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Myocardial Innervation

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Abstract

The heart is innervated by sympathetic and parasympathetic fibers of the autonomic nervous system (ANS). The ANS plays a critical role in modifying cardiac performance to respond quickly and effectively to changing demands on cardiovascular performance. The sympathetic nervous system, which has the highest density of nerve terminals in the right and left ventricles, is predominantly stimulatory, producing positive inotropic and chronotropic effects. In contrast, the parasympathetic nervous system, which exerts primarily negative chronotropic responses, has nerve fibers predominantly in the atria [1].

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References

  1. Levy M. Sympathetic-parasympathetic interaction in the heart. In: Kulbertus HE, Franck G, editors. Neurocardiology. New York: Futura; 1988. p. 85–98.

    Google Scholar 

  2. Bristow MR, Minobe W, Rasmussen R, et al. Beta-adrenergic neuroeffector abnormalities in the failing human heart are produced by local rather than systemic mechanisms. J Clin Invest. 1992;89:803–15.

    Article  PubMed  CAS  Google Scholar 

  3. Bristow MR, Anderson FL, Port JD, et al. Differences in beta-adrenergic neuroeffector mechanisms in ischemic versus idiopathic dilated cardiomyopathy. Circulation. 1991;84:1024–39.

    Article  PubMed  CAS  Google Scholar 

  4. Somsen GA, Verberne HJ, Fleury E, Righetti A. Normal values and within-subject variability of cardiac I-123 MIBG scintigraphy in healthy individuals: implications for clinical studies. J Nucl Cardiol. 2004;11:126–33.

    Article  PubMed  Google Scholar 

  5. Momose M, Tyndale-Hines L, Bengel FM, Schwaiger M. How heterogeneous is the cardiac autonomic innervation? Basic Res Cardiol. 2001;96:539–46.

    Article  PubMed  CAS  Google Scholar 

  6. Bannister R, Mathias CJ. Introduction and classification of autonomic disorders. In: Bannister R, Mathias CJ, editors. Autonomic failure. New York: Oxford University Press; 1992. p. 1–12.

    Google Scholar 

  7. Milner P, Burnstock G. Neurotransmitters in the autonomic nervous system. In: Korczyn AD, editor. Handbook of autonomic nervous system dysfunction. New York: Marcel Dekker; 1995. p. 5–32.

    Google Scholar 

  8. Lipscombe D, Kongsamut S, Tsien RW, et al. Adrenergic inhibition of sympathetic neurotransmitter release mediated by modulation of N-type calcium-channel gating. Nature. 1989;340:639–42.

    Article  PubMed  CAS  Google Scholar 

  9. Toth PT, Bindokas VP, Bleakman D, et al. Mechanism of presynaptic inhibition by neuropeptide Y at sympathetic nerve terminals. Nature. 1993;364:635–9.

    Article  PubMed  CAS  Google Scholar 

  10. Nicholls JG, Martin AR, Wallace BG, et al. From neuron to brain: a cellular and molecular approach to the function of the nervous system. Sunderland: Sinauer; 1992.

    Google Scholar 

  11. Langer O, Halldin C. PET and SPECT tracers for mapping the cardiac nervous system. Eur J Nucl Med. 2002;29:416–34.

    Article  CAS  Google Scholar 

  12. Kline RC, Swanson DP, Wieland DM, et al. Myocardial imaging in man with I-123 meta-iodobenzylguanidine. J Nucl Med. 1981;22:129–32.

    PubMed  CAS  Google Scholar 

  13. Wieland DM, Rosenspire KC, Hutchins GD, et al. Neuronal mapping of the heart with 6-[18F]fluorometaraminol. J Med Chem. 1990;33:956–64.

    Article  PubMed  CAS  Google Scholar 

  14. Rosenspire KC, Haka MS, Van Dort ME, et al. Synthesis and preliminary evaluation of carbon-11-meta-hydroxyephedrine: a false transmitter agent for heart neuronal imaging. J Nucl Med. 1990;31:1328–34.

    PubMed  CAS  Google Scholar 

  15. Raffel DM, Corbett JR, del Rosario RB, et al. Clinical evaluation of carbon-11-phenylephrine: MAO-sensitive marker of cardiac sympathetic neurons. J Nucl Med. 1996;37:1923–31.

