Skip to main content

Advertisement

Log in

Pharmacologic modulation of parasympathetic activity in heart failure

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

In the congestive heart failure state, autonomic dysregulation involves an increase in sympathetic tone and decrease in parasympathetic tone and is associated with increased mortality. It is possible that augmentation of the parasympathetic nervous system (PNS) with pharmacologic therapy may lead to improved symptoms and/or clinical outcomes. There are several new and established pharmacologic interventions that have been studied for their effect on the PNS, including antagonists of the renin–angiotensin system, beta-adrenergic antagonists, digoxin, and vasodilators. In this review, we discuss the current status of the published literature on pharmacologic influences on the PNS by both conventional and experimental drugs targeting heart failure as well as drugs that more directly influence vagal tone. While these analyses have been largely limited to putative surrogates for clinical outcomes like heart rate variability, and it is often difficult to differentiate between indirect and direct pharmacologic effects on the PNS, significant insight into potential mechanisms of action can be derived. The future evaluation of drugs in development for heart failure treatment should include a careful, scientifically sound exploration of the potential impact of the intervention on PNS activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Olshansky B, Sabbah N, Hauptman PJ, Colucci WS (2008) The parasympathetic nervous system and heart failure: pathophysiology and implications for therapy. Circulation 118:863–871

    Article  PubMed  Google Scholar 

  2. Schwartz PJ, De Ferrari GM, Sanzo A, Landolina M, Rordorf R, Raineri C, Campana C, Revera M, Ajmone-Marsan N, Tavazzi L, Odero A (2008) Long term vagal stimulation in patients with advanced heart failure: first experience in man. Eur J Heart Fail 10:884–891

    Article  PubMed  Google Scholar 

  3. Osterziel K, Dietz R (1996) Improvement of vagal tone by ACE inhibition: a mechanism of cardioprotection in patients with mild-to-moderate heart failure. J Cardiovasc Pharmacol 27(2):25–30

    Article  Google Scholar 

  4. Osterziel K, Rohrig N, Dietz R, Manthey J, Hecht J, Kubler W (1988) Influence of captopril on the arterial baroreceptor reflex in patients with heart failure. Eur Heart J 9:1137–1145

    CAS  PubMed  Google Scholar 

  5. Task Force of the European Society of Cardiology and the North American Society of Pacing Electrophysiology (1996) Heart rate variability: standards of measurement, physiological interpretation, and clinical use. Circulation 93:1043–1065

    Google Scholar 

  6. Miyashita Y, Furukawa Y, Nakajima K, Hirose M, Kurogouchi F, Chiba S (1999) Parasympathetic inhibition of sympathetic effects on pacemaker location and rate in hearts of anesthetized dogs. J Cardiovasc Electrophysiol 10(8):1066–1076

    Article  CAS  PubMed  Google Scholar 

  7. Colucci WS (1990) In vivo studies of myocardial beta-adrenergic receptor pharmacology in patients with congestive heart failure. Circulation 82(2 Suppl):I44–I51

    CAS  PubMed  Google Scholar 

  8. Khamssi M, Brodde OE (1990) The role of cardiac beta1- and beta2-adrenoceptor stimulation in heart failure. J Cardiovasc Pharmacol 16(Suppl 5):S133–S137

    PubMed  Google Scholar 

  9. Janse MJ (2004) Electrophysiological changes in heart failure and their relationship to arrhythmogenesis. Cardiovasc Res 61(2):208–217

    Article  CAS  PubMed  Google Scholar 

  10. Palatini P (2001) Heart rate as a cardiovascular risk factor: do women differ from men? Ann Med 33(4):213–221

    Article  CAS  PubMed  Google Scholar 

  11. Hjalmarson A (1998) Significance of reduction in heart rate in cardiovascular disease. Clin Cardiol 21(12 Suppl 2):II3–II7

    CAS  PubMed  Google Scholar 

  12. Brown MD, Davies MK, Hudlicka O (2005) Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia. Angiogenesis 8(3):253–262. Epub 2005 Nov 25

