Training one type of striated muscle to counteract failure of another type
Year: 2012
Type: article
Abstract: Chronic diseases are characterized not only by the primary impairments they cause, but also by the disabilities that result from them. This is particularly true for chronic heart failure (CHF). In CHF, the primary defect concerns the impaired pump function of the cardiac muscle. However, not only cardiac muscle function is affected in CHF, but the functioning of skeletal muscle as well. Skeletal muscle dysfunction has been proposed to limit patients during daily life activities by contributing to the development of muscle fatigue. Adaptations in skeletal muscle that might contribute to fatigue include a reduction in muscle strength (Harrington et al. 1997) but also changes in vascular function and local oxygen transport (Esposito et al. 2010). The cellular basis for the reduction in muscle strength in CHF includes alterations at the level of the sarcomere, the smallest contractile unit in muscle. Several studies, in animal models as well as in patients’ tissue, revealed not only quantitative alterations such as loss of sarcomeric proteins, but also qualitative changes including impaired crossbridge kinetics (Miller et al. 2010). In a recent issue of The Journal of Physiology, Toth et al. (2012) addressed the effect of resistance exercise training on sarcomere function in CHF patients. The effect of resistance exercise training had been studied previously, and was found to improve muscle strength and daily life activities. However, although exercise-based rehabilitation is now part of CHF management, the cellular mechanisms that underlie the improved outcome of trained CHF patients remained unknown. Toth et al. examined 10 CHF patients and 14 control subjects prior to and following an 18 week high-intensity resistance training programme. Sarcomere function was studied in demembranated muscle fibres isolated from m. quadriceps biopsies. By employing small-amplitude sinusoidal length perturbations, it was found that resistance training corrects the alterations in crossbridge kinetics in patients back to control values. The authors should be applauded for their approach, which included studies at multiple levels of muscular organization with a variety of state-of-the-art techniques. Notwithstanding the elegance of this study, there are some considerations that should be taken into account. First, the correction of crossbridge kinetics after resistance training in CHF patients did not increase the specific force of fibres, but the observed reduction of myofibril area fraction following training indicated that specific myofibrillar force was increased. However, despite the absence of an effect at the level of the muscle fibre, the force generating capacity of the whole muscle was improved by ∼15% after resistance training in CHF patients. Perhaps longer durations of resistance training or other training regimes such as endurance training (Mandic et al. 2011) are required to also induce significant remodelling at the muscle fibre level, which would result in an overall increase in specific force at the fibre and the whole muscle level. This notion is supported by previous work on healthy subjects from Bottinelli and colleagues (Pansarasa et al. 2009), which showed robust changes in fibre specific force after 1 year of resistance training. Another issue that should be taken into account is the potential ‘confounding’ effect of disease progression during the ∼4 months of training. The 5 year survival rate in CHF patients is ∼50%. This suggests that during the 4 months of training, muscle fibre function might have been negatively affected by the disease. Perhaps this masked the effects of training on the outcome parameters. Second, the specific force of muscle fibres at baseline (prior to training) was not different between patients and control subjects. This finding might appear to be not in line with previous studies, which revealed a decrease of fibre specific force in CHF patients (Szentesi et al. 2005). However, this discrepancy can at least partly be explained by subject selection: in contrast to previous studies, the patients and control subjects studied by Toth et al. were carefully matched, even for activity levels and co-morbidity. Thus, the work by Toth and colleagues highlights the importance of studying controls that are well matched to the patients, but might also suggest that CHF per se does not greatly affect muscle fibre function. Caution should be exercised, though, because it cannot be ruled out that the group size in the present study was not sufficiently large to detect differences to explain the ∼15% improvement in global muscle function. This is further highlighted by the magnitude (up to ∼30%) of reported age- and/or activity-related alterations in for instance specific force production or power output. In defence of the authors, one should appreciate the difficulty of recruiting a large number of patients for a study with the labour-intensive design as employed by Toth and coworkers. In summary, the work by Toth and colleagues raises interesting and important questions about the mechanism underlying muscle weakness in CHF, and the effect of resistance training on strength. We are of the opinion that in order to conclusively address these questions, multiple research groups might need to combine forces to study a large cohort of CHF patients. This will also allow control for the effect of disease progression by including a CHF group that does not undergo training, and could also provide more mechanistic insight by analysis of cytokine levels and biomarkers of heart failure progression.
Source: The Journal of Physiology
Authors: Ger J. M. Stienen, Coen A. C. Ottenheijm
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1970320595