Resistance training alters skeletal muscle structure and function in human heart failure: effects at the tissue, cellular and molecular levels

Reduced skeletal muscle function in heart failure (HF) patients may be partially explained by altered myofilament protein content and function. Resistance training increases muscle function, although whether these improvements are achieved by correction of myofilament deficits is not known. To address this question, we examined 10 HF patients and 14 controls prior to and following an 18 week high-intensity resistance training programme. Evaluations of wholemuscle size and strength, singlemuscle fibre size, ultrastructure and tension andmyosin-actin cross-bridge mechanics and kineticswere performed. Training improved whole muscle isometric torque in both groups, although therewere no alterations in wholemuscle size or single fibre cross-sectional area or isometric tension. Unexpectedly, training reduced themyofibril fractional area of muscle fibres in both groups. This structural change manifested functionally as a reduction in the number of strongly boundmyosin-actin cross-bridges during Ca2+ activation. When post-training single fibre tension data were corrected for the loss of myofibril fractional area, we observed an increase in tension with resistance training. Additionally, training corrected alterations in cross-bridge kinetics (e. g. myosin attachment time) in HF patients back to levels observed in untrained controls. Collectively, our results indicate that improvements in myofilament function in sedentary elderly with and without HF may contribute to increased whole muscle function with resistance training. More broadly, these data highlight novel cellular and molecular adaptations in muscle structure and function that contribute to the resistance-trained phenotype.