    Google Scholar 

  13. Flannery G, Gehrig-Mills R, Billah B, Krum H (2008) Analysis of randomized controlled trials on the effect of magnitude of heart rate reduction on clinical outcomes in patients with systolic chronic heart failure receiving beta-blockers. Am J Cardiol 101(6):865–869. Epub 2008 Feb 21

    Google Scholar 

  14. Alboni P, Scarfò S, Fucà G (2001) Development of heart failure in bradycardic sick sinus syndrome. Ital Heart J 2(1):9–12

    CAS  PubMed  Google Scholar 

  15. Wolf MM, Varigos GA, Hunt D, Sloman JG (1978) Sinus arrhythmia in acute myocardial infarction. Med J Aust 2(2):52–53

    CAS  PubMed  Google Scholar 

  16. Akselrod S, Gordon D, Ubel FA, Shannon DC, Barger AC, Cohen RJ (1981) Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat to beat cardiovascular control. Science 213:220–222

    Article  CAS  PubMed  Google Scholar 

  17. Coumel P, Maison-Blanche P, Catuli D et al (1994) Heart rate and heart rate variability in normal young adults. J Cardiovasc Electrophysiol 5:899–911

    Article  CAS  PubMed  Google Scholar 

  18. Malik M (2004) Standard measurement of heart rate variability in dynamic electrocardiography. In: Malik M, Camm AJ (eds) Dynamic electrocardiography. Blackwell Futura, Malden, MA

    Chapter  Google Scholar 

  19. Guzik P, Piskorski J, Krauze T, Schneider R, Wesseling KH, Wykretowicz A, Wysocki H (2007) Correlations between the Poincaré plot and conventional heart rate variability parameters assessed during paced breathing. J Physiol Sci 57(1):63–71

    Article  PubMed  Google Scholar 

  20. Pagani M, Lombardi F, Guzzetti S et al (1986) Power spectral analysis of heart rate and arterial pressure variabilities as a marker of smypatho-vagal interaction in man and conscious dog. Circ Res 59:178–193

    CAS  PubMed  Google Scholar 

  21. Steptoe A, Vögele C (1990) Cardiac baroreflex function during postural change assessed using non-invasive spontaneous sequence analysis in young men. Cardiovasc Res 24(8):627–632

    Article  CAS  PubMed  Google Scholar 

  22. Frankel RA, Metting PJ, Britton SL (1993) Evaluation of spontaneous baroreflex sensitivity in conscious dogs. J Physiol 462:31–45

    CAS  PubMed  Google Scholar 

  23. Ducher M, Fauvel JP, Gustin MP, Cerutti C, Najem R, Cuisinaud G, Laville M, Pozet N, Paultre CZ (1995) A new non-invasive statistical method to assess the spontaneous cardiac baroreflex in humans. Clin Sci (Lond) 88(6):651–655

    CAS  Google Scholar 

  24. Watanabe MA, Schmidt G (2004) Heart rate turbulence: a 5-year review. Heart Rhythm 6:732–738

    Article  Google Scholar 

  25. Schmidt G, Malik M, Barthel P, Schneider R, Ulm K, Rolnitzky L, Camm JA, Bigger JT Jr, Schömig A (1999) Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction. Lancet 353:1390–1396

    Article  CAS  PubMed  Google Scholar 

  26. Ghuran A, Reid F, La Rovere MT, Schmidt G, Bigger JT Jr, Camm AJ, Schwartz PJ, Malik M (2002) ATRAMI Investigators. Heart rate turbulence-based predictors of fatal and nonfatal cardiac arrest (The autonomic tone and reflexes after myocardial infarction substudy). Am J Cardiol 89:184–190

    Article  PubMed  Google Scholar 

  27. Barthel P, Schneider R, Bauer A, Ulm K, Schmitt C, Schömig A, Schmidt G (2003) Risk stratification after acute myocardial infarction by heart rate turbulence. Circulation 108(10):1221–1226. Epub 2003 Aug 25

