title: Skeletal muscle alterations in chronic heart failure: differential effects on quadriceps and diaphragm.
abstract: BACKGROUND
  Chronic heart failure (CHF) results in limb and respiratory muscle weakness, which contributes to exercise intolerance and increased morbidity and mortality, yet the molecular mechanisms remain poorly understood. Therefore, we aimed to compare parameters of antioxidative capacity, energy metabolism, and catabolic/anabolic balance in diaphragm and quadriceps muscle in an animal model of CHF.
  
  
  METHODS
  Ligation of the left anterior descending coronary artery (n = 13) or sham operation (n = 11) was performed on Wistar Kyoto rats. After 12 weeks, echocardiography and invasive determination of maximal rates of left ventricular (LV) pressure change were performed. Antioxidative and metabolic enzyme activities and expression of catabolic/anabolic markers were assessed in quadriceps and diaphragm muscle.
  
  
  RESULTS
  Ligated rats developed CHF (i.e. severe LV dilatation, reduced LV ejection fraction, and impaired maximal rates of LV pressure change; P < 0.001). There was a divergent response for antioxidant enzymes between the diaphragm and quadriceps in CHF rats, with glutathione peroxidase and manganese superoxide dismutase activity increased in the diaphragm but reduced in the quadriceps relative to shams (P < 0.01). Metabolic enzymes were unaltered in the diaphragm, but cytochrome c oxidase activity (P < 0.01) decreased and lactate dehydrogenase activity (P < 0.05) increased in the quadriceps of CHF animals. Protein expression of the E3 ligase muscle ring finger 1 and proteasome activity were increased (P < 0.05) in both the diaphragm and quadriceps in CHF rats compared with shams.
  
  
  CONCLUSIONS
  Chronic heart failure induced divergent antioxidative and metabolic but similar catabolic responses between the diaphragm and quadriceps. Despite the quadriceps demonstrating significant impairments in CHF, apparent beneficial adaptations of an increased antioxidative capacity were induced in the diaphragm. Nevertheless, muscle ring finger 1 and proteasome activity (markers of protein degradation) were elevated and oxidative enzyme activity failed to increase in the diaphragm of CHF rats, which suggest that a myopathy is likely present in respiratory muscle in CHF, despite its constant activation.
authors.affiliation: Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center Leipzig, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Mangner
authors.affiliation: Department of Internal Medicine/Cardiology, Clinic Altenburg Altenburg, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Weikert
authors.affiliation: Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center Leipzig, Germany.
authors.forename: T Scott
authors.initials: TS
authors.lastname: Bowen
authors.affiliation: Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center Leipzig, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Sandri
authors.affiliation: Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center Leipzig, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Höllriegel
authors.affiliation: Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center Leipzig, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Erbs
authors.affiliation: Department of Cardiology and Angiology, Clinic Links der Weser Bremen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Hambrecht
authors.affiliation: Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center Leipzig, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.affiliation: Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center Leipzig, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.affiliation: University Hospital-Martin Luther University of Halle/Wittenberg Halle, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gielen
authors.affiliation: Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center Leipzig, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
keywords: Antioxidative enzymes; CHF; Congestive heart failure; MuRF-1