title: Capillary density of skeletal muscle: a contributing mechanism for exercise intolerance in class II-III chronic heart failure independent of other peripheral alterations.
abstract: OBJECTIVE
  The study was conducted to determine if the capillary density of skeletal muscle is a potential contributor to exercise intolerance in class II-III chronic heart failure (CHF).
  
  
  BACKGROUND
  Previous studies suggest that abnormalities in skeletal muscle histology, contractile protein content and enzymology contribute to exercise intolerance in CHF.
  
  
  METHODS
  The present study examined skeletal muscle biopsies from 22 male patients with CHF compared with 10 age-matched normal male control patients. Aerobic capacities, myosin heavy chain (MHC) isoforms, enzymes, and capillary density were measured.
  
  
  RESULTS
  The patients with CHF demonstrated a reduced peak oxygen consumption when compared to controls (15.0+/-2.5 vs. 19.8+/-5.0 ml x kg(-1) x min(-1), p <0.05). Using cell-specific antibodies to directly assess vascular density, there was a reduction in capillary density in CHF measured as the number of endothelial cells/fiber (1.42+/-0.28 vs. 1.74+/-0.35, p = 0.02). In CHF, capillary density was inversely related to maximal oxygen consumption (r = 0.479, p = 0.02). The MHC IIx isoform was found to be higher in patients with CHF versus normal subjects (28.5+/-13.6 vs. 19.5+/-9.4, p <0.05).
  
  
  CONCLUSIONS
  There was a significant reduction in microvascular density in patients with CHF compared with the control group, without major differences in other usual histologic and biochemical aerobic markers. The inverse relationship with peak oxygen consumption seen in the CHF group suggests that a reduction in microvascular density of skeletal muscle may precede other skeletal muscle alterations and play a critical role in the exercise intolerance characteristic of patients with CHF.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. Dusch001@mc.duke.edu
authors.forename: B D
authors.initials: BD
authors.lastname: Duscha
authors.forename: W E
authors.initials: WE
authors.lastname: Kraus
authors.forename: S J
authors.initials: SJ
authors.lastname: Keteyian
authors.forename: M J
authors.initials: MJ
authors.lastname: Sullivan
authors.forename: H J
authors.initials: HJ
authors.lastname: Green
authors.forename: F H
authors.initials: FH
authors.lastname: Schachat
authors.forename: A M
authors.initials: AM
authors.lastname: Pippen
authors.forename: C A
authors.initials: CA
authors.lastname: Brawner
authors.forename: J M
authors.initials: JM
authors.lastname: Blank
authors.forename: B H
authors.initials: BH
authors.lastname: Annex
mesh_terms: D001706:Biopsy; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002196:Capillaries / Q000473:pathology*; D002452:Cell Count; D004452:Echocardiography; D017079:Exercise Tolerance / Q000502:physiology*; D015637:Gated Blood-Pool Imaging; D006333:Heart Failure / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D010101:Oxygen Consumption; D011379:Prognosis; D013318:Stroke Volume
chemical_list: D017871:Calcium-Calmodulin-Dependent Protein Kinases