    Google Scholar 

  28. Sade E, Aytemir K, Oto A, Nazli N, Ozmen F, Ozkutlu H, Tokgözoglu L, Aksöyek S, Ovünç K, Kabakçi G, Ozer N, Kes S (2003) Assessment of heart rate turbulence in the acute phase of myocardial infarction for long-term prognosis. Pacing Clin Electrophysiol 26(2 Pt 1):544–550

    Article  PubMed  Google Scholar 

  29. Flapan A, Nolan J, Neilson J, Ewing D (1992) Effect of captopril on cardiac parasympathetic activity in chronic cardiac failure secondary to coronary artery disease. Am J Cardiol 69:532–535

    Article  CAS  PubMed  Google Scholar 

  30. Binkley P, Haas G, Starling R, Nunziata E, Hatton P, Leier C, Cody R (1993) Sustained augmentation of parasympathetic tone with angiotensin-converting enzyme inhibition in patients with congestive heart failure. JACC 21(3):655–661

    CAS  PubMed  Google Scholar 

  31. Zhang Y, Song Y, Jun Z, Tao-hong H, Li-li W (1995) Effects of enalapril on heart rate variability in patients with congestive heart failure. Am J Cardiol 76:1045–1048

    Article  CAS  PubMed  Google Scholar 

  32. Guedon-Moreau L, Pinaud A, Logier R, Caron J, Lekieffre J, Dupuis B, Libersa C (1997) Effect of ramipril on heart rate variability in digitalis-treated patients with chronic heart failure. Cardiovasc Drugs Ther 11:531–536

    Article  CAS  PubMed  Google Scholar 

  33. Kamen P, Krum H, Tonkin A (1997) Low-dose but not high-dose captopril increases parasympathetic activity in patients with heart failure. J Cardiovasc Pharmacol 30(1):7–11

    Article  CAS  PubMed  Google Scholar 

  34. Adigun A, Asiyanbola B, Ajayi A (2001) Cardiac autonomic function in blacks with congestive heart failure: vagomimetic action, alteration in sympathovagal balance, and the effect of ACE inhibition on central and peripheral vagal tone. Cell Mol Biol 47(6):1063–1066

    CAS  PubMed  Google Scholar 

  35. Ondocin P, Narsipur S (2006) Influence of angiotensin converting enzyme inhibitor treatment on cardiac autonomic modulation in patients receiving haemodialysis. Nephrology 11:497–501

    Article  CAS  PubMed  Google Scholar 

  36. Dibona G, Jones S, Sawin L (1998) Angiotensin receptor antagonist improves cardiac reflex control of renal sodium handling in heart failure. Am J Physiol Heart Circ Physiol 274:636–641

    Google Scholar 

  37. Tambara K, Fujita M, Sumita Y, Miyamoto S, Sekiguchi H, Eiho S, Komeda M (2004) Beneficial effect of candesartan treatment on cardiac autonomic nervous activity in patients with chronic heart failure: simultaneous recording of ambulatory electrocardiogram and posture. Clin Cardiol 27:300–303

    Article  PubMed  Google Scholar 

  38. Petretta M, Spinelli L, Marciano F, Apicella C, Vicario M, Testa G, Volpe M, Bonaduce D (2000) Effects of losartan treatment on cardiac autonomic control during volume loading in patients with DCM. Am J Physiol Heart Circ Physiol 279:86–92

    Google Scholar 

  39. Ozdemir M, Arslan U, Turkoglu S, Balcioglu S, Cengel A (2007) Losartan improves heart rate variability and heart rate turbulence in heart failure due to ischemic cardiomyopathy. J Cardiac Fail 13:812–817

    Article  CAS  Google Scholar 

  40. Vaile J, Chowdhary S, Osman F, Ross H, Fletcher J, Littler W, Coote J, Townend J (2001) Effects of angiotensin II (AT1) receptor blockade on cardiac vagal control in heart failure. Clin Sci 101:559–566

    Article  CAS  PubMed  Google Scholar 

  41. De Tommasi E, Iacoviello M, Romito R, Ceconi C, Guida P, Massari F, Francolini G, Bertocchi F, Ferrari R, Rizzon P, Pitzalis M (2003) Comparison of the effect of valsartan and lisinopril on autonomic nervous system activity in chronic heart failure. Am Heart J 146:e17