    PubMed  CAS  Google Scholar 

  16. Degrado TR, Zalutsky MR, Vaidyanathan G. Uptake mechanisms of meta-[123I]iodobenzylguanidine in isolated rat heart. Nucl Med Biol. 1995;22:1–12.

    Article  PubMed  CAS  Google Scholar 

  17. Nakajima K, Taki J, Tonami N, Hisada K. Decreased 123I-MIBG uptake and increased clearance in various cardiac diseases. Nucl Med Commun. 1994;15:317–23.

    Article  PubMed  CAS  Google Scholar 

  18. Bengel FM, Barthel P, Matsunari I, et al. Kinetics of 123I-MIBG after acute myocardial infarction and reperfusion therapy. J Nucl Med. 1999;40:904–10.

    PubMed  CAS  Google Scholar 

  19. Yamada T, Shimonagata T, Fukunami M, et al. Comparison of the prognostic value of cardiac iodine-123 metaiodobenzylguanidine imaging and heart rate variability in patients with chronic heart failure: a prospective study. J Am Coll Cardiol. 2003;41:231–8.

    Article  PubMed  Google Scholar 

  20. Patel A, Iskandrian A. MIBG imaging. J Nucl Cardiol. 2002;9:75–94.

    Article  PubMed  Google Scholar 

  21. Farahati J, Bier D, Scheubeck M, et al. Effect of specific activity on cardiac uptake of iodine-123-MIBG. J Nucl Med. 1997;38:447–51.

    PubMed  CAS  Google Scholar 

  22. DeGrado TR, Zalutsky MR, Coleman RE, Vaidyanathan G. Effects of specific activity on meta-[(131)I]iodobenzylguanidine kinetics in isolated rat heart. Nucl Med Biol. 1998;25:59–64.

    Article  PubMed  CAS  Google Scholar 

  23. Verberne HJ, Brewster LM, Somsen GA, van Eck-Smit BL. Prognostic value of myocardial 123I-metaiodobenzylguanidine (MIBG) parameters in patients with heart failure: a systematic review. Eur Heart J. 2008;29:1147–59.

    Article  PubMed  Google Scholar 

  24. Schwaiger M, Kalff V, Rosenspire K, et al. Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography. Circulation. 1990;82:457–64.

    Article  PubMed  CAS  Google Scholar 

  25. Schwaiger M, Hutchins GD, Kalff V, et al. Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomography. J Clin Invest. 1991;87:1681–90.

    Article  PubMed  CAS  Google Scholar 

  26. Munch G, Nguyen N, Nekolla S, et al. Evaluation of sympathetic nerve terminals with [(11)C] epinephrine and [(11)D]hydroxyephedrine and positron emission tomography. Circulation. 2000;101:516–23.

    Article  PubMed  CAS  Google Scholar 

  27. Delforge J, Syrota A, Lancon JP, et al. Cardiac beta-adrenergic receptor density measured in vivo using PET, CGP 12177, and a new graphical method. J Nucl Med. 1991;32:739–48. [published erratum appears in J Nucl Med. 1994;35(5):921].

    PubMed  CAS  Google Scholar 

  28. Hartmann F, Ziegler S, Nekolla S, et al. Regional patterns of myocardial sympathetic denervation in dilated cardiomyopathy: an analysis using carbon-11 hydroxyephedrine and positron emission tomography. Heart. 1999;81:262–70.

    PubMed  CAS  Google Scholar 

  29. Caldwell JH, Link JM, Levy WC, et al. Evidence for pre- to postsynaptic mismatch of the cardiac sympathetic nervous system in ischemic congestive heart failure. J Nucl Med. 2008;49:234–41.

    Article  PubMed  Google Scholar 

  30. Wakabayashi T, Nakata T, Hashimoto A, Yuda S, Tsuchihashi K, Travin MI, et al. Assessment of underlying etiology and cardiac sympathetic innervation to identify patients at high risk of cardiac death. J Nucl Med. 2001;42:1757–67.

    PubMed  CAS  Google Scholar 

  31. Momose M, Kobayashi H, Iguchi N, Matsuda N, Sakomura Y, Kasanuki H, et al. Comparison of parameters of 123I-mIBG scintigraphy for predicting prognosis in patients with dilated cardiomyopathy. Nucl Med Commun. 1999;20:529–35.

