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Front Physiol. 2020 Dec 22;11:617459. doi: 10.3389/fphys.2020.617459. eCollection 2020.

Autonomic Modulation for Cardiovascular Disease.

Frontiers in physiology

Joseph Hadaya, Jeffrey L Ardell

Affiliations

  1. University of California, Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, Los Angeles, CA, United States.
  2. UCLA Neurocardiology Research Program of Excellence, UCLA, Los Angeles, CA, United States.
  3. Molecular, Cellular, and Integrative Physiology Program, UCLA, Los Angeles, CA, United States.

PMID: 33414727 PMCID: PMC7783451 DOI: 10.3389/fphys.2020.617459

Abstract

Dysfunction of the autonomic nervous system has been implicated in the pathogenesis of cardiovascular disease, including congestive heart failure and cardiac arrhythmias. Despite advances in the medical and surgical management of these entities, progression of disease persists as does the risk for sudden cardiac death. With improved knowledge of the dynamic relationships between the nervous system and heart, neuromodulatory techniques such as cardiac sympathetic denervation and vagal nerve stimulation (VNS) have emerged as possible therapeutic approaches for the management of these disorders. In this review, we present the structure and function of the cardiac nervous system and the remodeling that occurs in disease states, emphasizing the concept of increased sympathoexcitation and reduced parasympathetic tone. We review preclinical evidence for vagal nerve stimulation, and early results of clinical trials in the setting of congestive heart failure. Vagal nerve stimulation, and other neuromodulatory techniques, may improve the management of cardiovascular disorders, and warrant further study.

Copyright © 2020 Hadaya and Ardell.

Keywords: arrhythmia; autonomic nervous system; heart failure; myocardial infaraction; neurocardiology; neuromodulation; sympathectomy; vagus nerve

Conflict of interest statement

University of California, Los Angeles has patents developed by JLA relating to cardiac neural diagnostics and therapeutics. JLA is a co-founder of NeuCures, Inc. The remaining author declares that the

