title: Apoptosis in the skeletal muscle of patients with heart failure: investigation of clinical and biochemical changes.
abstract: OBJECTIVE
  To investigate the contribution of apoptosis in the development of the skeletal myopathy in chronic heart failure.
  
  
  METHODS
  The electrophoretic pattern of myosin heavy chains (MHC), fibre cross sectional area, number of in situ nick end labelling (TUNEL) positive apoptotic myocyte nuclei, and the tissue levels of caspase-3, Bcl-2, and ubiquitin were determined in biopsies taken from the vastus lateralis muscle. The 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 significant increase of MHC(2a) and MHC(2b) and a greater degree of fibre atrophy, as demonstrated by the decreased cross sectional area. There was also an increased number of TUNEL positive apoptotic myocyte nuclei. Tissue concentrations 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. There was a correlation between the number of apoptotic nuclei and the fibre cross sectional area, but no correlation between myosin heavy chains and number of apoptotic nuclei.
  
  
  CONCLUSIONS
  Myocyte apoptosis occurs in the skeletal muscle of patients with chronic heart failure, and its magnitude is associated with the severity of exercise capacity limitation and the degree of muscle atrophy. Muscle atrophy contributes to the limitation of exercise capacity, together with the increased synthesis of fast, more fatiguable myosin heavy chains.
authors.affiliation: First Department of Internal Medicine, Venice City Hospital, Venice, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Vescovo
authors.forename: M
authors.initials: M
authors.lastname: Volterrani
authors.forename: R
authors.initials: R
authors.lastname: Zennaro
authors.forename: M
authors.initials: M
authors.lastname: Sandri
authors.forename: C
authors.initials: C
authors.lastname: Ceconi
authors.forename: R
authors.initials: R
authors.lastname: Lorusso
authors.forename: R
authors.initials: R
authors.lastname: Ferrari
authors.forename: G B
authors.initials: GB
authors.lastname: Ambrosio
authors.forename: L
authors.initials: L
authors.lastname: Dalla Libera
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D017079:Exercise Tolerance; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D018763:Muscle Fatigue; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D010101:Oxygen Consumption; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012044:Regression Analysis; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D014452:Ubiquitins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D018995:Myosin Heavy Chains