    Article  PubMed  CAS  Google Scholar 

  32. Merlet P, Benvenuti C, Moyse D, Pouillart F, Dubois-Rande JL, Duval AM, et al. Prognostic value of MIBG imaging in idiopathic dilated cardiomyopathy. J Nucl Med. 1999;40:917–23.

    PubMed  CAS  Google Scholar 

  33. Nakata T, Wakabayashi T, Kyuma M, Takahashi T, Tsuchihashi K, Shimamoto K. Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure. Eur J Nucl Med Mol Imaging. 2005;32:186–94.

    Article  PubMed  CAS  Google Scholar 

  34. Kuwabara Y, Tamaki N, Nakata T, Yamashina S, Yamazaki J. Determination of the survival rate in patients with congestive heart failure stratified by 123I-MIBG imaging: a meta-analysis from the studies performed in Japan. Ann Nucl Med. 2011;25:101–7.

    Article  PubMed  Google Scholar 

  35. Somsen GA, van Vlies B, de Milliano PA, et al. Increased myocardial [123I]-metaiodobenzylguanidine uptake after enalapril treatment in patients with chronic heart failure. Heart. 1996;76:218–22.

    Article  PubMed  CAS  Google Scholar 

  36. Kasama S, Toyama T, Kumakura H, et al. Effects of candesartan on cardiac sympathetic nerve activity in patients with congestive heart failure and preserved left ventricular ejection fraction. J Am Coll Cardiol. 2005;45:661–7.

    Article  PubMed  CAS  Google Scholar 

  37. Suwa M, Otake Y, Moriguchi A, et al. Iodine-123 metaiodobenzylguanidine myocardial scintigraphy for prediction of response to beta-blocker therapy in patients with dilated cardiomyopathy. Am Heart J. 1997;133:353–8.

    Article  PubMed  CAS  Google Scholar 

  38. Kasama S, Toyama T, Hatori T, et al. Evaluation of cardiac sympathetic nerve activity and left ventricular remodelling in patients with dilated cardiomyopathy on the treatment containing carvedilol. Eur Heart J. 2007;28:989–95.

    Article  PubMed  CAS  Google Scholar 

  39. Cohen-Solal A, Rouzet F, Berdeaux A, et al. Effects of carvedilol on myocardial sympathetic innervation in patients with chronic heart failure. J Nucl Med. 2005;46:1796–803.

    PubMed  CAS  Google Scholar 

  40. Kasama S, Toyama T, Kumakura H, et al. Effect of spironolactone on cardiac sympathetic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy. J Am Coll Cardiol. 2003;41:574–81.

    Article  PubMed  CAS  Google Scholar 

  41. Erol-Yilmaz A, Verberne HJ, Schrama TA, et al. Cardiac resynchronization induces favorable neurohumoral changes. Pacing Clin Electrophysiol. 2005;28:304–10.

    Article  PubMed  Google Scholar 

  42. Nishioka SA, Martinelli Filho M, Brandão SC, et al. Cardiac sympathetic activity pre and post resynchronization therapy evaluated by 123I-MIBG myocardial scintigraphy. J Nucl Cardiol. 2007;14:852–9.

    Article  PubMed  Google Scholar 

  43. Gould PA, Kong G, Kalff V, et al. Improvement in cardiac adrenergic function post biventricular pacing for heart failure. Europace. 2007;9:751–6.

    Article  PubMed  Google Scholar 

  44. Agostini D, Verberne HJ, Burchert W, et al. I-123-mIBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients: insights from a retrospective European multicenter study. Eur J Nucl Med Mol Imaging. 2008;35:535–46.

    Article  PubMed  Google Scholar 

  45. Jacobson AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, et al. Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol. 2010;55:2212–21.

    Article  PubMed  Google Scholar 

  46. Narula J, Cerqueira MD, Senior R, Travin M, Thomas GS, Clements IP, Jacobson AF. 123I-mIBG myocardial scintigraphy and left ventricular ejection fraction for defining risk for ventricular arrhythmic events and death in heart failure patients: results from the ADMIRE-HF Extension (X) Trial. Presented at the American Heart Association 2010 annual meeting, Chicago, 2010.