References

  1. J Card Fail. 2014 Nov;20(11):808-16 - PubMed
  2. Cardiovasc Res. 2017 Sep 1;113(11):1318-1328 - PubMed
  3. Science. 1994 Jan 14;263(5144):232-4 - PubMed
  4. J Physiol. 2016 Jul 15;594(14):3877-909 - PubMed
  5. J Am Coll Cardiol. 2012 Mar 6;59(10):954-61 - PubMed
  6. Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H311-7 - PubMed
  7. Am J Physiol Heart Circ Physiol. 2020 Mar 1;318(3):H558-H565 - PubMed
  8. Circulation. 2010 Jun 1;121(21):2255-62 - PubMed
  9. Circ Res. 1973 Feb;32(2):215-20 - PubMed
  10. Handb Exp Pharmacol. 2009;(194):185-225 - PubMed
  11. Annu Rev Neurosci. 2014;37:387-407 - PubMed
  12. Clin Exp Pharmacol Physiol. 1996 Aug;23(8):700-8 - PubMed
  13. Heart Vessels. 2003 Mar;18(1):32-9 - PubMed
  14. Compr Physiol. 2016 Sep 15;6(4):1635-1653 - PubMed
  15. Heart Rhythm. 2012 Aug;9(8):1303-9 - PubMed
  16. Am J Physiol Heart Circ Physiol. 2013 Oct 1;305(7):H1020-30 - PubMed
  17. J Comp Neurol. 1984 Oct 20;229(2):186-98 - PubMed
  18. Prog Brain Res. 1996;107:79-96 - PubMed
  19. Circulation. 1991 Jul;84(1):357-67 - PubMed
  20. Eur Heart J. 2011 Apr;32(7):847-55 - PubMed
  21. Anat Embryol (Berl). 2005 Jul;209(6):425-38 - PubMed
  22. Am J Physiol. 1993 Jan;264(1 Pt 2):R1-7 - PubMed
  23. Am J Physiol. 1997 Jun;272(6 Pt 2):H2525-33 - PubMed
  24. Can J Physiol Pharmacol. 1988 Feb;66(2):119-27 - PubMed
  25. Physiol Rev. 1983 Jan;63(1):1-205 - PubMed
  26. N Engl J Med. 1992 Sep 3;327(10):669-77 - PubMed
  27. J Physiol. 1973 Mar;229(2):457-69 - PubMed
  28. Heart Rhythm. 2017 Nov;14(11):1665-1672 - PubMed
  29. Circ Heart Fail. 2015 May;8(3):619-28 - PubMed
  30. Exp Physiol. 2008 Feb;93(2):165-76 - PubMed
  31. J Physiol. 2016 Jul 15;594(14):3851-2 - PubMed
  32. Heart Rhythm. 2017 Jul;14(7):1063-1070 - PubMed
  33. Cardiovasc Res. 2004 Apr 1;62(1):112-21 - PubMed
  34. Am J Physiol. 1974 Jul;227(1):9-12 - PubMed
  35. Heart Rhythm. 2011 May;8(5):731-8 - PubMed
  36. J Physiol. 2016 Jul 15;594(14):3955-62 - PubMed
  37. Am J Physiol Heart Circ Physiol. 2013 Feb 15;304(4):H579-88 - PubMed
  38. J Physiol. 2013 Sep 15;591(18):4515-33 - PubMed
  39. J Physiol. 2016 Jul 15;594(14):3963-80 - PubMed
  40. Circ Res. 2004 Jul 9;95(1):76-83 - PubMed
  41. J Am Coll Cardiol. 1997 Feb;29(2):229-36 - PubMed
  42. Circ Heart Fail. 2009 Nov;2(6):692-9 - PubMed
  43. Cardiovasc Res. 1993 May;27(5):760-9 - PubMed
  44. Circulation. 1990 Jan;81(1):281-8 - PubMed
  45. Circulation. 1984 Jun;69(6):1182-9 - PubMed
  46. Front Physiol. 2019 Jan 28;10:16 - PubMed
  47. Heart Rhythm. 2013 May;10(5):751-7 - PubMed
  48. Am J Cardiol. 1986 Feb 1;57(4):299-309 - PubMed
  49. Neuron. 2002 Jan 3;33(1):15-22 - PubMed
  50. Circulation. 2005 Jul 12;112(2):164-70 - PubMed
  51. JCI Insight. 2020 Feb 13;5(3): - PubMed
  52. Hypertension. 2002 Jan;39(1):63-8 - PubMed
  53. Am J Physiol Heart Circ Physiol. 2015 Nov 15;309(10):H1740-52 - PubMed
  54. Brain Stimul. 2013 Jul;6(4):631-40 - PubMed
  55. Brain Res. 1975 Apr 11;87(2-3):239-46 - PubMed
  56. Circulation. 1974 Jan;49(1):86-97 - PubMed
  57. J Cardiovasc Transl Res. 2014 Apr;7(3):310-20 - PubMed
  58. J Physiol. 1953 Aug;121(2):341-59 - PubMed
  59. Anat Embryol (Berl). 1990;181(2):101-15 - PubMed
  60. Anat Rec. 1997 Feb;247(2):289-98 - PubMed
