Skip Navigation

European Heart Journal 1999 20(12):880-887; doi:10.1053/euhj.1998.1447
Copyright © 1999 by the European Society of Cardiology.
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (20)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Notarius, C.F.
Right arrow Articles by Floras, J.S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Notarius, C.F.
Right arrow Articles by Floras, J.S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Resting muscle sympathetic nerve activity and peak oxygen uptake in heart failure and normal subjects

C.F. Notarius, S. Ando, G.A. Rongen and J.S. Florasf1

Division of Cardiology and Harrowston Heart Failure Clinic, Mount Sinai Hospital
Division of Cardiology, The Toronto Hospital
The Centre for Cardiovascular Research, University of Toronto, Toronto, Ontario, Canada

revised November 24, 1998; accepted November 26, 1998

Abstract

Aims Exercise intolerance and increased efferent vasoconstrictor traffic to muscle are two characteristics of heart failure that have not been explicitly linked. We tested the hypothesis that peak oxygen consumption is inversely related to resting muscle sympathetic nerve activity in heart failure.

Methods and Results We recorded peroneal muscle sympathetic nerve activity in 17 treated heart failure patients (16 men,1 woman; mean ejection fraction of 26·0±3·2% (SE)) and 17 age-matched healthy subjects (16 men, 1 woman). Oxygen consumption was measured during cycle ergometry to maximal effort. In heart failure and normal subjects, mean peak oxygen consumption was 20·6±1·7 vs 32·2±2·6ml.kg–1.min–1(P<0·0001) and mean muscle sympathetic activity was 49·3±2·8 vs 33·0±3·3 bursts.min–1(P<·0007) respectively. When age was accounted for by multiple regression analysis, there was a significant relationship between peak oxygen consumption and burst frequency in heart failure (P<0·02) but not in healthy subjects. The percent of predicted peak oxygen consumption achieved (based on age, sex and body size) was inversely related to muscle sympathetic nerve burst frequency in heart failure (r=–0·71, P<0·0014) but not in normal subjects (r=–0·44, P<0·08;P<0·0001 for this comparison).

Conclusion Reduced exercise capacity in heart failure is related to increased efferent sympathetic traffic to calf muscle. These observations are consistent with the concept of a peripheral neurogenic limit to exercise in heart failure.

Key Words: Heart failure • oxygen consumption • sympathetic nerve activity • exercise capacity • ejection fraction

f1 Correspondence : John S. Floras, Division of Cardiology, Mount Sinai Hospital, Suite 1614, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada.

