Apoptosis in the skeletal muscle of patients with heart failure: investigation of clinical and biochemical changes

Objective-To investigate the contribution of apoptosis in the development o f the skeletal myopathy in chronic heart failure. Design-The electrophoretic pattern of myosin heavy chains (MHC), fibre cros s sectional area, number of in situ nick end labelling (TUNEL) positive apo ptotic myocyte nuclei, and the tissue levels of caspase-3, Bcl-2, and ubiqu itin were determined in biopsies taken from the vastus lateralis muscle. Th e study involved nine patients with severe chronic heart failure caused by ischaemic heart disease and hibernating myocardium and five controls. Results-In chronic heart failure patients the vastus lateralis showed a sig nificant increase of MHC2a and MHC2b and a greater degree of fibre atrophy, as demonstrated by the decreased cross sectional area. There was also an i ncreased number of TUNEL positive apoptotic myocyte nuclei. Tissue concentr ations of Bcl-2 were decreased, while those of caspase-3 and ubiquitin were increased. Peak oxygen consumption (Vo(2)) was negatively correlated with the number of TUNEL positive nuclei and the fibre cross sectional area. The re was a correlation between the number df apoptotic nuclei and the fibre c ross sectional area, but no correlation between myosin heavy chains and num ber of apoptotic nuclei. (C)onclusions-Myocyte apoptosis occurs in the skeletal muscle of patients w ith chronic heart failure, and its magnitude is associated with the severit y of exercise capacity limitation and the degree of muscle atrophy. Muscle atrophy contributes to the limitation of exercise capacity, together with t he increased synthesis of fast, more fatiguable myosin heavy chains.