ISSN 0100-879X Volume 44 (11) 1070-1193 November 2011
BIOMEDICAL SCIENCES AND CLINICAL INVESTIGATION
www.bjournal.com.br
Braz J Med Biol Res, November 2011, Volume 44(11) 1070-1079 doi: 10.1590/S0100-879X2011007500125
Functional and morphological effects of resistance exercise on disuse-induced skeletal muscle atrophy H. Nicastro, N.E. Zanchi, C.R. da Luz and A.H. Lancha Jr.
The Brazilian Journal of Medical and Biological Research is partially financed by
Institutional Sponsors
Campus Ribeirão Preto
Explore High - Performance MS Orbitrap Technology In Proteomics & Metabolomics Faculdade de Medicina de Ribeirão Preto analiticaweb.com.br
S C I E N T I F I C
All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License
Brazilian Journal of Medical and Biological Research (2011) 44: 1070-1079 ISSN 0100-879X Review
Functional and morphological effects of resistance exercise on disuse-induced skeletal muscle atrophy H. Nicastro1, N.E. Zanchi2, C.R. da Luz1 and A.H. Lancha Jr.1 1Laboratório
de Nutrição e Metabolismo Aplicados a Atividade Motora, Escola de Educação Física e Esporte, Universidade de São Paulo, São Paulo, SP, Brasil 2Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil
Abstract The reduction of skeletal muscle loss in pathological states, such as muscle disuse, has considerable effects in terms of rehabilitation and quality of life. Since there is no currently effective and safe treatment available for skeletal muscle atrophy, the search for new alternatives is necessary. Resistance exercise (RE) seems to be an important tool in the treatment of disuse-induced skeletal muscle atrophy by promoting positive functional (strength and power) and structural (hypertrophy and phenotypic changes) adaptive responses. Human and animal studies using different types of resistance exercise (flywheel, vascular occlusion, dynamic, isometric, and eccentric) have obtained results of great importance. However, since RE is a complex phenomenon, lack of strict control of its variables (volume, frequency, intensity, muscle action, rest intervals) limits the interpretation of the impact of the manipulation on skeletal muscle remodeling and function under disuse. The aim of this review is to critically describe the functional and morphological role of resistance exercise in disuse-induced skeletal muscle atrophy with emphasis on the principles of training. Key words: Resistance exercise; Vascular occlusion; Eccentric exercise; Disuse; Atrophy
Introduction The morphological and functional adaptations to resistance exercise (RE) have been well described, among them the positive responses of the neuromuscular system (neural adaptations) (1,2), muscle architecture (angle of pennation), biochemical composition (myosin heavy chain (MHC) isoform transition) (3,4), and the accumulation of myofibrillar proteins (5,6). These responses may occur according to the nature of the stimulus applied (i.e., the variables of the training program). In contrast to the positive response of muscle remodeling observed in some RE protocols, skeletal muscle atrophy is characterized by severe loss of muscle mass, specifically of contractile proteins (7). Generally, skeletal muscle atrophy can be defined as the unintentional loss of muscle mass due to catabolic states (8). Pathologically, there are some conditions that can induce it, such as cancer (8), sepsis (9), AIDS (10), diabetes (11), use of glucocorticoids (12), inactivity/disuse (13), chronic renal failure (14), and sarcopenia (15). In animals, experimental
models of immobilization (16), use of corticosteroids or synthetic glucocorticoids (12), denervation (17), and even obesity (18) are used to mimic the catabolic states observed in humans in order to investigate the mechanisms behind the phenomenon. Several studies using atrophic models have been performed with animals because better control of variables is possible. They have focused on molecular mechanisms responsible for modulating skeletal muscle protein metabolism (19). However, although the parameters investigated at the cellular level are relevant to the design of new interventions, little attention has been given to the principles of RE in atrophic conditions, i.e., studies have not evaluated the impact of training variable manipulation and/or control and application of different RE protocols on the functional and structural parameters of skeletal muscle in atrophic conditions. It is supposed that similar protocols of RE in different atrophic conditions may promote distinct
Correspondence: H. Nicastro, Laboratório de Nutrição e Metabolismo Aplicados a Atividade Motora, Escola de Educação Física e Esporte, USP, São Paulo, SP, Brasil. Fax: +55-11-3091-3136. E-mail:
[email protected] Received April 12, 2011. Accepted September 9, 2011. Available online September 23, 2011. Published November 14, 2011. Braz J Med Biol Res 44(11) 2011
www.bjournal.com.br
Resistance exercise and disuse-induced muscle atrophy
adaptive responses since these catabolic states primarily differ in terms of cause (hereditary and non-hereditary) and cellular mechanisms responsible for the loss of muscle mass. Therefore, although there are several models and conditions able to induce muscle atrophy and RE may counteract muscle wasting and strength loss, the optimal characterization of RE in each of these conditions has not been completely elucidated. Therefore, the purpose of this report is to review the effects of RE and its variables on the functional and structural parameters of non-hereditary and non-inflammatory skeletal muscle atrophic conditions characterized by muscle disuse such as inactivity (immobilization, bed rest and post-surgical cases) and lack of gravity. Worthy of note, the RE variables are approached separately in order to discuss the effectiveness of their characterization according to the model of RE. It is important to note that short periods of immobilization may result in significant strength loss but may not induce significant muscle atrophy (20). Thus, for this review we selected studies whose experimental design of muscle disuse resulted in significant skeletal muscle atrophy and loss of muscle function (strength). Considering also that immobilization protocols are more aggressive in terms of strength loss (21-23) than models of suspension or bed rest (24-26), the atrophic states were discussed separately and according to the model of training applied.