    PubMed  Google Scholar 

  42. MacFadyen R, Barr C, Struthers A (1997) Aldosterone blockade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients. Cardiovasc Res 35:30–34

    Article  CAS  PubMed  Google Scholar 

  43. Yee K, Pringle S, Allan D, Struthers A (2001) Circadian variation in the effects of aldosterone blockade on heart rate variability and QT dispersion in congestive heart failure. J Am Coll Cardiol 37:1800–1807

    Article  CAS  PubMed  Google Scholar 

  44. Korkmaz M, Muderrisoglu H, Ulucam M, Ozin B (2000) Effects of spironolactone on heart rate variability and left ventricular systolic function in severe ischemic heart failure. Am J Cardiol 86:649–653

    Article  CAS  PubMed  Google Scholar 

  45. Shehab A, Elnour A, Struthers A (2008) A randomized, controlled, double-blind, cross-over pilot study assessing the effects of spironolactone, losartan and their combination on heart rate variability and QT dispersion in patients with chronic heart failure. Cardiovasc J Afr 19:292–296

    CAS  PubMed  Google Scholar 

  46. Farquharson C, Struthers A (2002) Increasing plasma potassium with amiloride shortens the QT interval and reduces ventricular extrasystoles but does not change endothelial function or heart rate variability in chronic heart failure. Heart 88:475–480

    Article  CAS  PubMed  Google Scholar 

  47. Sal’nikov E (2009) Heart rate variability in rats with experimental chronic heart failure and long-term exposure to β-adrenoblockers. Bull Exp Biol Med 147(2):181–184

    Article  PubMed  CAS  Google Scholar 

  48. Akdeniz B, Guneri S, Savas I, Aslan O, Baris N, Badak O, Kirimli O, Goldeli O (2006) Effects of carvedilol therapy on arrhythmia markers in patients with congestive heart failure. Int Heart J 47:565–573

    Article  CAS  PubMed  Google Scholar 

  49. Hennersdorf M, Perings C, Vester E (1999) Hemodynamic effects of celiprolol in patients with ischemic and non-ischemic cardiomyopathy. Int J Cardiol 68:289–295

    Article  CAS  PubMed  Google Scholar 

  50. Copie X, Pousset F, Lechat P, Jaillon P, Guize L, Le Heuzey J (1996) Effects of beta-blockade with bisoprolol on heart rate variability in advanced heart failure: analysis of scatterplots of R-R intervals at selected heart rates. Am Heart J 132:369–375

    Article  CAS  PubMed  Google Scholar 

  51. Bullinga J, Alharethi R, Schram M, Bristow M, Gilbert E (2005) Changes in heart rate variability are correlated to hemodynamic improvement with chronic carvedilol therapy in heart failure. J Card Fail 11:693–699

    Article  CAS  PubMed  Google Scholar 

  52. Piccirillo G, Leonetti R, Celli V, Moise A, Lionetti M, Marigliano V, Cacciafesta A (2000) Effects of carvedilol on heart rate and blood pressure variability in subjects with chronic heart failure. Am J Cardiol 86:1392–1395

    Article  CAS  PubMed  Google Scholar 

  53. Goldsmith R, Bigger J, Bloomfield D, Krum H, Steinman R, Sackner-Bernstein J, Packer M (1997) Long-term carvedilol therapy increases parasympathetic nervous system activity in chronic congestive heart failure. Am J Cardiol 80:1101–1104

    Article  CAS  PubMed  Google Scholar 

  54. Aronson D, Burger A (2001) Effect of beta blockade on autonomic modulation of heart rate and neurohormonal profile in decompensated heart failure. A.N.E 6(2):98–106

    CAS  PubMed  Google Scholar 

  55. Tjeerdsma G, Szabo B, Wijk L, Brouwer J, Tio R, Crijns H, Veldhuisen D (2001) Autonomic dysfunction in patients with mild heart failure and coronary artery disease and the effects of add-on B-blockade. Eur J Heart Fail 3:33–39

    Article  CAS  PubMed  Google Scholar 

  56. Pousset F, Copie X, Lechat P, Jaillon P, Boissel J, Hetzel M, Fillette F, Remme W, Guize L, Le Heuzey J (1996) Effects of bisprolol on heart rate variability in heart failure. Am J Cardiol 77:612–617

    Article  CAS  PubMed  Google Scholar 

  57. Mortara A, La Rovere M, Pinna G, Maestri R, Capomolla S, Cobelli F (2000) Nonselective beta- adrenergic blocking agent, carvedilol, improves arterial baroreflex gain and heart rate variability in patients with stable chronic heart failure. J Am Coll Cardiol 36:1612–1618

    Article  CAS  PubMed  Google Scholar 

  58. Aquilante C, Terra S, Schofield R, Pauly D, Hatton P, Binkley P, Johnson J (2006) Sustained restoration of autonomic balance with long but not short acting metoprolol in patients with heart failure. J Card Fail 12(3):171–176

    Article  CAS  PubMed  Google Scholar 

  59. Tygesen H, Andersson B, Di Lenarda A, Rundqvist B, Sinagra G, Hjalmarson A, Waagstein F, Wennerblom B (1999) Potential risk of b-blockade withdrawal in congestive heart failure due to abrupt autonomic changes. Int J Cardiol 68:171–177

    Article  CAS  PubMed  Google Scholar 

  60. Lin J, Chan H, Du C, Lin I, Lai C, Lin K, Wu C, Tseng Y, Lien W (1999) Long-term beta-blocker therapy improves autonomic nervous regulation in advanced congestive heart failure: a longitudinal heart rate variability study. Am Heart J 137(4):658–665

    Article  CAS  PubMed  Google Scholar 

  61. Lin L, Hwang J, Lai L, Chan H, Du C, Tseng Y, Lin J (2004) Restoration of heart rate turbulence by titrated beta-blocker therapy in patients with advanced congestive heart failure: positive correlation with enhanced vagal modulation of heart rate. J Cardiovasc Electrophysiol 15:752–756

    Article  PubMed  Google Scholar 

  62. Kubo T, Parker J, Azevedo E, Atchison D, Newton G, Picton P, Floras J (2005) Vagal heart rate responses to chronic beta-blockade in human heart failure to cardiac norepinephrine spillover. Eur J Heart Fail 7:878–881

    Article  CAS  PubMed  Google Scholar 

  63. Racine N, Blanchet M, Ducharme A, Marquis J, Boucher J, Juneau M, White M (2003) Decreased heart rate recovery after exercise in patients with congestive heart failure: effect of beta blocker therapy. J Card Fail 9(4):296–302

    Article  CAS  PubMed  Google Scholar 

  64. Sanderson J, Yeung L, Chan S, Tomlinson B, Kay R, Woo K, Bernardi L (1999) Effect of b-blockade on baroreceptor and autonomic function in heart failure. Clin Sci 96:137–146

    Article  CAS  PubMed  Google Scholar 

  65. Sanderson J, Chan S, Yip G, Yeung L, Chan K, Raymond K, Woo K (1999) Beta-blockade in heart failure: a comparison of carvedilol with metoprolol. J Am Coll Cardiol 34:1522–1528

    Article  CAS  PubMed  Google Scholar 

  66. Hamaad A, Lip G, Nicholls D, MacFadyen R (2007) Comparative dose titration responses to the introduction of bisoprolol or carvedilol in stable chronic systolic heart failure. Cardiovasc Drugs Ther 21:437–444

    Article  CAS  PubMed  Google Scholar 

  67. Girgis I, Chakko S, de Marchena E, Jara C, Diaz P, Castellanos A, Myerburg R (1998) Effect of clonidine on heart rate variability in congestive heart failure. Am J Cardiol 82:335–337

    Article  CAS  PubMed  Google Scholar 

  68. You-hua Z, You-cheng S, Jun Z, Xian-qi Y (1997) Sympathetic inhibition with clonidine improves autonomic balance in congestive heart failure. Int J Cardiol 59:139–144

    Article  CAS  PubMed  Google Scholar 

  69. Cohn J, Pfeffer M, Rouleau J, Sharpe N, Swedberg K, Straub M, Wiltse C, Wright T (2003) Adverse mortality effect of central sympathetic inhibition with sustained release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail 5:659–667

    Article  CAS  PubMed  Google Scholar 

  70. Dickstein K, Manhenke C, Aarsland T, McNay J, Wiltse C, Wright T (2000) The effects of chronic, sustained-release moxonidine therapy on clinical and neurohumoral status in patients with heart failure. Int J Cardiol 75:167–176

    Article  CAS  PubMed  Google Scholar 

  71. Hauptman PJ, Kelly RA (2007) Digitalis Glycosides. In: Hosenpud JD, Greenberg BH (eds) Congestive heart failure, 3rd edn. Lippincott Williams & Wilkins, Philadelphia, pp 449–466

    Google Scholar 

  72. Krum H, Bigger J, Goldsmith R, Packer M (1995) Effect of long-term digoxin therapy on autonomic function in patients with chronic heart failure. J Am Coll Cardiol 25:289–294

    Article  CAS  PubMed  Google Scholar 

  73. Vardas P, Kanoupakis E, Kochiadakis G, Simantirakis E, Marketou M, Chlouverakis G (1998) Effects of long-term digoxin therapy on heart rate variability, baroreceptor sensitivity, and exercise capacity in patients with heart failure. Cardiovasc Drugs Ther 12:47–55

    Article  CAS  PubMed  Google Scholar 

  74. Slatton M, Irani W, Hall S, Marcoux L, Page R, Grayburn P, Eichhorn E (1997) Does digoxin provide additional hemodynamic and autonomic benefit at higher doses in patients with mild to moderate heart failure and normal sinus rhythm? J Am Coll Cardiol 29:1206–1213

    Article  CAS  PubMed  Google Scholar 

  75. Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM (2003) Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA 289:871–878

    Article  CAS  PubMed  Google Scholar 

  76. Szabo B, Van Veldhuisen D, Van Der Burgh P, Kruik J, Girbes A, Lie K (1996) Clinical and autonomic effects of ibopamine as adjunct to angiotensin-converting enzyme inhibitors in chronic heart failure. J Card Fail 2(3):185–192

    Article  CAS  PubMed  Google Scholar 

  77. Brouwer J, Van Veldhuisen D, Man in’t Veld A, Dunselman P, Boomsma F, Haaksma J, Lie K (1995) Heart rate variability in patients with mild to moderate heart failure: effects of neurohormonal modulation by digoxin and ibopamine. J Am Coll Cardiol 26:983–990

    Article  CAS  PubMed  Google Scholar 

  78. Aronson D, Burger A (2004) Effect of nesiritide (human b-type natriuretic peptide) and dobutamine on heart rate variability in decompensated heart failure. Am Heart J 148:e16

    Article  PubMed  Google Scholar 

  79. Buch A, Chowdhary S, Coote J, Townend J (2004) Effects of nitroglycerin treatment on cardiac autonomic control in heart failure. Clin Auton Res 14:9–14

    Article  PubMed  Google Scholar 

  80. Pliquett R, Cornish K, Zucker I (2003) Statin therapy restores sympathovagal balance in experimental heart failure. J Appl Physiol 95:700–704

    CAS  PubMed  Google Scholar 

  81. Gao L, Wang W, Li Y, Schultz H, Liu D, Cornish K, Zucker I (2005) Simvastatin therapy normalizes sympathetic neural control in experimental heart failure roles of angiotensin II type 1 receptors and NAD(P)H oxidase. Circulation 112:1763–1770

    Article  CAS  PubMed  Google Scholar 

  82. Katircibasi M, Canatar T, Kocum H, Erol T, Tekin G, Demircan S, Tekin A, Sezgin A, Baltali M, Muderrisoglu H (2005) Decreased heart rate recovery in patients with heart failure effect of fluvastatin therapy. Int Heart J 46:845–854