  61. Heart Fail Rev. 2011 Mar;16(2):171-8 - PubMed
  62. Eur J Neurol. 2015 Sep;22(9):1260-8 - PubMed
  63. Circ Res. 1966 Apr;18(4):416-28 - PubMed
  64. J Am Coll Cardiol. 2014 Jan 28;63(3):215-24 - PubMed
  65. J Physiol. 2016 Jan 15;594(2):321-41 - PubMed
  66. Nat Neurosci. 2005 Sep;8(9):1263-8 - PubMed
  67. Basic Res Cardiol. 2013 May;108(3):345 - PubMed
  68. Am J Physiol. 1990 Nov;259(5 Pt 2):H1365-73 - PubMed
  69. Circulation. 2004 Jan 6;109(1):120-4 - PubMed
  70. Auton Neurosci. 2009 Jan 28;145(1-2):55-62 - PubMed
  71. Am J Physiol. 1975 Jan;228(1):141-8 - PubMed
  72. Ergeb Physiol. 1963;52:74-156 - PubMed
  73. Int J Cardiol. 2017 Oct 1;244:229-234 - PubMed
  74. Am J Physiol Regul Integr Comp Physiol. 2008 Dec;295(6):R1926-33 - PubMed
  75. Sci Rep. 2020 Nov 2;10(1):18801 - PubMed
  76. J Mol Cell Cardiol. 2012 Mar;52(3):667-76 - PubMed
  77. Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R1066-75 - PubMed
  78. Eur Heart J. 2015 Feb 14;36(7):425-33 - PubMed
  79. Circ Res. 2000 Apr 14;86(7):816-21 - PubMed
  80. Physiol Rev. 1973 Jan;53(1):159-227 - PubMed
  81. Circ Res. 1990 Apr;66(4):900-12 - PubMed
  82. Circulation. 2019 Mar 5;139(10):e56-e528 - PubMed
  83. Am J Physiol. 1977 Dec;233(6):H655-9 - PubMed
  84. Am J Physiol Regul Integr Comp Physiol. 2004 Aug;287(2):R262-71 - PubMed
  85. Circ Res. 2015 Jun 5;116(12):2005-19 - PubMed
  86. Epilepsy Res. 2016 Oct;126:109-18 - PubMed
  87. Am J Physiol Regul Integr Comp Physiol. 2013 Dec 15;305(12):R1411-20 - PubMed
  88. J Cardiovasc Electrophysiol. 2013 Feb;24(2):188-95 - PubMed
  89. J Neural Eng. 2013 Apr;10(2):026003 - PubMed
  90. Int J Cardiol. 2021 Jan 15;323:175-178 - PubMed
  91. Am J Physiol Heart Circ Physiol. 2015 Oct;309(7):H1198-206 - PubMed
  92. Heart Rhythm. 2011 Mar;8(3):448-54 - PubMed
  93. N Engl J Med. 2008 May 8;358(19):2024-9 - PubMed
  94. Auton Neurosci. 2008 Aug 18;141(1-2):38-45 - PubMed
  95. Circ Res. 2014 May 23;114(11):1815-26 - PubMed
  96. Circulation. 1982 Oct;66(4):874-80 - PubMed
  97. J Clin Invest. 2007 Feb;117(2):289-96 - PubMed
  98. Cardiovasc Res. 1996 Sep;32(3):503-15 - PubMed
  99. Circ Heart Fail. 2019 Nov;12(11):e005879 - PubMed
  100. JCI Insight. 2020 Jun 4;5(11): - PubMed
  101. Am J Physiol Regul Integr Comp Physiol. 2000 Aug;279(2):R433-9 - PubMed
  102. Circulation. 2009 Oct 6;120(14):1380-9 - PubMed
  103. Braz J Med Biol Res. 2011 Sep;44(9):890-8 - PubMed
  104. Heart Rhythm. 2015 May;12(5):1027-35 - PubMed
  105. Circulation. 2020 Mar 3;141(9):e139-e596 - PubMed
  106. J Comp Neurol. 1980 Sep 15;193(2):435-65 - PubMed
  107. Am J Physiol Heart Circ Physiol. 2014 Sep 1;307(5):H722-31 - PubMed
  108. Lancet. 1998 Feb 14;351(9101):478-84 - PubMed
  109. Nat Rev Cardiol. 2014 Jun;11(6):346-53 - PubMed
  110. Eur J Cardiothorac Surg. 2014 Jun;45(6):1097-105 - PubMed
  111. J Physiol. 2016 Jul 15;594(14):3853-75 - PubMed
  112. Front Biosci (Landmark Ed). 2012 Jun 01;17:2419-32 - PubMed
  113. Am J Physiol. 1952 Sep;170(3):555-63 - PubMed
  114. Neurology. 2014 Jul 15;83(3):261-71 - PubMed
  115. Circulation. 2015 Jun 23;131(25):2185-93 - PubMed
  116. Auton Neurosci. 2000 Dec 20;85(1-3):1-17 - PubMed
  117. Peptides. 1990 Jul-Aug;11(4):753-61 - PubMed
