CLINICAL STUDY
Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure
Stephan Gielen, MD*,
Volker Adams, PhD*,
Sven Möbius-Winkler, MD*,
Axel Linke, MD*,
Sandra Erbs, MD*,
Jiangtao Yu, MD*,
Werner Kempf, MD ,
Andreas Schubert, PhD ,
Gerhard Schuler, MD* and
Rainer Hambrecht, MD*,*
* Universität Leipzig, Herzzentrum GmbH, Klinik für Innere Medizin/Kardiologie, Leipzig, Germany
Klinik für Herzchirurgie, Leipzig, Germany
Universitätsspital Zürich, Dept. für Dermatologie, Zürich, Switzerland
Manuscript received January 16, 2003;
revised manuscript received March 12, 2003,
accepted March 20, 2003.
* Reprint requests and correspondence: Prof. Dr. med. R. Hambrecht, Universität Leipzig, Herzzentrum GmbH, Department of Internal Medicine/Cardiology, Strümpellstr. 39, 04289, Leipzig, Germany.
hamr{at}medizin.uni-leipzig.de
OBJECTIVES: The aim of this study was to assess the effects of regular physical exercise on local inflammatory parameters in the skeletal muscle of patients with chronic heart failure (CHF).
BACKGROUND: Inflammatory activation with increased serum cytokine levels and expression of inducible nitric oxide synthase (iNOS) in the myocardium and peripheral skeletal muscles has been described in CHF.
METHODS: Twenty male patients with stable CHF (left ventricular ejection fraction 25 ± 2%; age 54 ± 2 years) were randomized to a training group (n = 10) or a control group (n = 10). At baseline and after six months, serum samples and vastus lateralis muscle biopsies were obtained. Serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1-beta levels were measured by enzyme-linked immunosorbent assay, local cytokine, and iNOS expression by real-time polymerase chain reaction.
RESULTS: Exercise training improved peak oxygen uptake by 29% in the training group (from 20.3 ± 1.0 to 26.1 ± 1.5 ml/kg · min; p < 0.001 vs. control group). While serum levels of TNF-alpha, IL-6, and IL-1-beta remained unaffected by training, local skeletal muscle TNF-alpha decreased from 1.9 ± 0.4 to 1.2 ± 0.3 relative U (p < 0.05 for change vs. control group), IL-6 from 71.3 ± 16.5 to 41.3 ± 8.8 relative U (p < 0.05 vs. begin), and IL-1-beta from 2.7 ± 1.1 to 1.4 ± 0.6 relative U (p = 0.02 vs. control group). Exercise training also reduced local iNOS expression by 52% (from 6.3 ± 1.2 to 3.0 ± 1.0 relative U; p = 0.007 vs. control group).
CONCLUSIONS: Exercise training significantly reduced the local expression of TNF-alpha, IL-1-beta, IL-6, and iNOS in the skeletal muscle of CHF patients. These local anti-inflammatory effects of exercise may attenuate the catabolic wasting process associated with the progression of CHF.
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Abbreviations and Acronyms
| | cDNA | | complementary deoxyribonucleic acid | | CHF | | chronic heart failure | | COX | | cytochrome c oxidase | | iNOS | | inducible nitric oxide synthase | | IL | | interleukin | | mRNA | | messenger ribonucleic acid | | NYHA | | New York Heart Association | | ROS | | reactive oxygen species | | rRNA | | ribosomal ribonucleic acid | | TNF | | tumor necrosis factor | | VO2max | | maximal oxygen uptake |
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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659 - 671.
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|
|
|
|
|
|
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I. Vogiatzis, G. Stratakos, D. C M Simoes, G. Terzis, O. Georgiadou, C. Roussos, and S. Zakynthinos
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|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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29(3):
246 - 252.
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|
|
|
|
|
|
|
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May 1, 2007;
1(3):
220 - 235.
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[PDF]
|
|
|
|
|
|
|
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102(5):
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|
|
|
|
|
|
|
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January 1, 2007;
73(1):
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|
|
|
|
|
|
|
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December 1, 2006;
8(8):
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|
|
|
|
|
|
|
J. M. Lawler, H.-B. Kwak, W. Song, and J. L. Parker
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291(6):
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|
|
|
|
|
|
|
D. Mereles, N. Ehlken, S. Kreuscher, S. Ghofrani, M. M. Hoeper, M. Halank, F. J. Meyer, G. Karger, J. Buss, J. Juenger, et al.
