title: Exercise training in patients with advanced chronic heart failure (NYHA IIIb) promotes restoration of peripheral vasomotor function, induction of endogenous regeneration, and improvement of left ventricular function.
abstract: BACKGROUND
  Attenuated peripheral perfusion in patients with advanced chronic heart failure (CHF) is partially the result of endothelial dysfunction. This has been causally linked to an impaired endogenous regenerative capacity of circulating progenitor cells (CPC). The aim of this study was to elucidate whether exercise training (ET) affects exercise intolerance and left ventricular (LV) performance in patients with advanced CHF (New York Heart Association class IIIb) and whether this is associated with correction of peripheral vasomotion and induction of endogenous regeneration.
  
  
  RESULTS
  Thirty-seven patients with CHF (LV ejection fraction 24+/-2%) were randomly assigned to 12 weeks of ET or sedentary lifestyle (control). At the beginning of the study and after 12 weeks, maximal oxygen consumption (Vo(2)max) and LV ejection fraction were determined; the number of CD34(+)/KDR(+) CPCs was quantified by flow cytometry and CPC functional capacity was determined by migration assay. Flow-mediated dilation was assessed by ultrasound. Capillary density was measured in skeletal muscle tissue samples. In advanced CHF, ET improved Vo(2)max by +2.7+/-2.2 versus -0.8+/-3.1 mL/min/kg in control (P=0.009) and LV ejection fraction by +9.4+/-6.1 versus -0.8+/-5.2% in control (P<0.001). Flow-mediated dilation improved by +7.43+/-2.28 versus +0.09+/-2.18% in control (P<0.001). ET increased the number of CPC by +83+/-60 versus -6+/-109 cells/mL in control (P=0.014) and their migratory capacity by +224+/-263 versus -12+/-159 CPC/1000 plated CPC in control (P=0.03). Skeletal muscle capillary density increased by +0.22+/-0.10 versus -0.02+/-0.16 capillaries per fiber in control (P<0.001).
  
  
  CONCLUSIONS
  Twelve weeks of ET in patients with advanced CHF is associated with augmented regenerative capacity of CPCs, enhanced flow-mediated dilation suggestive of improvement in endothelial function, skeletal muscle neovascularization, and improved LV function. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique Identifier: NCT00176384.
authors.affiliation: Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany. Sandra.Erbs@medizin.uni-leipzig.de
authors.forename: Sandra
authors.initials: S
authors.lastname: Erbs
authors.forename: Robert
authors.initials: R
authors.lastname: Höllriegel
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.forename: Ephraim B
authors.initials: EB
authors.lastname: Beck
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.forename: Stephan
authors.initials: S
authors.lastname: Gielen
authors.forename: Sven
authors.initials: S
authors.lastname: Möbius-Winkler
authors.forename: Marcus
authors.initials: M
authors.lastname: Sandri
authors.forename: Nicolle
authors.initials: N
authors.lastname: Kränkel
authors.forename: Rainer
authors.initials: R
authors.lastname: Hambrecht
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
mesh_terms: D000368:Aged; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000502:physiology*; D005081:Exercise Therapy / Q000379:methods*; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000534:rehabilitation*; D006801:Humans; D007866:Leg / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D011446:Prospective Studies; D020127:Recovery of Function; D012039:Regional Blood Flow / Q000502:physiology; D018570:Risk Assessment; D057185:Sedentary Behavior; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000502:physiology*; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000502:physiology; D014666:Vasomotor System / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology