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Evidence for impaired vagus nerve activity in heart failure

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Abstract

Parasympathetic control of the heart via the vagus nerve is the primary mechanism that regulates beat-to-beat control of heart rate. Additionally, the vagus nerve exerts significant effects at the AV node, as well as effects on both atrial and ventricular myocardium. Vagal control is abnormal in heart failure, occurring at early stages of left ventricular dysfunction, and this reduced vagal function is associated with worse outcomes in patients following myocardial infarction and with heart failure. While central control mechanisms are abnormal, one of the primary sites of attenuated vagal control is at the level of the parasympathetic ganglion. It remains to be seen whether or not preventing or treating abnormal vagal control of the heart improves prognosis.

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References

  1. Domanski MJ, Krause-Steinrauf H, Massie BM, Deedwania P, Follmann D, Kovar D, Murray D, Oren R, Rosenberg Y, Young J, Zile M, Eichhorn E (2003) A comparative analysis of the results from 4 trials of beta-blocker therapy for heart failure: BEST, CIBIS-II, MERIT-HF, and COPERNICUS. J Card Fail 9:354–363

    Article  CAS  PubMed  Google Scholar 

  2. Javed U (2009) Deedwania PC: Beta-adrenergic blockers for chronic heart failure. Cardiol Rev 17:287–292

    Article  PubMed  Google Scholar 

  3. Esler M, Kaye D, Lambert G, Esler D, Jennings G (1997) Adrenergic nervous system in heart failure. Am J Cardiol 80:7L–14L

    Article  CAS  PubMed  Google Scholar 

  4. Olshansky B, Sabbah HN, Hauptman PJ, Colucci WS (2008) Parasympathetic nervous system and heart failure: pathophysiology and potential implications for therapy. Circulation 118:863–871

    Article  PubMed  Google Scholar 

  5. Bibevski S, Dunlap ME (1999) Ganglionic mechanisms contribute to diminished vagal control in heart failure. Circulation 99:2958–2963

    CAS  PubMed  Google Scholar 

  6. Binkley PF, Nunziata E, Haas GJ, Nelson SD, Cody RJ (1991) Parasympathetic withdrawal is an integral component of autonomic imbalance in congestive heart failure: demonstration in human subjects and verification in a paced canine model of ventricular failure. J Am Coll Cardiol 18:464–472

    Article  CAS  PubMed  Google Scholar 

  7. Kinugawa T, Dibner-Dunlap ME (1995) Altered vagal and sympathetic control of heart rate in left ventricular dysfunction and heart failure. Am J Physiol 268:R317–R323

    CAS  PubMed  Google Scholar 

  8. Bibevski S, Dunlap ME (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 

  9. Plecha DM, Randall WC, Geis GS, Wurster RD (1988) Localization of vagal preganglionic somata controlling sinoatrial and atrioventricular nodes. Am J Physiol 255:R703–R708

    CAS  PubMed  Google Scholar 

  10. Bluemel KM, Wurster RD, Randall WC, Duff MJ, O’Toole MF (1990) Parasympathetic postganglionic pathways to the sinoatrial node. Am J Physiol 259:H1504–H1510

    CAS  PubMed  Google Scholar 

  11. Geis WP, Kaye MP, Randall WC (1973) Major autonomic pathways to the atria and S-A and A-V nodes of the canine heart. Am J Physiol 224:202–208

    CAS  PubMed  Google Scholar 

  12. Billman GE, Hoskins RS, Randall DC, Randall WC, Hamlin RL, Lin YC (1989) Selective vagal postganglionic innervation of the sinoatrial and atrioventricular nodes in the non-human primate. J Auton Nerv Syst 26:27–36

    Article  CAS  PubMed  Google Scholar 

  13. Randall WC, Ardell JL, Wurster RD, Milosavljevic M (1987) Vagal postganglionic innervation of the canine sinoatrial node. J Auton Nerv Syst 20:13–23

    Article  CAS  PubMed  Google Scholar 

  14. Carlson MD, Geha AS, Hsu J, Martin PJ, Levy MN, Jacobs G, Waldo AL (1992) Selective stimulation of parasympathetic nerve fibers to the human sinoatrial node. Circulation 85:1311–1317

    CAS  PubMed  Google Scholar 

  15. Gatti PJ, Johnson TA, Massari VJ (1996) Can neurons in the nucleus ambiguus selectively regulate cardiac rate and atrio-ventricular conduction? J Auton Nerv Syst 57:123–127

    Article  CAS  PubMed  Google Scholar 

  16. Ardell JL, Randall WC (1986) Selective vagal innervation of sinoatrial and atrioventricular nodes in canine heart. Am J Physiol 251:H764–H773

    CAS  PubMed  Google Scholar 

  17. Armour JA, Linderoth B, Arora RC, DeJongste MJ, Ardell JL, Kingma JG Jr, Hill M, Foreman RD (2002) Long-term modulation of the intrinsic cardiac nervous system by spinal cord neurons in normal and ischaemic hearts. Auton Neurosci 95:71–79

    Article  CAS  PubMed  Google Scholar 

  18. Thompson GW, Collier K, Ardell JL, Kember G, Armour JA (2000) Functional interdependence of neurons in a single canine intrinsic cardiac ganglionated plexus. J Physiol 528:561–571

    Article  CAS  PubMed  Google Scholar 

  19. DiFrancesco D (2005) Cardiac pacemaker I(f) current and its inhibition by heart rate-reducing agents. Curr Med Res Opin 21:1115–1122

    Article  CAS  PubMed  Google Scholar 

  20. Gorfe AA, Chang CE, Ivanov I, McCammon JA (2008) Dynamics of the acetylcholinesterase tetramer. Biophys J 94:1144–1154

    Article  CAS  PubMed  Google Scholar 

  21. Henning RJ, Khalil IR, Levy MN (1990) Vagal stimulation attenuates sympathetic enhancement of left ventricular function. Am J Physiol 258:H1470–H1475

    CAS  PubMed  Google Scholar 

  22. Randall DC, Brown DR, McGuirt AS, Thompson GW, Armour JA, Ardell JL (2003) Interactions within the intrinsic cardiac nervous system contribute to chronotropic regulation. Am J Physiol Regul Integr Comp Physiol 285:R1066–R1075

    CAS  PubMed  Google Scholar 

  23. Dickerson LW, Rodak DJ, Fleming TJ, Gatti PJ, Massari VJ, McKenzie JC, Gillis RA (1998) Parasympathetic neurons in the cranial medial ventricular fat pad on the dog heart selectively decrease ventricular contractility. J Auton Nerv Syst 70:129–141

    Article  CAS  PubMed  Google Scholar 

  24. Mick JD, Wurster RD, Duff M, Weber M, Randall WC, Randall DC (1992) Epicardial sites for vagal mediation of sinoatrial function. Am J Physiol 262:H1401–H1406

    CAS  PubMed  Google Scholar 

  25. Furukawa Y, Wallick DW, Carlson MD, Martin PJ (1990) Cardiac electrical responses to vagal stimulation of fibers to discrete cardiac regions. Am J Physiol 258:H1112–H1118

    CAS  PubMed  Google Scholar 

  26. Arora RC, Cardinal R, Smith FM, Ardell JL, Dell’Italia LJ, Armour JA (2003) Intrinsic cardiac nervous system in tachycardia induced heart failure. Am J Physiol Regul Integr Comp Physiol 285:R1212–R1223

    CAS  PubMed  Google Scholar 

  27. Eckberg DL, Drabinsky M, Braunwald E (1971) Defective cardiac parasympathetic control in patients with heart disease. N Engl J Med 285:877–883

    Article  CAS  PubMed  Google Scholar 

  28. Bauer A, Malik M, Schmidt G, Barthel P, Bonnemeier H, Cygankiewicz I, Guzik P, Lombardi F, Muller A, Oto A, Schneider R, Watanabe M, Wichterle D, Zareba W (2008) Heart rate turbulence: standards of measurement, physiological interpretation, and clinical use: International Society for Holter and Noninvasive Electrophysiology Consensus. J Am Coll Cardiol 52:1353–1365

    Article  PubMed  Google Scholar 

  29. Motte S, Mathieu M, Brimioulle S, Pensis A, Ray L, Ketelslegers JM, Montano N, Naeije R, van de BP, Entee KM (2005) Respiratory-related heart rate variability in progressive experimental heart failure. Am J Physiol Heart Circ Physiol 289:H1729–H1735

    Article  CAS  PubMed  Google Scholar 

  30. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ (1987) Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59:256–262

    Article  CAS  PubMed  Google Scholar 

  31. La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet 351:478–484

    Google Scholar 

  32. Schwartz PJ, La Rovere MT, Vanoli E (1992) Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. Circulation 85:I77–I91

    CAS  Google Scholar 

  33. Herring N, Paterson DJ (2009) Neuromodulators of peripheral cardiac sympatho-vagal balance. Exp Physiol 94:46–53

    Article  CAS  PubMed  Google Scholar 

  34. Nihei M, Lee JK, Honjo H, Yasui K, Uzzaman M, Kamiya K, Opthof T, Kodama I (2005) Decreased vagal control over heart rate in rats with right-sided congestive heart failure: downregulation of neuronal nitric oxide synthase. Circ J 69:493–499

    Article  CAS  PubMed  Google Scholar 

  35. Dunlap ME, Bibevski S, Rosenberry TL, Ernsberger P (2003) Mechanisms of altered vagal control in heart failure: influence of muscarinic receptors and acetylcholinesterase activity. Am J Physiol Heart Circ Physiol 285:H1632–H1640

    CAS  PubMed  Google Scholar 

  36. Vatner DE, Sato N, Galper JB, Vatner SF (1996) Physiological and biochemical evidence for coordinate increases in muscarinic receptors and Gi during pacing-induced heart failure. Circulation 94:102–107

    CAS  PubMed  Google Scholar 

  37. McGehee DS, Role LW (1995) Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. Annu Rev Physiol 57:521–546

    Article  CAS  PubMed  Google Scholar 

  38. Bibevski S, Zhou Y, McIntosh JM, Zigmond RE, Dunlap ME (2000) Functional nicotinic acetylcholine receptors that mediate ganglionic transmission in cardiac parasympathetic neurons. J Neurosci 20:5076–5082

    CAS  PubMed  Google Scholar 

  39. Xu W, Orr-Urtreger A, Nigro F, Gelber S, Sutcliffe CB, Armstrong D, Patrick JW, Role LW, Beaudet AL, De BM (1999) Multiorgan autonomic dysfunction in mice lacking the beta2 and the beta4 subunits of neuronal nicotinic acetylcholine receptors. J Neurosci 19:9298–9305

    CAS  PubMed  Google Scholar 

  40. Xu W, Gelber S, Orr-Urtreger A, Armstrong D, Lewis RA, Ou CN, Patrick J, Role L, De BM, Beaudet AL (1999) Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor. Proc Natl Acad Sci USA 96:5746–5751

    Article  CAS  PubMed  Google Scholar 

  41. Du XJ, Cox HS, Dart AM, Esler MD (1998) Depression of efferent parasympathetic control of heart rate in rats with myocardial infarction: effect of losartan. J Cardiovasc Pharmacol 31:937–944

    Article  CAS  PubMed  Google Scholar 

  42. Binkley PF, Haas GJ, Starling RC, Nunziata E, Hatton PA, Leier CV, Cody RJ (1993) Sustained augmentation of parasympathetic tone with angiotensin-converting enzyme inhibition in patients with congestive heart failure. J Am Coll Cardiol 21:655–661

    Article  CAS  PubMed  Google Scholar 

  43. Malfatto G, Facchini M, Branzi G, Riva B, Sala L, Perego GB (2003) Long-term treatment with the beta-blocker carvedilol restores autonomic tone and responsiveness in patients with moderate heart failure. J Cardiovasc Pharmacol 42:125–131

