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(Circulation. 1996;93:210-214.)
© 1996 American Heart Association, Inc.


Articles

Physical Training Improves Endothelial Function in Patients With Chronic Heart Failure

Burkhard Hornig, MD; Volker Maier, BS; Helmut Drexler, MD

From the Med Klinik III, University of Freiburg (Germany).

Correspondence to Helmut Drexler, MD, Med Klinik III, University of Freiburg, Hugstetterstr 55, 79106 Freiburg, Germany.

Background Chronic heart failure is associated with endothelial dysfunction including impaired endothelium-mediated, flow-dependent dilation (FDD). Since endothelial function is thought to play an important role in coordinating tissue perfusion and modulating arterial compliance, interventions to improve endothelial dysfunction are imperative.

Methods and Results To assess the potential of physical training to restore FDD, 12 patients with chronic heart failure were studied and compared with FDD of 7 age-matched normal subjects. With a recently developed high-resolution ultrasound system, diameters of radial artery were measured at rest, during reactive hyperemia (with increased flow causing endothelium-mediated dilation), and during sodium nitroprusside, causing endothelium-independent dilation. Determination of FDD was repeated after intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA, 7 µmol/min) to inhibit endothelial synthesis and release of nitric oxide. The protocol was performed at baseline, after 4 weeks of daily handgrip training, and 6 weeks after cessation of the training program. FDD was impaired in heart failure patients compared with normal subjects. L-NMMA attenuated FDD, indicating that the endothelial release of nitric oxide is involved in FDD. Physical training restored FDD in patients with heart failure. In particular, the portion of FDD inhibited by L-NMMA (representing FDD mediated by nitric oxide) was significantly higher after physical training (8-minute occlusion: 8.0±1% versus 5.4±0.9%; P<.05; normal subjects: 9.2±1%).

Conclusions These results indicate that physical training restores FDD in patients with chronic heart failure, possibly by enhanced endothelial release of nitric oxide.