Why study the effect of resistance exercise on skeletal muscle atrophy? One of the functional focuses of RE is to reduce muscle weakness and/or increase physical capacity (27). RE may also be considered a non-pharmacological treatment. For example, in elderly subjects muscle function and its ability to generate strength have been used as predictors of life expectancy (28). Recently, Spiering et al. (29) reported that the manipulation of RE variables promotes “fingerprints” in skeletal muscle at the cellular and molecular levels. Consequently, these “fingerprints” may be reflected on the functional and structural level and can be characterized, in general, as positive, negative or neutral adaptive responses. Thus, RE is a highly complex phenomenon and the manipulation of its variables can promote unique responses. The knowledge of such principles is extremely important for developing an effective training program.
Magnitude and functionality of different types of resistance exercise Among the models of RE most commonly used in disuse atrophic states are flywheel (30-34), vascular occlusion (VO) (35), and conventional RE consisting of concentric/eccentric or isometric muscle actions (20,36,37). It is important to emphasize that the composition of these types of RE differs in terms of intensity and volume. For example, VO is www.bjournal.com.br
1071
a protocol characterized by low-moderate intensity, while flywheel and conventional RE usually consist of moderatehigh intensity protocols. Muscle actions performed during flywheel RE are primarily eccentric and can be easily manipulated in conventional RE. Some studies have used unilateral immobilization both in humans and animals with concurrent contralateral training. In this condition, it is essential to note that the crosseducation phenomenon is present and may directly influence the functional and structural responses of the atrophied limb through neural adaptations (38-40). Therefore, unilateral immobilization is a condition that should be carefully evaluated. Furthermore, some of these studies have failed by using only internal control. Tables 1 and 2 summarize the main findings of published studies, highlighting the training models and their variables. Flywheel resistance exercise Flywheel RE is characterized by the lack of gravity. This type of RE has been applied in atrophic states induced by lack of gravity (i.e., during space missions), bed rest, and immobilization of the lower limbs. Tesch et al. (41), in a study of 4 individuals after 1 day of space mission, demonstrated that the isometric, concentric and eccentric strengths of the knee extensors were significantly reduced by approximately 10.2, 8.7, and 11.5%, respectively. Hence, the cross-sectional area (CSA) of the femoral quadriceps and gluteus femoral muscles was reduced by 8.0 and 8.5%, respectively. This same research group noted that individuals submitted to lower limb immobilization who performed RE (knee extension) in a flywheel for 5 weeks showed a significant gain of 7.7% in quadriceps volume and maintenance of basal strength (isometric strength at 90° and 120°) when compared with the untrained immobilized group (31). Rittweger et al. (33) chronically evaluated the role of flywheel RE in healthy young individuals submitted to bed rest with -6 degrees head-down for 90 days and observed that the trained group showed maintenance of 8.3% of thigh CSA when compared to the control group. Later, these investigators assessed the effect of this model of RE on the same experimental design in terms of vertical jump power 4, 7, 14, 90, and 180 days after 90 days of bed rest and observed that the delta of vertical jump amplitude and peak power after 4 days were -13 cm and -12.9 W/kg reduced in the control group and only -4.2 cm and -4 W/ kg reduced in the trained group. Additionally, vertical jump amplitude and peak power were completely restored after 72 and 18 days, respectively, in the trained group while for the control group this occurred after 163 and 140 days (34). This model was further tested by Trappe et al. (32) who studied individuals submitted to 84 days of bed rest with -6 degrees head-down performing RE simultaneously. These investigators observed that the trained group showed preservation of size and function of the vastus lateralis muscle (isometric and isotonic strength), a 6% increase in MHC Braz J Med Biol Res 44(11) 2011