    Article  CAS  PubMed  Google Scholar 

  44. Sanderson EM, Drasdo AL, McCrea K, Wonnacott S (1993) Upregulation of nicotinic receptors following continuous infusion of nicotine is brain-region-specific. Brain Res 617:349–352

    Article  CAS  PubMed  Google Scholar 

  45. Wonnacott S (1990) The paradox of nicotinic acetylcholine receptor upregulation by nicotine. Trends Pharmacol Sci 11:216–219

    Article  CAS  PubMed  Google Scholar 

  46. Zhang Y, Popovic ZB, Bibevski S, Fakhry I, Sica DA, Van Wagoner DR, Mazgalev TN (2009) 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 2:692–699

    Article  CAS  PubMed  Google Scholar 

  47. Qin F, Vulapalli RS, Stevens SY, Liang CS (2002) Loss of cardiac sympathetic neurotransmitters in heart failure and NE infusion is associated with reduced NGF. Am J Physiol Heart Circ Physiol 282:H363–H371

    CAS  PubMed  Google Scholar 

  48. Okoshi K, Nakayama M, Yan X, Okoshi MP, Schuldt AJ, Marchionni MA, Lorell BH (2004) Neuregulins regulate cardiac parasympathetic activity: muscarinic modulation of beta-adrenergic activity in myocytes from mice with neuregulin-1 gene deletion. Circulation 110:713–717

    Article  CAS  PubMed  Google Scholar 

  49. Lemmens K, Doggen K, De Keulenaer GW (2007) Role of neuregulin-1/ErbB signaling in cardiovascular physiology and disease: implications for therapy of heart failure. Circulation 116:954–960

    Article  CAS  PubMed  Google Scholar 

  50. Herring N, Danson EJ, Paterson DJ (2002) Cholinergic control of heart rate by nitric oxide is site specific. News Physiol Sci 17:202–206

    CAS  PubMed  Google Scholar 

  51. Hare JM, Colucci WS (1995) Role of nitric oxide in the regulation of myocardial function. Prog Cardiovasc Dis 38:155–166

    Article  CAS  PubMed  Google Scholar 

  52. Schultz HD (2009) Nitric oxide regulation of autonomic function in heart failure. Curr Heart Fail Rep 6:71–80

    Article  CAS  PubMed  Google Scholar 

  53. Champion HC, Skaf MW, Hare JM (2003) Role of nitric oxide in the pathophysiology of heart failure. Heart Fail Rev 8:35–46

    Article  CAS  PubMed  Google Scholar 

  54. Potter EK (1982) Peripheral inhibition of the parasympathetic nervous system by angiotensin. Clin Exp Pharmacol Physiol Suppl 7:51–55

    CAS  PubMed  Google Scholar 

  55. Potter EK (1982) Angiotensin inhibits action of vagus nerve at the heart. Br J Pharmacol 75:9–11

    CAS  PubMed  Google Scholar 

  56. Kawada T, Yamazaki T, Akiyama T, Li M, Zheng C, Shishido T, Mori H, Sugimachi M (2007) Angiotensin II attenuates myocardial interstitial acetylcholine release in response to vagal stimulation. Am J Physiol Heart Circ Physiol 293:H2516–H2522

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, University of Michigan Cardiovascular Center, 5144 Cardiovascular Center, 1500 E. Medical Center Drive SPC 5864, Ann Arbor, MI, 48109, USA

    Steve Bibevski

  2. Heart Failure Section, Heart and Vascular Center, Metrohealth Medical Center, 2500 MetroHealth Dr., Cleveland, OH, 44109, USA

    Mark E. Dunlap

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  1. Steve Bibevski
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Correspondence to Mark E. Dunlap.

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Bibevski, S., Dunlap, M.E. Evidence for impaired vagus nerve activity in heart failure. Heart Fail Rev 16, 129–135 (2011). https://doi.org/10.1007/s10741-010-9190-6

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