    Article  PubMed  Google Scholar 

  83. Vrtovec B, Okrajsek R, Golicnik A, Ferjan M, Starc V, Radovancevic B (2005) Atorvastatin therapy increases heart rate variability, decreases QT variability, and shortens QTc interval duration in patients with advanced chronic heart failure. J Card Fail 11(9):684–690

    Article  CAS  PubMed  Google Scholar 

  84. Hamaad A, Sosin M, Lip G, MacFadyen R (2005) Short-term adjuvant atorvastatin improves frequency domain indices of heart rate variability in stable systolic heart failure. Cardiovasc Drugs Ther 19:183–187

    Article  CAS  PubMed  Google Scholar 

  85. Gentlesk P, Wiley T, Taylor A (2005) A prospective evaluation of the effect of simvastatin on heart rate variability in non-ischemic cardiomyopathy. Am Heart J 150:478–483

    Article  CAS  PubMed  Google Scholar 

  86. Zuanetti J, Latini R, Neilson J, Schwartz P, Ewing D (1991) Heart rate variability in patients with ventricular arrhythmias: effects of antiarrhythmic drugs. J Am Coll Cardiol 17:1–604

    Article  Google Scholar 

  87. Rohde L, Polanczyk C, Moraes R, Ferlin E, Ribeiro J (1998) Effect of partial arrhythmia suppression with amiodarone on heart rate variability of patients with congestive heart failure. Am Heart J 136:31–36

    Article  CAS  PubMed  Google Scholar 

  88. Francis GS, Siegel RM, Goldsmith SR, Olivari MT, Levine TB, Cohn JN (1985) Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure: activation of the neurohumoral axis. Ann Intern Med 103:1–6

    CAS  PubMed  Google Scholar 

  89. Tomiyama H, Nakayama T, Watanabe G, Shiojima K, Sakuma Y, Yamamoto A, Imai Y, Yoshida H, Doba N (1999) Effects of short-acting and long-acting loop diuretics on heart rate variability in patients with chronic compensated congestive heart failure. Am Heart J 137:543–548

    Article  CAS  PubMed  Google Scholar 

  90. Shehab A, Butler R, MacFadyen R, Struthers A (2001) A placebo-controlled study examining the effect of allopurinol on heart rate variability and dysrhythmia counts in chronic heart failure. Br J Clin Pharmacol 51:329–334

    Article  CAS  PubMed  Google Scholar 

  91. Radaelli A, Cazzaniga M, Viola A, Balestri G, Janetti M, Signorini M, Castiglioni P, Azzellino A, Mancia G, Ferrari A (2006) Enhanced baroreceptor control of the cardiovascular system by polyunsaturated fatty acids in heart failure patients. J Am Coll Cardiol 48:1600–1606

    Article  CAS  PubMed  Google Scholar 

  92. Giannattasio C, Failla M, Stella ML et al (1995) Alterations of radial artery compliance in patients with congestive heart failure. Am J Cardiol 76:381–385

    Article  CAS  PubMed  Google Scholar 

  93. Holguin F, Tellez-Rojo M, Lazo M, Mannino D, Schwartz J, Hernandez J, Romieu I (2005) Cardiac autonomic changes associated with fish oil vs soy oil supplementation in the elderly. Chest 127:1102–1107

    Article  CAS  PubMed  Google Scholar 

  94. Mangin L, Swynghedauw B, Benis A, Thibault N, Lerebours G, Carre F (1998) Relationships between heart rate and heart rate variability: study in conscious rats. J Cardiovasc Pharmacol 32(4):601–607

    Article  CAS  PubMed  Google Scholar 

  95. Fox K, Ford I, Steg PG, Tendera M, Ferrari R (2008) Ivabradine for patients with stable coronary artery disease and left ventricular systolic dysfunction (BEAUTIFUL): a randomized, double-blind, placebo-controlled trial. Lancet 372:807–816