References

  1. Massie BM, Simonini A, Sahgal P, Wells L, Dudley GA. Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure. J Am Coll Cardiol. 1996;27:140–145[Abstract]
  2. Cowley AJ. Are breathlessness and fatigue in chronic heart failure due to the same pathophysiological abnormality? (Editorial). Eur Heart J. 1995;16:1–2[Free Full Text]
  3. Francis GS, Goldsmith SR, Cohn JN. Relationship of exercise capacity to resting left ventricular performance and basal plasma norepinephrine levels in patients with congestive heart failure. Am Heart J. 1982;4:725–731
  4. Kraemer MD, Kubo SH, Rector TS, Brunsvold N, Bank AJ. Pulmonary and peripheral vascular factors are important determinants of peak oxygen uptake in patients with heart failure. J Am Coll Cardiol. 1993;21:641–648[Abstract]
  5. Franciosa JA, Park M, Levine TB. Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure. Am J Cardiol. 1981;47:33–39[CrossRef][Web of Science][Medline]
  6. Cohn JN, Levine TB, Olivari MT. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311:819–823[Abstract]
  7. Stelken AM, Younis LT, Jennison SH. Prognostic value of cardiopulmonary exercise testing using percent achieved of predicted peak oxygen uptake for patients with ischemic and dilated cardiomyopathy. J Am Coll Cardiol. 1996;27:345–352[Abstract]
  8. Grassi G, Seravalle G, Cattaneo BM. Sympathetic activation and loss of reflex sympathetic control in mild congestive heart failure. Circulation. 1995;92:3206–3211[Abstract/Free Full Text]
  9. Francis GS, Benedict C, Johnstone DE. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A sub-study of the studies of left ventricular dysfunction (SOLVD). Circulation. 1990;82:1724–1729[Abstract/Free Full Text]
  10. Hasking GJ, Esler MD, Jennings GL, Burton D, Johns JA, Korner PI. Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation. 1986;73:615–621[Abstract/Free Full Text]
  11. Leimbach WN, Wallin BG, Victor RG, Aylward PE, Sundlof G, Mark AL. Direct evidence from intraneural recordings for increased central sympathetic outflow in patients with heart failure. Circulation. 1986;73:913–919[Abstract/Free Full Text]
  12. Hara K, Floras JS. After-effects of exercise on hemodynamics and sympathetic nerve activity in young subjects with dilated cardiomyopathy. Heart. 1996;75:602–608[Abstract/Free Full Text]
  13. Ferguson DW, Berg WJ, Sanders JS. Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings. J Am Coll Cardiol. 1990;16:1125–1134[Abstract]
  14. Naughton MT, Floras JS, Rahman MA, Jamal M, Bradley TD. Respiratory correlates of muscle sympathetic nerve activity in heart failure. Clin Sci. 1998;95:277–285[Medline]
  15. Joyner MJ, Nauss LA, Warner MA, Warner DO. Sympathetic modulation of blood flow and O2uptake in rhythmically contracting human forearm muscles. Am J Physiol. 1992;263:H1078–1083
  16. Lang CC, Rayos GH, Chomsky DB, Wood AJJ, Wilson JR. Effect of sympathoinhibition on exercise performance in patients with heart failure. Circulation. 1997;96:238–245[Abstract/Free Full Text]
  17. Shoemaker JK, Pandey P, Herr MD. Augmented sympathetic tone alters muscle metabolism with exercise: lack of evidence for functional sympatholysis. J Appl Physiol. 1997;82:1932–1938[Abstract/Free Full Text]
  18. Sinoway LI, Wilson JS, Zelis R. Sympathetic tone affects human limb vascular resistance during a maximal metabolic stimulus. Am J Physiol. 1988;255:H937–946
  19. Smith RF, Johnson G, Ziesche S, Bhat G, Blankenship K, Cohn JN. Functional capacity in heart failure: comparison of methods for assessment and their relation to other indexes of heart failure. Circulation. 1993;Suppl VI:VI-88–93
  20. Floras JS, Jones JV, Hassan MO, Osikowska BA, Sever PS, Sleight P. Failure of plasma norepinephrine to consistantly reflect sympathetic activity in humans. Hypertension. 1986;8:641–649[Abstract/Free Full Text]
  21. Floras JS. Sympathoinhibitory effects of atrial natriuretic factor in normal humans. Circulation. 1990;81:1860–1873[Abstract/Free Full Text]
  22. Rongen GA, Senn B, Ando S, Notarius CF, Stone J, Floras JS. Comparison of hemodynamic and sympathoneural responses to adenosine and lower body negative pressure in man. Can J Physiol Pharmacol. 1997;75:128–134[CrossRef][Web of Science][Medline]
  23. Jones NL, Makrides L, Hitchcock C, Chychar T, McCartney N. Normal standards for an incremental progressive cycle ergometer test. Am Rev Resp Dis. 1985;131:700–708[Web of Science][Medline]
  24. Hasking GL, Esler MD, Jennings GL, Dewar E, Lambert G. Norepinephrine spillover to plasma during steady-state supine bicycle exercise: comparison of patients with congestive heart failure and normal subjects. Circulation. 1988;78:516–521[Abstract/Free Full Text]
  25. O’Leary D, Robinson ED, Butler JL. Is active skeletal muscle functionally vasoconstricted during dynamic exercise in conscious dogs? Am J Physiol. 1997;272:R386–391
  26. Thompson LP, Mohrman DE. Blood flow and oxygen consumption in skeletal muscle during sympathetic stimulation. Am J Physiol. 1983;245:H66–71
  27. Buckwalter JB, Mueller PJ, Clifford PS. Sympathetic vasoconstriction in active skeletal muscles during dynamic exercise. J Appl Physiol. 1997;83:1575–1580[Abstract/Free Full Text]
  28. Rahman MA, Hara K, Daly PA, Floras JS. Reductions in muscle sympathetic nerve activity after long term metoprolol for dilated cardiomyopathy: preliminary observations. Br Heart J. 1995;74:431–436[Abstract/Free Full Text]