  118. Am J Physiol Regul Integr Comp Physiol. 2012 Feb 1;302(3):R357-64 - PubMed
  119. J Am Coll Cardiol. 2016 Jul 12;68(2):149-58 - PubMed
  120. Neuroscience. 2009 Dec 15;164(3):1170-9 - PubMed
  121. JCI Insight. 2017 Aug 17;2(16): - PubMed
  122. Heart Fail Clin. 2012 Jan;8(1):87-99 - PubMed
  123. Cardiovasc Res. 2015 Feb 1;105(2):143-50 - PubMed
  124. Pharmacol Ther. 2006 Sep;111(3):808-35 - PubMed
  125. Ann N Y Acad Sci. 1990;611:166-74 - PubMed
  126. Auton Neurosci. 2014 May;182:4-14 - PubMed
  127. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239 - PubMed
  128. Am J Physiol. 1991 Mar;260(3 Pt 2):H713-21 - PubMed
  129. Am J Physiol. 1995 May;268(5 Pt 2):H1939-46 - PubMed
  130. J Comp Neurol. 1981 Oct 20;202(2):169-84 - PubMed
  131. Nat Commun. 2015 Feb 02;6:6235 - PubMed
  132. JCI Insight. 2019 Dec 5;4(23): - PubMed
  133. J Physiol. 1953 Dec 29;122(3):489-97 - PubMed
  134. J Am Coll Cardiol. 2009 Nov 3;54(19):1747-62 - PubMed
  135. Hypertension. 2014 Oct;64(4):745-55 - PubMed
  136. Auton Neurosci. 2017 Dec;208:57-65 - PubMed
  137. Heart Rhythm. 2014 Mar;11(3):360-6 - PubMed
  138. Exp Physiol. 2015 Feb 1;100(2):124-9 - PubMed
  139. N Engl J Med. 2014 Sep 11;371(11):993-1004 - PubMed
  140. JAMA Cardiol. 2020 Mar 1;5(3):318-325 - PubMed
  141. Circ Res. 1991 May;68(5):1471-81 - PubMed
  142. Circulation. 1993 Jan;87(1):240-6 - PubMed
  143. Am J Physiol. 1991 Jul;261(1 Pt 2):H63-9 - PubMed
  144. Ann N Y Acad Sci. 2001 Jun;940:59-73 - PubMed
  145. Circ Res. 1969 Nov;25(5):509-19 - PubMed
  146. ESC Heart Fail. 2020 Feb;7(1):75-83 - PubMed
  147. Lancet. 2001 May 5;357(9266):1385-90 - PubMed
  148. Am J Physiol Heart Circ Physiol. 2016 Nov 1;311(5):H1311-H1320 - PubMed
  149. Circ Arrhythm Electrophysiol. 2012 Oct;5(5):1010-116 - PubMed
  150. Heart Rhythm. 2009 Dec;6(12 Suppl):S26-34 - PubMed
  151. Am J Physiol. 1976 Sep;231(3):923-8 - PubMed
  152. JCI Insight. 2017 Sep 21;2(18): - PubMed
  153. Am J Physiol. 1993 Jul;265(1 Pt 2):H395-400 - PubMed
  154. Circulation. 2004 Apr 20;109(15):1826-33 - PubMed
  155. Card Fail Rev. 2018 Aug;4(2):92-98 - PubMed
  156. J Physiol. 2017 Nov 15;595(22):6887-6903 - PubMed
  157. J Card Fail. 2016 Aug;22(8):639-42 - PubMed
  158. J Cardiovasc Pharmacol. 2011 Nov;58(5):500-7 - PubMed
  159. Am J Physiol. 1997 Jun;272(6 Pt 2):H2843-51 - PubMed
  160. J Physiol. 2016 Jul 15;594(14):3911-54 - PubMed
  161. Ann Anat. 2014 Dec;196(6):430-40 - PubMed
  162. Prog Biophys Mol Biol. 2016 Jan;120(1-3):199-209 - PubMed
  163. Circulation. 1992 Jan;85(1 Suppl):I77-91 - PubMed
  164. Am J Physiol Heart Circ Physiol. 2016 May 15;310(10):H1349-59 - PubMed
  165. Ann Thorac Surg. 1990 Aug;50(2):251-6 - PubMed
  166. Am J Physiol. 1969 Sep;217(3):703-9 - PubMed
  167. Curr Heart Fail Rep. 2015 Aug;12(4):284-93 - PubMed
  168. ESC Heart Fail. 2018 Feb;5(1):95-100 - PubMed
  169. Cleve Clin J Med. 2011 Aug;78 Suppl 1:S24-9 - PubMed
  170. Circulation. 2008 Aug 19;118(8):863-71 - PubMed
  171. Am J Physiol. 1986 Oct;251(4 Pt 2):H764-73 - PubMed
  172. Am J Physiol. 1998 Apr;274(4):R939-49 - PubMed
  173. J Neurosci. 2016 Jan 13;36(2):479-88 - PubMed
  174. Eur J Heart Fail. 2008 Sep;10(9):884-91 - PubMed
  175. Circ Res. 1976 May;38(5):357-62 - PubMed

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