Exercise training in chronic heart failure: correlation between reduced local inflammation and improved oxidative capacity in the skeletal muscle.
BACKGROUND
Chronic heart failure (CHF) is accompanied by an inflammatory activation which occurs both systemically and in the skeletal muscle. Exercise training has been shown to reduce the local expression of cytokines and inducible nitric oxide synthase (iNOS) in muscle biopsies of CHF patients. INOS-derived NO can inhibit oxidative phosphorylation and contribute to skeletal muscle dysfunction in CHF.


METHODS
To investigate the correlation between changes in local iNOS expression associated with regular exercise and changes in aerobic enzyme activities in the skeletal muscle of patients with CHF. Twenty male CHF patients [ejection fraction 25% (SE 2), age 54 (SE 2) years] were randomized to a training (n=10) or a control group (C, n=10).


METHODS
At baseline and after 6 months skeletal muscle iNOS expression was measured by real-time polymerase chain reaction. INOS protein and protein nitrosylation were assessed by immunohistochemistry. Cytochrome c oxidase (COX) activity was quantified electrochemically using the Clark oxygen electrode.


RESULTS
Exercise training led to a 27% increase in cytochrome c oxidase activity [from 21.8 (SE 3.2) to 27.7 (SE 3.5) nmol O2/mg per min, P=0.02 versus baseline]. Changes in iNOS expression and iNOS protein content were inversely correlated with changes in COX-activity (r=-0.60, P=0.01; r=-0.71, P<0.001).


CONCLUSIONS
The inverse correlation between iNOS expression/iNOS protein content and COX-activity indicates that local anti-inflammatory effects may contribute to improved muscular oxidative metabolism.
Gielen
Stephan
S
Universität Leipzig, Herzzentrum GmbH, Klinik für Innere Medizin/Kardiologie, Leipzig, Germany. hamr@medizin.uni-leipzig.de
Adams
Volker
V
Linke
Axel
A
Erbs
Sandra
S
Möbius-Winkler
Sven
S
Schubert
Andreas
A
Schuler
Gerhard
G
Hambrecht
Rainer
R
D000368:Aged; D002908:Chronic Disease; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism; D015444:Exercise; D005080:Exercise Test; D017079:Exercise Tolerance; D005500:Follow-Up Studies; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D018384:Oxidative Stress; D010101:Oxygen Consumption; D011446:Prospective Studies; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D003576:Electron Transport Complex IV