  29. Gradman A, Deedwania P, Cody R. Predictors of total mortality and sudden death in mild to moderate heart failure. Am J Cardiol. 1989;14:564–570
  30. Franciosa JA, Goldsmith SR, Cohn JN. Contrasting immediate and long-term effects of isosorbide dinitrate on exercise capacity in congestive heart failure. Am J Med. 1980;69:559–566[CrossRef][Web of Science][Medline]
  31. Volterrani M, Clark AL, Ludman PF. Predictors of exercise capacity in chronic heart failure. Eur Heart J. 1994;15:801–809[Abstract/Free Full Text]
  32. Ebert TJ, Morgan BJ, Barney JA, Denahan T, Smith JJ. The effects of aging on baroreflex regulation of sympathetic activity in humans. Am J Physiol. 1992;263:H798–803
  33. Seals DR. Sympathetic neural adjustments to stress in physically trained and untrained humans. Hypertension. 1991;17:36–43[Abstract/Free Full Text]
  34. Longhurst J, Gifford W, Zelis R. Impaired forearm oxygen consumption during static exercise in patients with congestive heart failure. Circulation. 1976;54:477–480[Abstract/Free Full Text]
  35. LeJemtel TH, Maskin CS, Lucido D, Chadwick BJ. Failure to augment maximal limb blood flow in response to one-leg vs two-leg exercise in patients with severe heart failure. Circulation. 1986;74:245–251[Abstract/Free Full Text]
  36. Sullivan MJ, Knight JD, Higgenbotham MB, Cobb FR. Relation between central and peripheral hemodynamics during exercise in patients with chronic heart failure: muscle blood flow is reduced with maintenance of arterial perfusion pressure. Circulation. 1989;80:769–781[Abstract/Free Full Text]
  37. Wilson JR, Martin JL, Schwartz D, Ferraro N. Exercise intolerance in patients with chronic heart failure: role of impaired nutritive flow to skeletal muscle. Circulation. 1984;69:1079–1087[Abstract/Free Full Text]
  38. Drexler H, Banhardt U, Meinertz T, Wollschlanger H, Lehmann M, Just H. Contrasting peripheral short-term and long-term effects of converting enzyme inhibition in patients with congestive heart failure. Circulation. 1989;79:491–502[Abstract/Free Full Text]
  39. Wilson JR, Frey AW, Mancini DM, Ferraro N, Jones R. Sympathetic vasoconstriction during exercise in ambulatory patients with left ventricular failure. Circulation. 1989;79:1021–1027[Abstract/Free Full Text]
  40. Lundberg JM, Martinnson A, Hemsen A. Co-release of neuropeptide Y and catecholamines during physical exercise in man. Biochem Biophys Res Comm. 1985;133:30–36[CrossRef][Web of Science][Medline]
  41. Burnstock G, Snedden P. Evidence for ATP and noradrenaline as cotransmitters in sympathetic nerves. Clin Sci. 1985;68:89S–92S
  42. Drexler H. Reduced exercise tolerance in chronic heart failure and its relationship to neurohumoral factors. Eur Heart J. 1991;12:21–28
  43. Sinoway LI, Minotti JR, Davis D. Delayed reversal of impaired vasodilation in congestive heart failure after heart transplantation. Am J Cardiol. 1988;61:1076–1079[CrossRef][Web of Science][Medline]
  44. Rundqvist B, Elam M, Eisenhofer G, Friberg P. Normalization of total body and regional sympathetic hyperactivity in heart failure after transplantation. J Heart Lung Transplant. 1996;15:516–526[Web of Science][Medline]
  45. Shemesh J, Grossman E, Peleg E, Steinmetz A, Rosenthal T, Motro M. Norepinephrine and atrial natriuretic peptide responses to exercise testing in rehabilitated and nonrehabilitated men with ischemic cardiomyopathy after healing of anterior wall acute myocardial infarction. Am J Cardiol. 1995;75:1072–1074[CrossRef][Web of Science][Medline]
  46. Coats AJS, Adamopoulos S, Radaelli A. Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function. Circulation. 1992;85:2119–2131[Abstract/Free Full Text]
  47. Anderssen B, Blomstrom-Lundqvist C, Hedner T, Waagstein F. Exercise hemodynamics and myocardial metabolism during long-term beta-adrenergic blockade in severe heart failure. J Am Coll Cardiol. 1991;18:1059–1066[Abstract]
  48. Jessup M. Beta-adrenergic blockade in congestive heart failure: answering the old questions. Editorial Comment. J Am Coll Cardiol. 1991;18:1067–1069[Web of Science][Medline]
  49. Kinugawa T, Ogino K, Kitamura H. Catecholamines, renin–angiotensin–aldosterone system, and atrial natriuretic peptide at rest and during submaximal exercise in patients with congestive heart failure. Am J Med Sci. 1996;312:110–117[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. F. Notarius, B. L. Morris, and J. S. Floras
Dissociation between reflex sympathetic and forearm vascular responses to lower body negative pressure in heart failure patients with coronary artery disease
Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1760 - H1766.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
J. S. Floras
Sympathetic nervous system activation in human heart failure: clinical implications of an updated model.
J. Am. Coll. Cardiol., July 28, 2009; 54(5): 375 - 385.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
H. Murai, M. Takamura, M. Maruyama, M. Nakano, T. Ikeda, D. Kobayashi, K.-i. Otowa, H. Ootsuji, M. Okajima, H. Furusho, et al.
Altered firing pattern of single-unit muscle sympathetic nerve activity during handgrip exercise in chronic heart failure
J. Physiol., June 1, 2009; 587(11): 2613 - 2622.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
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]