Key Words: heart failure • endothelium • exercise • endothelium-derived factor




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J. Appl. Physiol.Home page
A. J. Maxwell, H.-K. V. Ho, C. Q. Le, P. S. Lin, D. Bernstein, and J. P. Cooke
L-Arginine enhances aerobic exercise capacity in association with augmented nitric oxide production
J Appl Physiol, March 1, 2001; 90(3): 933 - 938.
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CirculationHome page
B. Hornig, U. Landmesser, C. Kohler, D. Ahlersmann, S. Spiekermann, A. Christoph, H. Tatge, and H. Drexler
Comparative Effect of ACE Inhibition and Angiotensin II Type 1 Receptor Antagonism on Bioavailability of Nitric Oxide in Patients With Coronary Artery Disease : Role of Superoxide Dismutase
Circulation, February 13, 2001; 103(6): 799 - 805.
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J Am Coll CardiolHome page
A. Linke, N. Schoene, S. Gielen, J.u. Hofer, S. Erbs, G. Schuler, and R. Hambrecht
Endothelial dysfunction in patients with chronic heart failure: systemic effects of lower-limb exercise training
J. Am. Coll. Cardiol., February 1, 2001; 37(2): 392 - 397.
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Eur Heart JHome page
Recommendations for exercise training in chronic heart failure patients
Eur. Heart J., January 2, 2001; 22(2): 125 - 135.
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J Am Coll CardiolHome page
A. R. Patel, J. T. Kuvin, N. G. Pandian, J. J. Smith, J. E. Udelson, M. E. Mendelsohn, M. A. Konstam, and R. H. Karas
Heart failure etiology affects peripheral vascular endothelial function after cardiac transplantation
J. Am. Coll. Cardiol., January 1, 2001; 37(1): 195 - 200.
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J Am Coll CardiolHome page
Y. Ishibashi, T. Shimada, T. Sakane, N. Takahashi, T. Sugamori, S. Ohhata, S.-i. Inoue, H. Katoh, K. Sano, Y. Murakami, et al.
Contribution of endogenous nitric oxide to basal vasomotor tone of peripheral vessels and plasma B-Type natriuretic peptide levels in patients with congestive heart failure
J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1605 - 1611.
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Am. J. Physiol. Heart Circ. Physiol.Home page
A. Maiorana, G. O'Driscoll, L. Dembo, C. Cheetham, C. Goodman, R. Taylor, and D. Green
Effect of aerobic and resistance exercise training on vascular function in heart failure
Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1999 - H2005.
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FASEB J.Home page
B. A. KINGWELL
Nitric oxide-mediated metabolic regulation during exercise: effects of training in health and cardiovascular disease
FASEB J, September 1, 2000; 14(12): 1685 - 1696.
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CirculationHome page
R. Varin, P. Mulder, F. Tamion, V. Richard, J.-P. Henry, F. Lallemand, G. Lerebours, and C. Thuillez
Improvement of Endothelial Function by Chronic Angiotensin-Converting Enzyme Inhibition in Heart Failure : Role of Nitric Oxide, Prostanoids, Oxidant Stress, and Bradykinin
Circulation, July 18, 2000; 102(3): 351 - 356.
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CirculationHome page
S. Taddei, F. Galetta, A. Virdis, L. Ghiadoni, G. Salvetti, F. Franzoni, C. Giusti, and A. Salvetti
Physical Activity Prevents Age-Related Impairment in Nitric Oxide Availability in Elderly Athletes
Circulation, June 27, 2000; 101(25): 2896 - 2901.
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JAMAHome page
R. Hambrecht, S. Gielen, A. Linke, E. Fiehn, J. Yu, C. Walther, N. Schoene, and G. Schuler
Effects of Exercise Training on Left Ventricular Function and Peripheral Resistance in Patients With Chronic Heart Failure: A Randomized Trial
JAMA, June 21, 2000; 283(23): 3095 - 3101.
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CirculationHome page
U. Landmesser, R. Merten, S. Spiekermann, K. Buttner, H. Drexler, and B. Hornig
Vascular Extracellular Superoxide Dismutase Activity in Patients With Coronary Artery Disease : Relation to Endothelium-Dependent Vasodilation
Circulation, May 16, 2000; 101(19): 2264 - 2270.
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J Am Coll CardiolHome page
R. Hambrecht, L. Hilbrich, S. Erbs, S. Gielen, E. Fiehn, N. Schoene, and G. Schuler
Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation
J. Am. Coll. Cardiol., March 1, 2000; 35(3): 706 - 713.
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Arterioscler. Thromb. Vasc. Bio.Home page
A. Lavrencic, B. G. Salobir, and I. Keber
Physical Training Improves Flow-Mediated Dilation in Patients With the Polymetabolic Syndrome
Arterioscler Thromb Vasc Biol, February 1, 2000; 20(2): 551 - 555.
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Cardiovasc ResHome page
K. J. Osterziel, S. M Bode-Boger, O. Strohm, A. E Ellmer, N. Bit-Avragim, D. Hanlein, M. B Ranke, R. Dietz, and R. H Boger
