli lasting 4-72 hours, and in a third of cases by neurological aura symptoms, such as loss of vision, speech or muscle function. The underlying pathophysiology, including what triggers migraine attacks and why they occur in the first place, is largely unknown. The aim of this study was to identify genetic factors associated with the hereditary susceptibility to migraine, in order to gain a better understanding of migraine mechanisms. In this thesis, we report the results of genetic linkage and association analyses on a Finnish migraine patient collection as well as migraineurs from Australia, Denmark, Germany, Iceland and the Netherlands. Altogether we studied genetic information of nearly 7,000 migraine patients and over 50,000 population-matched controls. We also developed a new migraine analysis method called the trait component analysis, which is based on individual patient responses instead of the clinical diagnosis. Using this method, we detected a number of new genetic loci for migraine, including on chromosome 17p13 (HLOD 4.65) and 10q22-q23 (female-specific HLOD 7.68) with significant evidence of linkage, along with five other loci (2p12, 8q12, 4q28-q31, 18q12-q22, and Xp22) detected with suggestive evidence of linkage. The 10q22-q23 locus was the first genetic finding in migraine to show linkage to the same locus and markers in multiple populations, with consistent detection in six different scans. Traditionally, ion channels have been thought to play a role in migraine susceptibility, but we were able to exclude any significant role for common variants in a candidate gene study of 155 ion transport genes. This was followed up by the first genome-wide association study in migraine, conducted on 2,748 migraine patients and 10,747 matched controls followed by a replication in 3,209 patients and 40,062 controls. In this study, we found interesting results with genome-wide significance, providing targets for future genetic and functional studies. Overall, we found several promising genetic loci for migraine providing a promising base for future studies in migraine.

Identification of genetic susceptibility loci for migraine

Migraine is the common cause of chronic episodic headache, affecting 12%-15% of the Caucasian population (41 million Europeans and some half a million Finns), and causes considerable loss of quality of life to its sufferers, as well as being linked to increased risk for a wide range of conditions, from depression to stroke. Migraine is the 19th most severe disease in terms of disability-adjusted life years, and 9th among women. It is characterized by attacks of headache accompanied by sensitivity to external stimuli lasting 4-72 hours, and in a third of cases by neurological aura symptoms, such as loss of vision, speech or muscle function. The underlying pathophysiology, including what triggers migraine attacks and why they occur in the first place, is largely unknown. The aim of this study was to identify genetic factors associated with the hereditary susceptibility to migraine, in order to gain a better understanding of migraine mechanisms. In this thesis, we report the results of genetic linkage and association analyses on a Finnish migraine patient collection as well as migraineurs from Australia, Denmark, Germany, Iceland and the Netherlands. Altogether we studied genetic information of nearly 7,000 migraine patients and over 50,000 population-matched controls. We also developed a new migraine analysis method called the trait component analysis, which is based on individual patient responses instead of the clinical diagnosis. Using this method, we detected a number of new genetic loci for migraine, including on chromosome 17p13 (HLOD 4.65) and 10q22-q23 (female-specific HLOD 7.68) with significant evidence of linkage, along with five other loci (2p12, 8q12, 4q28-q31, 18q12-q22, and Xp22) detected with suggestive evidence of linkage. The 10q22-q23 locus was the first genetic finding in migraine to show linkage to the same locus and markers in multiple populations, with consistent detection in six different scans. Traditionally, ion channels have been thought to play a role in migraine susceptibility, but we were able to exclude any significant role for common variants in a candidate gene study of 155 ion transport genes. This was followed up by the first genome-wide association study in migraine, conducted on 2,748 migraine patients and 10,747 matched controls followed by a replication in 3,209 patients and 40,062 controls. In this study, we found interesting results with genome-wide significance, providing targets for future genetic and functional studies. Overall, we found several promising genetic loci for migraine providing a promising base for future studies in migraine.

Sarcopenia em pacientes idosos com doença renal crônica em hemodiálise

Os pacientes idosos em hemodiálise (HD) são altamente suscetíveis ao desenvolvimento de sarcopenia, devido ao processo natural de envelhecimento e ao catabolismo induzido pelo procedimento de HD. O objetivo deste estudo foi primeiro, avaliar a prevalência de sarcopenia, dinapenia e atrofia muscular em um grupo de pacientes idosos em HD; o segundo, avaliar se os critérios aplicados para o diagnóstico de sarcopenia, propostos por sociedades internacionais, são capazes de distinguir os pacientes com pior condição clínica, estado nutricional e qualidade de vida. Este estudo multicêntrico e transversal incluiu 94 pacientes idosos em HD (> 60 anos) de cinco centros de diálise. Todos os participantes foram submetidos à avaliação antropométrica, de composição corporal, força de preensão manual (FPM), laboratorial e avaliação da condição nutricional através da avaliação subjetiva global de 7 pontos (AGS-7p). Adicionalmente, os participantes responderam um questionário de qualidade de vida. Para o diagnóstico de sarcopenia, foram adotados os critérios propostos por sociedades internacionais, que englobam os parâmetros indicativos de baixa massa muscular e baixa função muscular. Para a massa muscular adotou-se o índice de massa magra (IMM) < percentil 20 para o gênero e faixa etária de uma população de referência, avaliado a partir da massa magra obtida pelo somatório de dobras cutâneas. Para o critério de baixa função muscular, adotou-se a FPM < percentil 10 para o gênero, faixa etária e o braço utilizado de uma população de referência. Os pacientes foram classificados como Sarcopênicos (baixo IMM associado à baixa FPM); Dinapênicos (baixa FPM) e Atrofia muscular (baixo IMM). A sarcopenia estava presente em 13.8% dos pacientes, enquanto a dinapenia foi observada em 37.2% e a atrofia muscular em 35.1%. A sarcopenia foi capaz de distinguir os pacientes que possuíam maior comprometimento do estado nutricional e da composição corporal. O critério de função muscular (isoladamente ou em combinação com a massa muscular) também identificou os pacientes com pior qualidade de vida. Em conclusão, a prevalência de sarcopenia foi observada em 13,8% do grupo. Entretanto, ao usar apenas critérios que indicam redução da força ou massa muscular, esta prevalência aumentou para 30%. A condição de sarcopenia distinguiu pacientes com pior estado nutricional e qualidade de vida.