    Google Scholar 

  47. Allman KC, Wieland DM, Muzik O, et al. Carbon-11 hydroxyephedrine with positron emission tomography for serial assessment of cardiac adrenergic neuronal function after acute myocardial infarction in humans. J Am Coll Cardiol. 1993;22:368–75.

    Article  PubMed  CAS  Google Scholar 

  48. Matsunari I, Schricke U, Bengel FM, et al. Extent of cardiac sympathetic neuronal damage is determined by the area of ischemia in patients with acute coronary syndromes. Circulation. 2000;101:2579–85.

    Article  PubMed  CAS  Google Scholar 

  49. Frickel E, Frickel H, Eckert S, et al. Myocardial sympathetic innervation in patients with chronic coronary artery disease: is reduction in coronary flow reserve correlated with sympathetic denervation? Eur J Nucl Med Mol Imaging. 2007;34:206–11.

    Article  Google Scholar 

  50. Yukinaka M, Nomura M, Ito S, Nakaya Y. Mismatch between myocardial accumulation of 123I-MIBG and 99mTc-MIBI and late ventricular potentials in patients after myocardial infarction: association with the development of ventricular arrhythmias. Am Heart J. 1998;136:859–67.

    Article  PubMed  CAS  Google Scholar 

  51. Simões MV, Barthel P, Matsunari I, et al. Presence of sympathetically denervated but viable myocardium and its electrophysiologic correlates after early revascularised, acute myocardial infarction. Eur Heart J. 2004;25:551–7.

    Article  PubMed  Google Scholar 

  52. Calkins H, Allman K, Bolling S, et al. Correlation between scintigraphic evidence of regional sympathetic neuronal ­dysfunction and ventricular refractoriness in the human heart. Circulation. 1993;88:172–9.

    Article  PubMed  CAS  Google Scholar 

  53. Sasano T, Abraham MR, Chang KC, et al. Abnormal sympathetic innervation of viable myocardium and the substrate of ventricular tachycardia after myocardial infarction. J Am Coll Cardiol. 2008;51:2266–75.

    Article  PubMed  Google Scholar 

  54. Akutsu Y, Kaneko K, Kodama Y, et al. Iodine-123 Imaging for predicting the development of atrial fibrillation. JACC Cardiovasc Imaging. 2011;4:78–86.

    Article  PubMed  Google Scholar 

  55. Schwartz PJ. The autonomic nervous system and sudden death. Eur Heart J. 1998;19:F72–80.

    Article  PubMed  Google Scholar 

  56. Meredith IT, Broughton A, Jennings GL, Esler MD. Evidence of a selective increase in cardiac sympathetic activity in patients with sustained ventricular arrhythmias. N Engl J Med. 1991;325:618–24.

    Article  PubMed  CAS  Google Scholar 

  57. Rubart M, Zipes DP. Mechanisms of sudden cardiac death. J Clin Invest. 2005;115:2305–15.

    Article  PubMed  CAS  Google Scholar 

  58. Wichter T, Schafers M, Rhodes CG, et al. Abnormalities of cardiac sympathetic innervation in arrhythmogenic right ventricular cardiomyopathy: quantitative assessment of presynaptic norepinephrine reuptake and postsynaptic beta-adrenergic receptor density with positron emission tomography. Circulation. 2000;101:1552–8.

    Article  PubMed  CAS  Google Scholar 

  59. Schafers M, Lerch H, Wichter T, et al. Cardiac sympathetic innervation in patients with idiopathic right ventricular outflow tract tachycardia. J Am Coll Cardiol. 1998;32:181–6.

    Article  PubMed  CAS  Google Scholar 

  60. Kies P, Wichte T, Schafers M, et al. Abnormal myocardial presynaptic norepinephrine recycling in patients with Brugada syndrome. Circulation. 2004;110:3017–22.

    Article  PubMed  CAS  Google Scholar 

  61. Paul M, Schäfers M, Kies P, et al. Impact of sympathetic innervation on recurrent life-threatening arrhythmias in the follow-up of patients with idiopathic ventricular fibrillation. Eur J Nucl Med Mol Imaging. 2006;33:866–70.

