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

Abstract

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 whole muscle size and strength, single muscle fibre size, ultrastructure and tension and myosin-actin cross-bridge mechanics and kinetics were performed. Training improved whole muscle isometric torque in both groups, although there were no alterations in whole muscle size or single fibre cross-sectional area or isometric tension.Unexpectedly, training reduced the myofibril fractional area of muscle fibres in both groups. This structural change manifested functionally as a reduction in the number of strongly bound myosin-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.

Figures

Figure 1

Skeletal muscle fibre myofilament ultrastructure in controls (n = 5) and HF patients (n = 4) before (pre) and after (post) resistance exercise training. Data represent mean ± SEM. *P < 0.01 training effect; **P = 0.07 training effect. Representative electron micrographs from a control volunteer are shown to depict the change in myofibrillar fractional area with training. Bar represents 0.5 μm.

Figure 2

Single skeletal muscle fibre Ca2+-activated tension and dynamic stiffness data from MHC I fibres in controls (n = 10) and HF patients (n = 9) at 15°C and 0.25 mm Pi before (pre) and after (post) resistance exercise training. The number of fibres studied is shown at the base of each bar. Data for tension and absolute stiffness are expressed relative to muscle fibre cross-sectional area.

Figure 3

Single skeletal muscle fibre Ca2+-activated tension and dynamic stiffness data from MHC IIA fibres in controls (n = 9) and HF patients (n = 9) at 15°C and 0.25 mm Pi before (pre) and after (post) resistance exercise training. Note that there was one less control volunteer available for MHC IIA fibres vs. MHC I fibres (Fig. 2) because one control had no MHC IIA fibres during pre- or post-training evaluations. The number of fibres studied is shown at the base of each bar. Data for tension and absolute stiffness are expressed relative to muscle fibre cross-sectional area.

Figure 4

Ca2+-activated tension data for MHC I (A) and IIA (B) fibres at 25°C and 5 mm Pi before (pre) and after (post) resistance exercise training. Sample sizes for A and B are similar to those designated in Figs 2 and 3, respectively. The number of fibres studied is shown at the base of each bar. Data for tension are expressed relative to muscle fibre cross-sectional area.

Figure 5

Sinusoidal analysis model parameter response for Ca2+-activated MHC I fibres in controls (n = 9) and HF patients (n = 8), including A, B and C components, before (pre) and after (post) resistance exercise training. Each italicized letter represents the magnitude of its respective process (A, B or C) expressed relative to fibre cross-sectional area. The number of fibres studied is shown at the base of each bar. *P < 0.02 for training effect.

Figure 6

Sinusoidal analysis model parameter response for Ca2+-activated MHC I fibres in controls (n = 9) and HF patients (n = 8), including k, myosin rate of force production (2πb) and ton ((2πc)−1) components, before (pre) and after (post) resistance exercise training. The number of fibres studied is shown at the base of each bar. **P = 0.06 for group × training effect.

Figure 7

Sinusoidal analysis model parameter response for Ca2+-activated MHC IIA fibres in controls (n = 8) and HF patients (n = 8), including A, B and C components, before (pre) and after (post) resistance exercise training. Each italicized letter represents the magnitude of its respective process expressed relative to fibre cross-sectional area. Note that there was one less control volunteer available for MHC IIA fibres vs. MHC I fibres (Figs 5 and 6) because one control had no MHC IIA fibres during pre- or post-training evaluations. The number of fibres studied is shown at the base of each bar. *P < 0.05 for training effect.

Figure 8

Sinusoidal analysis model parameter response for Ca2+-activated MHC IIA fibres in controls (n = 8) and HF patients (n = 8), including k, myosin rate of force production (2πb) and ton ((2πc)−1) components, before (pre) and after (post) resistance exercise training. Note that there was one less control volunteer available for MHC IIA fibres vs. MHC I fibres (Figs 4 and 5) because one control had no MHC IIA fibres during pre- or post-training evaluations. The number of fibres studied is shown at the base of each bar. *P < 0.05 for group × training effect; **P = 0.06 for group × training effect.