title: Effect of exercise training on skeletal muscle fibre characteristics in men with chronic heart failure. Correlation between skeletal muscle alterations, cytokines and exercise capacity.
abstract: BACKGROUND
  In patients with congestive heart failure (CHF) there is a shift from aerobic type I muscle fibres to less aerobic type II fibres. Exercise training has been shown to have beneficial effects on exercise performance, peripheral pathology and the neurohumoral profile in stable patients with CHF. This study evaluated the effect of a 3 month exercise training program on skeletal muscle characteristics and the correlation of these to cytokines and exercise capacity in CHF patients.
  
  
  METHODS
  Skeletal muscle biopsies for enzyme-histochemical analysis were performed in 15 CHF patients in New York Heart Association classes II-III, with a mean ejection fraction of 33+/-5% before and after a 12 week training period. The patients were trained for 30 min, five times a week at 80% of the peak heart rate achieved at baseline ergometer cycle test. Fifteen healthy men were used as controls. Plasma samples were examined by enzyme immunoassays for levels of pro-inflammatory cytokines.
  
  
  RESULTS
  (a) At baseline we found muscle atrophy in five of the patients. The percent area of type I fibres (40.7+/-12.0 vs. 56.4+/-11.0%, P<0.05) and the thickness of type IIA (56.10+/-7.8 vs. 71.6+/-11.9 microm, P<0.001) and B-fibres (49.0+/-8.9 vs. 63.9+/-10.6 microm, P<0.001) were reduced, whereas the percent area of type IIA fibres (52.1+/-13.3 vs. 36.4+/-9.9%, P<0.05) was increased in heart failure patients compared to healthy controls. There was a modest correlation between fibre thickness and the level of interleukin 6 (r=-0.657, P=0.008). (b) After exercise training there was a reduction in muscle area examined by light-microscopy, measured as a percentage of field (-2.7, P=0.003) with an concomitant increase in interstitium. This reduction correlated to the increase in the 6-min walk test (r=-0.558, P=0.031). The thickness of type IIB fibres increased (+5.6 microm, P=0.068) and the area of type I fibres decreased (-6.1%, P=0.062).
  
  
  CONCLUSIONS
  Patients with CHF have a relatively increased area of type IIA fibres and a relatively decreased area of type I fibres compared to healthy individuals. The thickness of type IIA and type IIB fibres is decreased compared to normal individuals. A modest negative correlation between the level of interleukin 6 and fibre thickness at baseline, suggests that inflammatory cytokines may be involved in the pathogenesis of the CHF related myopathy. A significant correlation between the reduction of muscle area, with increased interstitum, and the increase in the 6-min walk test may indicate that the improvement is due to increased capillary density permitting better flow reserve to exercising muscles.
authors.affiliation: Cardiology Division, Central Hospital in Rogaland, P.O. Box 8100, N4001 Stavanger, Norway. al-i-lar@online.no
authors.forename: Alf Inge
authors.initials: AI
authors.lastname: Larsen
authors.forename: Sigurd
authors.initials: S
authors.lastname: Lindal
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Ingrid
authors.initials: I
authors.lastname: Toft
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Aarsland
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dickstein
mesh_terms: D000368:Aged; D001706:Biopsy; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood*; D005081:Exercise Therapy; D017079:Exercise Tolerance / Q000502:physiology; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption / Q000502:physiology; D013223:Statistics as Topic; D013318:Stroke Volume / Q000502:physiology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016138:Walking
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha