(Circulation. 1997;96:238-245.)
© 1997 American Heart Association, Inc.
Articles |
Effect of Sympathoinhibition on Exercise Performance in Patients With Heart Failure
From the Division of Cardiology and Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tenn.
Correspondence to John R. Wilson, MD, Division of Cardiology, 315 MRB II, Vanderbilt University Medical Center, Nashville, TN 37232.
Background In patients with heart failure, excessive sympathetic activation during exercise could interfere with exercise performance by impairing arteriolar dilation in working muscle and by adversely altering skeletal muscle metabolic behavior. To test this hypothesis, we examined the effect of sympathoinhibition with clonidine, a central sympatholytic agent, on skeletal muscle blood flow and metabolism in patients with heart failure.
Methods and Results Swan-Ganz and femoral venous catheters
were inserted in 20 patients with chronic heart failure and exercise
intolerance (peak exercise 
O2=9.3±1.4
[SEM]
mL·min-1·kg-1).
Central hemodynamic measurements, leg blood flow
determined by thermodilution, and systemic and leg
metabolic parameters were measured during
maximal treadmill exercise before and 2 hours after clonidine 2 µg/kg
IV (n=15) or 0.9% normal saline (n=5). During control exercise before
the administration of clonidine, leg blood flow increased from 0.3±0.1
to 1.8±0.2 L/min and plasma norepinephrine increased from
485±61 to 2155±186 pg/mL (both P<.01). Treatment with
clonidine markedly suppressed norepinephrine levels during
exercise (matched peak exercise workload: control, 2137±187 versus
clonidine, 1430±161 pg/mL), increased leg blood flow (control,
1.8±0.2 versus clonidine, 2.3±0.4 L/min), reduced systemic oxygen
consumption (control, 1002±70 versus clonidine, 966±68 mL/min),
reduced pulmonary artery lactate concentration (control,
3.2±0.3 versus clonidine, 2.6±0.2 mEq/L), and decreased minute
ventilation (control, 39.7±2.1 versus clonidine, 34.9±2.4 L/min) (all
P<.05).
Conclusions These findings suggest that sympathetic activation during exercise reduces leg blood flow, increases muscle glycolysis, and decreases muscle efficiency in patients with heart failure.
Key Words: heart failure • catecholamines • clonidine • regional blood flow • exercise • muscles
This article has been cited by other articles:
 |
|
 |
|
  F. Triposkiadis, G. Karayannis, G. Giamouzis, J. Skoularigis, G. Louridas, and J. Butler The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications. J. Am. Coll. Cardiol., November 3, 2009; 54(19): 1747 - 1762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. N. Bacurau, M. A. Jardim, J. C. B. Ferreira, L. R. G. Bechara, C. R. Bueno Jr., T. C. Alba-Loureiro, C. E. Negrao, D. E. Casarini, R. Curi, P. R. Ramires, et al. Sympathetic hyperactivity differentially affects skeletal muscle mass in developing heart failure: role of exercise training J Appl Physiol, May 1, 2009; 106(5): 1631 - 1640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Kirby, W. F. Voyles, R. E. Carlson, and F. A. Dinenno Graded sympatholytic effect of exogenous ATP on postjunctional {alpha}-adrenergic vasoconstriction in the human forearm: implications for vascular control in contracting muscle J. Physiol., September 1, 2008; 586(17): 4305 - 4316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Vittorio, R. Zolty, M. E. Kasper, R. M. Khandwalla, D. S. Hirsh, C.-H. Tseng, U. P. Jorde, and K. Ahuja Differential Effects of Carvedilol and Metoprolol Succinate on Plasma Norepinephrine Release and Peak Exercise Heart Rate in Subjects With Chronic Heart Failure Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2008; 13(1): 51 - 57. [Abstract] [PDF]
|
|
|
|
|
|
C. Lundby, R. Boushel, P. Robach, K. Moller, B. Saltin, and J. A. L. Calbet During hypoxic exercise some vasoconstriction is needed to match O2 delivery with O2 demand at the microcirculatory level J. Physiol., January 1, 2008; 586(1): 123 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Smith, W. F. Voyles, B. S. Kirby, R. R. Markwald, and F. A. Dinenno Ageing and leg postjunctional {alpha}-adrenergic vasoconstrictor responsiveness in healthy men J. Physiol., July 1, 2007; 582(1): 63 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Levy, B. A. Maichel, N. P. Steele, K. M. Leclerc, and J. R. Stratton Biomechanical efficiency is decreased in heart failure during low-level steady state and maximal ramp exercise Eur J Heart Fail, December 1, 2004; 6(7): 917 - 926. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Dinenno and M. J. Joyner Combined NO and PG inhibition augments {alpha}-adrenergic vasoconstriction in contracting human skeletal muscle Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2576 - H2584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Aggarwal, M. D. Esler, M. J. Morris, G. Lambert, and D. M. Kaye Regional Sympathetic Effects of Low-Dose Clonidine in Heart Failure Hypertension, March 1, 2003; 41(3): 553 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.M. Kaye Alterations in oxygen consumption and sympathetic nervous activity in heart failure: independent or associated mechanisms? Eur. Heart J., May 2, 2002; 23(10): 764 - 766. [Full Text] [PDF]
|
|
|
|
|
|
C.F. Notarius, E.R. Azevedo, J.D. Parker, and J.S. Floras Peak oxygen uptake is not determined by cardiac noradrenaline spillover in heart failure Eur. Heart J., May 2, 2002; 23(10): 800 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shite, E. Dong, H. Kawai, S. Y. Stevens, and C.-S. Liang Selegiline improves cardiac sympathetic terminal function and beta -adrenergic responsiveness in heart failure Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1283 - H1290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kardos, D. J. Taylor, C. Thompson, P. Styles, L. Hands, J. Collin, and B. Casadei Sympathetic Denervation of the Upper Limb Improves Forearm Exercise Performance and Skeletal Muscle Bioenergetics Circulation, June 13, 2000; 101(23): 2716 - 2720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Gavras, A. J. Manolis, and H. Gavras The Economics of Therapeutic Advances: The Paradigm of Sympathetic Suppression in Chronic Heart Failure Arch Intern Med, December 13, 1999; 159(22): 2634 - 2636. [Full Text] [PDF]
|
|
|
|
|
|
C.F. Notarius, S. Ando, G.A. Rongen, and J.S. Floras Resting muscle sympathetic nerve activity and peak oxygen uptake in heart failure and normal subjects Eur. Heart J., June 2, 1999; 20(12): 880 - 887. [Abstract] [PDF]
|
|
|
|
|
|
E. R. Azevedo, G. E. Newton, and J. D. Parker Cardiac and systemic sympathetic activity in response to clonidine in human heart failure J. Am. Coll. Cardiol., January 1, 1999; 33(1): 186 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Hasenfuss Animal models of human cardiovascular disease, heart failure and hypertrophy Cardiovasc Res, July 1, 1998; 39(1): 60 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Thomas, W. Zhang, and R. G. Victor Impaired Modulation of Sympathetic Vasoconstriction in Contracting Skeletal Muscle of Rats With Chronic Myocardial Infarctions : Role of Oxidative Stress Circ. Res., April 27, 2001; 88(8): 816 - 823. [Abstract] [Full Text] [PDF]
|
|