    Article  PubMed  Google Scholar 

  62. Arora R, Ferick K, Nakata T, et al. I-123 MIBG imaging and heart rate variability analysis to predict the need for an implantable cardioverter defibrillator. J Nucl Cardiol. 2003;10:121–31.

    Article  PubMed  Google Scholar 

  63. Nagahara D, Nakata T, Hashimoto A, et al. Predicting the need for an implantable cardioverter defibrillator using cardiac metaiodobenzylguanidine activity together with plasma natriuretic peptide concentration or left ventricular function. J Nucl Med. 2008;49:225–33.

    Article  PubMed  Google Scholar 

  64. Langen KJ, Ziegler D, Weise F, et al. Evaluation of QT interval length, QT dispersion and myocardial m-iodobenzylguanidine uptake in insulin-dependent diabetic patients with and without autonomic neuropathy. Clin Sci. 1997;93:325–33.

    PubMed  CAS  Google Scholar 

  65. Stevens MJ, Raffel DM, Allman KC, et al. Cardiac sympathetic dysinnervation in diabetes: implications for enhanced cardiovascular risk. Circulation. 1998;98:961–8.

    Article  PubMed  CAS  Google Scholar 

  66. Pop-Busui R, Kirkwood I, Schmid H, et al. Sympathetic dysfunction in type 1 diabetes: association with impaired myocardial blood flow reserve and diastolic dysfunction. J Am Coll Cardiol. 2004;44:2368–74.

    Article  PubMed  CAS  Google Scholar 

  67. Allman KC, Stevens MJ, Wieland DM, et al. Noninvasive assessment of cardiac diabetic neuropathy by carbon-11 hydroxyephedrine and positron emission tomography. J Am Coll Cardiol. 1993;22:1425–32.

    Article  PubMed  CAS  Google Scholar 

  68. Ziegler D, Weise F, Langen KJ, et al. Effect of glycaemic control on myocardial sympathetic innervation assessed by [123I]metaiodobenzylguanidine scintigraphy: a 4-year prospective study in IDDM patients. Diabetologia. 1998;41:443–51.

    Article  PubMed  CAS  Google Scholar 

  69. Wei K, Dorian P, Newman D, Langer A. Association between QT dispersion and autonomic dysfunction in patients with diabetes mellitus. J Am Coll Cardiol. 1995;26:859–63.

    Article  PubMed  CAS  Google Scholar 

  70. Odaka K, von Scheidt W, Ziegler SI, et al. Reappearance of cardiac presynaptic sympathetic nerve terminals in the transplanted heart: correlation between PET using (11)C-hydroxyephedrine and invasively measured norepinephrine release. J Nucl Med. 2001;42:1011–6.

    PubMed  CAS  Google Scholar 

  71. Bengel FM, Ueberfuhr P, Schiepel N, et al. Effect of sympathetic reinnervation on cardiac performance after heart transplantation. N Engl J Med. 2001;345:731–8.

    Article  PubMed  CAS  Google Scholar 

  72. De Marco T, Dae M, Yuen-Green MS, et al. Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: evidence for late reinnervation. J Am Coll Cardiol. 1995;25:927–31.

    Article  PubMed  Google Scholar 

  73. Estorch M, Camprecios M, Flotats A, et al. Sympathetic reinnervation of cardiac allografts evaluated by 123I-MIBG imaging. J Nucl Med. 1999;40:911–6.

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Technical University of Munich, Munich, Germany

    Markus Schwaiger M.D.

  2. Turku PET Centre, Turku University Hospital, Turku, Finland

    Antti Saraste M.D., Ph.D.

  3. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany

    Frank M. Bengel M.D.

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  1. Markus Schwaiger M.D.
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  2. Antti Saraste M.D., Ph.D.
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  3. Frank M. Bengel M.D.
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Editors and Affiliations

  1. School of Medicine, Dept. Diagnostic Radiology, University Maryland, S. Greene Street 22, Baltimore, 21201, Maryland, USA

    Vasken Dilsizian

  2. , Department of Cardiology, Mount Sinai School of Medicine and Medic, Gustave L. Levy Place 1, New York, 10029, New York, USA

    Jagat Narula

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Schwaiger, M., Saraste, A., Bengel, F.M. (2013). Myocardial Innervation. In: Dilsizian, V., Narula, J. (eds) Atlas of Nuclear Cardiology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5551-6_11

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