Role of nitric oxide in the vasodilator effect of recombinant human growth hormone in patients with dilated cardiomyopathy
Cardiovasc Res, January 14, 2000; 45(2): 447 - 453.
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J. Appl. Physiol.Home page
D. P. Thomas and O. Hudlicka
Arteriolar reactivity and capillarization in chronically stimulated rat limb skeletal muscle post-MI
J Appl Physiol, December 1, 1999; 87(6): 2259 - 2265.
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Cardiovasc ResHome page
H. Drexler
Nitric oxide and coronary endothelial dysfunction in humans
Cardiovasc Res, August 15, 1999; 43(3): 572 - 579.
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CirculationHome page
R. Varin, P. Mulder, V. Richard, F. Tamion, C. Devaux, J.-P. Henry, F. Lallemand, G. Lerebours, and C. Thuillez
Exercise Improves Flow-Mediated Vasodilatation of Skeletal Muscle Arteries in Rats With Chronic Heart Failure : Role of Nitric Oxide, Prostanoids, and Oxidant Stress
Circulation, June 8, 1999; 99(22): 2951 - 2957.
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Eur Heart JHome page
R.P. Wielenga, I.A. Huisveld, E. Bol, P.H.J.M. Dunselman, R.A.M. Erdman, M.R.P. Baselier, and W.L. Mosterd
Safety and effects of physical training in chronic heart failure. Results of the Chronic Heart Failure and Graded Exercise study (CHANGE): (CHANGE)
Eur. Heart J., June 2, 1999; 20(12): 872 - 879.
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J Am Coll CardiolHome page
P. Clarkson, H. E. Montgomery, M. J. Mullen, A. E. Donald, A. J. Powe, T. Bull, M. Jubb, M. World, and J. E. Deanfield
Exercise training enhances endothelial function in young men
J. Am. Coll. Cardiol., April 1, 1999; 33(5): 1379 - 1385.
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ANGIOLOGYHome page
M. Krzanowski, A. Surdacki, R. Nizankowski, A. Szczeklik, J. S. Dubiel, and P. Petkow Dimitrow
Impaired Response of the Forearm Resistance but not Conductance Vessels to Reactive Hyperemia in Hypertrophic Cardiomyopathy
Angiology, April 1, 1999; 50(4): 267 - 272.
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Am. J. Physiol. Heart Circ. Physiol.Home page
J. Niebauer, A. J. Maxwell, P. S. Lin, P. S. Tsao, J. Kosek, D. Bernstein, and J. P. Cooke
Impaired aerobic capacity in hypercholesterolemic mice: partial reversal by exercise training
Am J Physiol Heart Circ Physiol, April 1, 1999; 276(4): H1346 - H1354.
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CirculationHome page
A. J. S. Coats
Exercise Training for Heart Failure : Coming of Age
Circulation, March 9, 1999; 99(9): 1138 - 1140.
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CirculationHome page
R. Belardinelli, D. Georgiou, G. Cianci, and A. Purcaro
Randomized, Controlled Trial of Long-Term Moderate Exercise Training in Chronic Heart Failure : Effects on Functional Capacity, Quality of Life, and Clinical Outcome
Circulation, March 9, 1999; 99(9): 1173 - 1182.
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J Am Coll CardiolHome page
W. Johnson, C. Lucas, L. W. Stevenson, and M. A. Creager
Effect of intensive therapy for heart failure on the vasodilator response to exercise
J. Am. Coll. Cardiol., March 1, 1999; 33(3): 743 - 749.
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CirculationHome page
M. B. Patel, I. V. Kaplan, R. N. Patni, D. Levy, J. A. Strom, J. Shirani, and T. H. LeJemtel
Sustained Improvement in Flow-Mediated Vasodilation After Short-Term Administration of Dobutamine in Patients With Severe Congestive Heart Failure
Circulation, January 12, 1999; 99(1): 60 - 64.
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HypertensionHome page
M. L. Muiesan, M. Salvetti, C. Monteduro, D. Rizzoni, R. Zulli, C. Corbellini, C. Brun, and E. Agabiti-Rosei
Effect of Treatment on Flow-Dependent Vasodilation of the Brachial Artery in Essential Hypertension
Hypertension, January 1, 1999; 33(1): 575 - 580.
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Cardiovasc ResHome page
J. Hansen, D. Sayad, G. D. Thomas, G. D. Clarke, R. M. Peshock, and R. G. Victor
Exercise-induced attenuation of alpha-adrenoceptor mediated vasoconstriction in humans: evidence from phase-contrast MRI
Cardiovasc Res, January 1, 1999; 41(1): 220 - 228.
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CirculationHome page
B. Hornig, N. Arakawa, D. Haussmann, and H. Drexler
Differential Effects of Quinaprilat and Enalaprilat on Endothelial Function of Conduit Arteries in Patients With Chronic Heart Failure
Circulation, December 22, 1998; 98(25): 2842 - 2848.
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CirculationHome page
H. Drexler
Endothelium as a Therapeutic Target in Heart Failure
Circulation, December 15, 1998; 98(24): 2652 - 2655.
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