H. Nicastro et al.
1072
IIa content and 19% of hybrid MHC I/IIa compared to 29% for the untrained group and did not show any decrease in fiber type I or IIa areas. Although the authors did not assess the phenotypic profile throughout the study, the increase of MHC I/IIa demonstrates that the muscle was in remodeling and adaptation processes at the time of evaluation and a further increase of MHC IIa content could be expected. Maintenance of power, peak power, and a 13% increase in the contractile activity of type IIa fibers were also observed. The studies of Trappe et al. (32) and Rittweger et al. (34)
used the same model of muscle atrophy and tested a similar model of RE except for its variables, demonstrating the specificity of the mechanical stimulus. In an experimental model, Fluckey et al. (42) developed a training apparatus for rats similar to the flywheel used in humans, with the detail that the animals trained in the hindlimb suspension position. This point is important because exposure to body overload could have masked the magnitude of the results. Hindlimb-suspended animals who trained for 4 weeks had higher absolute and relative soleus
Table 1. Effects of different forms of resistance exercise on functional and morphological responses of disuse-induced atrophied skeletal muscle. Study
Resistance exercise
Results
HUMANS Akima et al. (30) Ohta et al. (35)
Dynamic Isometric with VO
Increase of biceps femoris CSA and semitendinosus muscles Knee extensors 60°/s concentric strength: maintenance of 26% 180°/s concentric strength: maintenance of 19.4% 60° isometric strength: maintenance of 1.9% Flexor muscles 60°/s concentric strength: maintenance of 4.4% 180°/s concentric strength: maintenance of 12.8% 60° isometric strength: maintenance of 13.1%
Jones et al. (36) Tesch et al. (31)
Dynamic Flywheel
Restoration of skeletal muscle mass Increase of 7.7% of quadriceps muscle volume Maintenance of 90° and 120° isometric strength
Trappe et al. (32)
Flywheel
Maintenance of size and function (isometric and isotonic strengths) of vastus lateralis muscle Increase of 6% of MHC IIa and MHC I/IIa isoforms
Rittweger et al. (33) Rittweger et al. (34)
Flywheel Flywheel
Farthing et al. (20) Trappe et al. (37)
Isometric Dynamic
Maintenance of 8.3% of tight CSA Maintenance of 8.8 cm and 8.9 W/kg in vertical jump amplitude and peak power after 4 days Restoration of amplitude and power of vertical jump after 72 and 18 days, respectively Maintenance of isometric strength of an immobilized limb Reduction of 32% of peak power Reduction of 13% of calf volume Reduction of 15% of soleus muscle Reduction of 10% of gastrocnemius muscle Increase of soleus and gastrocnemius MHC IIa isoform
RATS Fluckey et al. (42) Dupont-Versteegden et al. (43) Haddad et al. (52) Adams et al. (53)
Flywheel Flywheel Dynamic Concentric/Eccentric/Isometric
Greater absolute and relative soleus muscle mass compared to an untrained group Increase of absolute and relative soleus and gastrocnemius muscles mass compared to an untrained group No significant results Increase of absolute and relative gastrocnemius muscle mass compared to the contralateral limb Accumulation of myofibrillar proteins in trained limb
CSA = cross-sectional area; MHC = myosin heavy chain; VO = vascular occlusion. Braz J Med Biol Res 44(11) 2011
www.bjournal.com.br
Resistance exercise and disuse-induced muscle atrophy
1073
Table 2. Description of training variables of different resistance exercise models for disuse-induced skeletal muscle atrophy. Study
Condition
Duration
RE model
Contralateral training?
Volume (sets x repetitions)
Frequency
Intensity
Rest interval
HUMANS Akima et al. (30)
Bed rest
20 days
Dynamic
No
3 x 10 (Session 1)
2 sessions/day (20 sessions)
90% 1RM (Session 1/day) 40% 1RM (Session 2/day)
1 min (between sets)
Until exhaustion (Session 2) Ohta et al. (35)
Reconstruction of anterior cruciate ligament
16 weeks after surgery
Vascular occlusion (isometric)
Yes
2-3 x 20
6 times/week
Straight leg raising exercise Week 1: no load Weeks 2-4: 1 kg Weeks 5-8: 2 kg Half-squat exercise Weeks 5-6: no load Weeks 7-8: 4-6 kg Weeks 9-12: 8-10 kg Weeks 13-16: 12-14 kg
N/R
Jones et al. (36)
Immobilization
6 weeks of training after 2 weeks of immobilization
Dynamic
No
5 x 30
3 times/week
Maximal intensity
1 min (between sets)
Tesch et al. (31)
Immobilization
5 weeks
Flywheel
No
4x7
2-3 times/week
N/R
2 min (between sets)
Trappe et al. (32)
Bed rest
84 days
Flywheel
No
4x7
2-3 times/week
N/R
2 min (between sets)
Rittweger et al. (33)
Bed rest
90 days
Flywheel
No
4 x 14
Every 3 days beginning on the 5th day of rest
N/R
2 min (between sets) 5 min (between exercises)
Rittweger et al. (34)
Bed rest
90 days
Flywheel
No
4 x 14
Every 3 days beginning on the 5th day of rest
N/R
2 min (between sets) 5 min (between exercises)
Farthing et al. (20)
Immobilization
21 days
Isometric
Yes
3 x 8 progressively to 6 x 8
5 times/week
N/R
N/R
Trappe et al. (37)
Absence of gravity
6 months
Dynamic
No
3-6 x 12-20
3-6 times/week
N/R
N/R
Hindlimb suspension
28 days
Flywheel
No
2 x 21
3 times/week
123.4 ± 7.2 g peak force for each repetition
N/R
Dupont-Versteegden et al. (43)
Hindlimb suspension
14 days
Flywheel
No
2 x 25
6 sessions
N/R
N/R
Haddad et al. (52)
Hindlimb suspension
6 days
Isometric
Yes
4 x 10
3 sessions