    Article  CAS  PubMed  Google Scholar 

  96. Swedberg K, Kamajda M, Bohm M et al (2010) Ivabradine and outcomes in chronic heart failure (SHIFT): a randomized placebo-controlled study. Lancet 376:875–885

    Article  CAS  PubMed  Google Scholar 

  97. Behling A, Moraes R, Rohde L, Ferlin E, No′brega A, Ribeiro J (2003) Cholinergic stimulation with pyridostigmine reduces ventricular arrhythmia and enhances heart rate variability in heart failure. Am Heart J 146:494–500

    Article  CAS  PubMed  Google Scholar 

  98. Serra S, Costa R, Castro R, Xavier S, Da Nobrega A (2009) Cholinergic stimulation improves autonomic and hemodynamic profile during dynamic exercise in patients with heart failure. J Card Fail 15:124–129

    Article  CAS  PubMed  Google Scholar 

  99. Hayano T, Shimizu A, Ikeda Y, Yamamoto T, Yamagata T, Ueyama T, Furutani Y, Matsuzaki M (1999) Paradoxical effects of pirenzepine on parasympathetic activity in chronic heart failure and control. Int J Cardiol 68:47–56

    Article  CAS  PubMed  Google Scholar 

  100. Venkatesh G, Fallen E, Kamath M, Connolly S, Yusuf S (1996) Double blind placebo controlled trial of transdermal scopolamine on heart rate variability in short term patients with chronic heart failure. Heart 76:137–143

    Article  CAS  PubMed  Google Scholar 

  101. Jacoby DB, Gleich GJ, Fryer AD (1993) Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor. J Clin Invest 91:1314–1318

    Article  CAS  PubMed  Google Scholar 

  102. Casadei B, Conway J, Forfar C, Sleight P (1996) Effect of low doses of scopolamine on RR interval variability, baroreflex sensitivity, and exercise performance in patients with chronic heart failure. Heart 75:274–280

    Article  CAS  PubMed  Google Scholar 

  103. La Rovere M, Mortara A, Pantaleo P, Maestri R, Cobelli F, Tavazzi L (1994) Scopolamine improves autonomic balance in advanced congestive heart failure. Circulation 90:838–843

    CAS  PubMed  Google Scholar 

  104. Okazaki Y, Zheng C, Li M, Sugimachi M (2010) Effect of the cholinesterase inhibitor donepezil on cardiac remodeling and autonomic balance in rats with heart failure. J Physiol Sci 60:67–74

    Article  CAS  PubMed  Google Scholar 

  105. Masuda Y, Kawamura A (2003) Acetylcholinesterase inhibitor (donepezil hydrochloride) reduces heart rate variability. J Cardiovasc Pharmacol 41(Suppl. 1):567–571

    Google Scholar 

  106. McLaren A, Allen J, Murray A, Ballard C, Kenny R (2003) Cardiovascular effects of donepezil in patients with dementia. Dement Geriatr Cogn Disord 15:183–188

    Article  CAS  PubMed  Google Scholar 

  107. Giubilei F, Strano S, Imbimbo P, Tisei P, Calcagnini G, Lino S, Frontoni M, Santini M, Fieschi C (1998) Cardiac autonomic dysfunction in patients with Alzheimer disease: possible pathogenetic mechanisms. Alzheimer Dis Assoc Disord 12(4):356–361

    Article  CAS  PubMed  Google Scholar 

  108. Siepmann M, Muck A, Engel S, Rupprecht R, Muck-Weymann M (2006) The influence of rivastigmine and donepezil on heart rate variability in patients with Alzheimer’s disease. German J Psych 9:133–135

    Google Scholar 

  109. Bibevski S, Dunlap M (2004) Prevention of diminished parasympathetic control of the heart in experimental heart failure. Am J Physiol Heart Circ Physiol 287:H1780–H1785

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paul J. Hauptman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Desai, M.Y., Watanabe, M.A., Laddu, A.A. et al. Pharmacologic modulation of parasympathetic activity in heart failure. Heart Fail Rev 16, 179–193 (2011). https://doi.org/10.1007/s10741-010-9195-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-010-9195-1

Keywords

Navigation