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114(14):
1482 - 1489.
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|
|
|
|
|
|
|
S. Jelic and T. H. Le Jemtel
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130(4):
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|
|
|
|
|
|
|
S. S. Gottlieb and I. L. Pina
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J. Am. Coll. Cardiol.,
September 19, 2006;
48(6):
1206 - 1207.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. K. McFarlin, M. G. Flynn, W. W. Campbell, B. A. Craig, J. P. Robinson, L. K. Stewart, K. L. Timmerman, and P. M. Coen
Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4.
J. Gerontol. A Biol. Sci. Med. Sci.,
April 1, 2006;
61(4):
388 - 393.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kalani, S. Judge, C. Carter, M. Pahor, and C. Leeuwenburgh
Effects of Caloric Restriction and Exercise on Age-Related, Chronic Inflammation Assessed by C-Reactive Protein and Interleukin-6.
J. Gerontol. A Biol. Sci. Med. Sci.,
March 1, 2006;
61(3):
211 - 217.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Toth, P. A. Ades, M. M. LeWinter, R. P. Tracy, and A. Tchernof
Skeletal muscle myofibrillar mRNA expression in heart failure: relationship to local and circulating hormones
J Appl Physiol,
January 1, 2006;
100(1):
35 - 41.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Bruunsgaard
Physical activity and modulation of systemic low-level inflammation
J. Leukoc. Biol.,
October 1, 2005;
78(4):
819 - 835.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Schiotz Thorud, A. Stranda, J.-A. Birkeland, P. K. Lunde, I. Sjaastad, S. O. Kolset, O. M. Sejersted, and P. O. Iversen
Enhanced matrix metalloproteinase activity in skeletal muscles of rats with congestive heart failure
Am J Physiol Regulatory Integrative Comp Physiol,
August 1, 2005;
289(2):
R389 - R394.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Kasapis and P. D. Thompson
The Effects of Physical Activity on Serum C-Reactive Protein and Inflammatory Markers: A Systematic Review
J. Am. Coll. Cardiol.,
May 17, 2005;
45(10):
1563 - 1569.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Nicklas, T. You, and M. Pahor
Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training
Can. Med. Assoc. J.,
April 26, 2005;
172(9):
1199 - 1209.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Linke, V. Adams, P. C. Schulze, S. Erbs, S. Gielen, E. Fiehn, S. Mobius-Winkler, A. Schubert, G. Schuler, and R. Hambrecht
Antioxidative Effects of Exercise Training in Patients With Chronic Heart Failure: Increase in Radical Scavenger Enzyme Activity in Skeletal Muscle
Circulation,
April 12, 2005;
111(14):
1763 - 1770.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Niebauer, A. L. Clark, K. M. Webb-Peploe, and A. J.S. Coats
Exercise training in chronic heart failure: effects on pro-inflammatory markers
Eur J Heart Fail,
March 2, 2005;
7(2):
189 - 193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Valgimigli, C. Ceconi, P. Malagutti, E. Merli, O. Soukhomovskaia, G. Francolini, G. Cicchitelli, A. Olivares, G. Parrinello, G. Percoco, et al.
Tumor Necrosis Factor-{alpha} Receptor 1 Is a Major Predictor of Mortality and New-Onset Heart Failure in Patients With Acute Myocardial Infarction: The Cytokine-Activation and Long-Term Prognosis in Myocardial Infarction (C-ALPHA) Study
Circulation,
February 22, 2005;
111(7):
863 - 870.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. P. Fischer, P. Plomgaard, A. K. Hansen, H. Pilegaard, B. Saltin, and B. K. Pedersen
Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle
Am J Physiol Endocrinol Metab,
December 1, 2004;
287(6):
E1189 - E1194.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Pilon, P. Dallaire, and A. Marette
Inhibition of Inducible Nitric-oxide Synthase by Activators of AMP-activated Protein Kinase: A NEW MECHANISM OF ACTION OF INSULIN-SENSITIZING DRUGS
J. Biol. Chem.,
May 14, 2004;
279(20):
20767 - 20774.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Larsen and K. Dickstein
Can sedentary patients with heart failure achieve the beneficial effect of exercise training without moving?
Eur. Heart J.,
January 2, 2004;
25(2):
104 - 106.
[Full Text]
[PDF]
|
|
|
|
