Netherlands Heart Journal

, Volume 21, Issue 2, pp 82–84 | Cite as

Vagal stimulation for heart diseases: from animals to men. An example of translational cardiology

Special Article
First Online:

Abstract

A significant series of experimental and clinical studies have demonstrated the close association between reduced vagal reflexes (baroreflex sensitivity, BRS) and increased sudden and non-sudden cardiovascular mortality. Subsequently, evidence was provided that, also among chronic heart failure (HF) patients, depressed BRS is associated with a poorer outcome. At the same time, the encouraging results with experimental and clinical attempts to increase cardiac vagal activity led to a few experimental studies with vagal stimulation (VS) in different models for HF. We first performed a pilot study for VS in HF patients, and then in 2011 we reported the results of a small size multicentre clinical trial. The 6-month and 1-year results are encouraging for feasibility, safety and appear to have a favourable clinical effect. An ongoing large clinical trial will provide a definitive assessment of the efficacy and usefulness of chronic VS in HF patients.

Keywords

Autonomic nervous system Baroreflex sensitivity Heart failure Vagal stimulation 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Schwartz PJ, De Ferrari GM. Sympathetic-parasympathetic interaction in health and disease: abnormalities and relevance in heart failure. Heart Fail Rev. 2011;16:101–7.PubMedCrossRefGoogle Scholar
  2. 2.
    De Ferrari GM, Schwartz PJ. Vagus nerve stimulation: from pre-clinical to clinical application: challenges and future directions. Heart Fail Rev. 2011;16:195–203.PubMedCrossRefGoogle Scholar
  3. 3.
    Schwartz PJ. Vagal stimulation for the treatment of heart failure: a translational success story. Heart. 2012;98:1687–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Malliani A, Schwartz PJ, Zanchetti A. A sympathetic reflex elicited by experimental coronary occlusion. Am J Physiol. 1969;217:703–9.PubMedGoogle Scholar
  5. 5.
    Schwartz PJ, Pagani M, Lombardi F, et al. A cardiocardiac sympatho-vagal reflex in the cat. Circ Res. 1973;32:215–20.PubMedCrossRefGoogle Scholar
  6. 6.
    Billman GE, Schwartz PJ, Stone HL. The effects of daily exercise on susceptibility to sudden cardiac death. Circulation. 1984;69:1182–9.PubMedCrossRefGoogle Scholar
  7. 7.
    La Rovere MT, Bigger Jr JT, Marcus FI, et al. For the ATRAMI Investigators: Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. Lancet. 1998;351:478–84.PubMedCrossRefGoogle Scholar
  8. 8.
    Levy MN, Schwartz PJ, editors. Vagal control of the heart: experimental basis and clinical implications. Armonk: Futura Publishing Co; 1994. p. 644.Google Scholar
  9. 9.
    Myers RW, Pearlman AS, Hyman RM, et al. Beneficial effect of vagal stimulation and bradycardia during experimental acute myocardial ischemia. Circulation. 1974;49:943–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Vanoli E, De Ferrari GM, Stramba-Badiale M, et al. Vagal stimulation and prevention of sudden death in conscious dogs with a healed myocardial infarction. Circ Res. 1991;68:1471–81.PubMedCrossRefGoogle Scholar
  11. 11.
    Mortara A, La Rovere MT, Pinna GD, et al. Arterial baroreflex modulation of heart rate in chronic heart failure: clinical and hemodynamic correlates and prognostic implications. Circulation. 1997;96:3450–8.PubMedCrossRefGoogle Scholar
  12. 12.
    La Rovere MT, Pinna GD, Maestri R, et al. Prognostic implications of baroreflex sensitivity in heart failure patients in the beta-blocking era. J Am Coll Cardiol. 2009;53:193–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Li M, Zheng C, Sato T, et al. Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation. 2004;109:120–4.PubMedCrossRefGoogle Scholar
  14. 14.
    Sabbah HN, Rastogi S, Mishra S, et al. Long-term therapy with neuroselective electric vagus nerve stimulation improves LV function and attenuates global LV remodelling in dogs with chronic heart failure. (abstr). Eur J Heart Fail. 2005;4(Suppl):166.Google Scholar
  15. 15.
    Sabbah HN, Imai M, Zaretsky A, et al. Therapy with vagus nerve electrical stimulation combined with beta-blockade improves left ventricular systolic function in dogs with heart failure beyond that seen with beta-blockade alone. (abstr). Eur J Heart Fail. 2007;6 Suppl 1:114.Google Scholar
  16. 16.
    Zhang Y, Popovic ZB, Bibevski S, et al. Chronic vagus nerve stimulation improves autonomic control and attenuates systemic inflammation and heart failure progression in a canine high-rate pacing model. Circ Heart Fail. 2009;2:692–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Schwartz PJ, De Ferrari GM, Sanzo A, et al. Long term vagal stimulation in patients with advanced heart failure: first experience in man. Eur J Heart Fail. 2008;10:884–91.PubMedCrossRefGoogle Scholar
  18. 18.
    De Ferrari GM, Crijns HJGM, Borggrefe M, et al. Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur Heart J. 2011;32:847–55.PubMedCrossRefGoogle Scholar
  19. 19.
    Tracey KJ. The inflammatory reflex. Nature. 2002;420:853–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Calvillo L, Vanoli E, Andreoli E, et al. Vagal stimulation, through its nicotinic action, limits infarct size and the inflammatory response to myocardial ischemia and reperfusion. J Cardiovasc Pharmacol. 2011;58:500–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Hauptman PJ, Schwartz PJ, Gold MR, et al. Rationale and study design of the increase of vagal tone in heart failure study: INOVATE-HF. Am Heart J. 2012;163:954–62.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Media / Bohn Stafleu van Loghum 2012

Authors and Affiliations

  1. 1.Department of Molecular MedicineUniversity of PaviaPaviaItaly
  2. 2.Department of CardiologyFondazione IRCCS Policlinico S. MatteoPaviaItaly
  3. 3.Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa, Department of MedicineUniversity of Cape TownCape TownSouth Africa
  4. 4.Department of Family and Community Medicine, College of MedicineKing Saud UniversityRiyadhSaudi Arabia

Personalised recommendations