Home page
 HypertensionHome page
J. Spaak, Z. J. Egri, T. Kubo, E. Yu, S.-I. Ando, Y. Kaneko, K. Usui, T. D. Bradley, and J. S. Floras
Muscle Sympathetic Nerve Activity During Wakefulness in Heart Failure Patients With and Without Sleep Apnea
Hypertension, December 1, 2005; 46(6): 1327 - 1332.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
D. W. Wray, P. J. Fadel, M. L. Smith, P. Raven, and M. Sander
Inhibition of {alpha}-adrenergic vasoconstriction in exercising human thigh muscles
J. Physiol., March 1, 2004; 555(2): 545 - 563.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Heart FailHome page
A. Radzewitz, E. Miche, G. Herrmann, M. Nowak, U. Montanus, U. Adam, Y. Stockmann, and M. Barth
Exercise and muscle strength training and their effect on quality of life in patients with chronic heart failure
Eur J Heart Fail, October 1, 2002; 4(5): 627 - 634.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
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]

Home page
 Eur J Heart FailHome page
P. A.R. de Milliano, B. L.F. van Eck-Smit, P. A. van Zwieten, A. C. de Groot, J. G.P. Tijssen, and K. I. Lie
Relationship between cardiac metaiodobenzylguanidine uptake and hemodynamic, functional and neurohormonal parameters in patients with heart failure
Eur J Heart Fail, December 1, 2001; 3(6): 693 - 697.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
T. Kubo, E. R. Azevedo, G. E. Newton, J. D. Parker, and J. S. Floras
Lack of evidence for peripheral alpha1- adrenoceptor blockade during long-term treatment of heart failure with carvedilol
J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1463 - 1469.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. F. Notarius, D. J. Atchison, G. A. Rongen, and J. S. Floras
Effect of adenosine receptor blockade with caffeine on sympathetic response to handgrip exercise in heart failure
Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1312 - H1318.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. F. Notarius, D. J. Atchison, and J. S. Floras
Impact of heart failure and exercise capacity on sympathetic response to handgrip exercise
Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H969 - H976.
[Abstract] [Full Text] [PDF]

Home page
 EuropaceHome page
C. F. Notarius and J. S. Floras
Limitations of the use of spectral analysis of heart rate variability for the estimation of cardiac sympathetic activity in heart failure
Europace, January 1, 2001; 3(1): 29 - 38.
[Abstract] [PDF]

Home page
 QJMHome page
C.H. Davies and Y. Bashir
Beta-blockers for heart failure-time to think the unthinkable?
QJM, November 1, 1999; 92(11): 673 - 678.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (20)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Notarius, C.F.
Right arrow Articles by Floras, J.S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Notarius, C.F.
Right arrow Articles by Floras, J.S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?