Clinical Autonomic Research

, Volume 20, Issue 4, pp 229–233 | Cite as

Does an acute inflammatory response temporarily attenuate parasympathetic reactivation?

  • Sae Young Jae
  • Kevin S. Heffernan
  • Soo-Hyun Park
  • Sun-Hae Jung
  • Eun Sun Yoon
  • Euy Jin Kim
  • Eui Soo Ahn
  • Bo Fernhall
Research Article



Although observational studies suggest that inflammatory markers are associated with autonomic nervous system function, the causal relationship of this is not clear. We tested the hypothesis that acute inflammation will temporarily attenuate vagal reactivation as measured by heart rate recovery after exercise.


In this double-blind randomized study, 24 healthy subjects were assigned to receive either an influenza vaccine (n = 15) as a model to generate a systemic inflammatory response or a sham vaccine (n = 9). Heart rate recovery after exercise testing was used as an index of parasympathetic nervous function and was calculated as the difference between maximal heart rate during the test and heart rate 1 and 2 min after cessation of exercise. Both blood analysis and treadmill exercise stress tests were conducted before and 48 h after each vaccination.


Inflammatory marker, log C-reactive protein (1.9 ± 1.2 to 2.8 ± 1.4, p < 0.05) was significantly increased after the influenza vaccine. Heart rate recovery 1 was significantly attenuated 48 h after the influenza vaccination (23.4 ± 6.4 to 20.5 ± 4.9, p < 0.05) but not sham vaccination.


These findings show that acute inflammation is associated with a temporary deterioration in cardiac autonomic nervous system function in healthy subjects.


Inflammation Autonomic nervous system Heart rate recovery C-reactive protein 



This work was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF-2009-32A-G00050).


  1. 1.
    Ando M, Katare RG, Kakinuma Y, Zhang D, Yamasaki F, Muramoto K, Sato T (2005) Efferent vagal nerve stimulation protects heart against ischemia-induced arrhythmias by preserving connexin43 protein. Circulation 112:164–170CrossRefPubMedGoogle Scholar
  2. 2.
    Bolton C, Thompson J, Bernardi L, Voll C, Young B (2007) The cardiac R-R variation and sympathetic skin response in the intensive care unit. Can J Neurol Sci 34:313–315PubMedGoogle Scholar
  3. 3.
    Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462CrossRefPubMedGoogle Scholar
  4. 4.
    Chikanza IC (1999) Neuroendocrine immune features of pediatric inflammatory rheumatic diseases. Ann NY Acad Sci 876:71–80CrossRefPubMedGoogle Scholar
  5. 5.
    Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS (1999) Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med 341:1351–1357CrossRefPubMedGoogle Scholar
  6. 6.
    Davis MM, Taubert K, Benin AL, Brown DW, Mensah GA, Baddour LM, Dunbar S, Krumholz HM (2006) Influenza vaccination as secondary prevention for cardiovascular disease: a science advisory from the American Heart Association/American College of Cardiology. Circulation 114:1549–1553CrossRefPubMedGoogle Scholar
  7. 7.
    Fairchild KD, Saucerman JJ, Raynor LL, Sivak JA, Xiao Y, Lake DE, Moorman JR (2009) Endotoxin depresses heart rate variability in mice: cytokine and steroid effects. Am J Physiol Regul Integr Comp Physiol 297:1019–1027Google Scholar
  8. 8.
    Haensel A, Mills PJ, Nelesen RA, Ziegler MG, Dimsdale JE (2008) The relationship between heart rate variability and inflammatory markers in cardiovascular diseases. Psychoneuroendocrinology 33:1305–1312CrossRefPubMedGoogle Scholar
  9. 9.
    Imai K, Sato H, Hori M, Kusuoka H, Ozaki H, Yokoyama H, Takeda H, Inoue M, Kamada T (1994) Vagally mediated heart rate recovery after exercise is accelerated in athletes but blunted in patients with chronic heart failure. J Am Coll Cardiol 24:1529–1535CrossRefPubMedGoogle Scholar
  10. 10.
    Jae SY, Ahn ES, Heffernan KS, Woods JA, Lee MK, Park WH, Fernhall B (2007) Relation of heart rate recovery after exercise to C-reactive protein and white blood cell count. Am J Cardiol 99:707–710CrossRefPubMedGoogle Scholar
  11. 11.
    Juttler E, Tarabin V, Schwaninger M (2002) Interleukin-6: a possible neuromodulator induced by neuronal activity. Neuroscientist 8:268–275PubMedGoogle Scholar
  12. 12.
    Kannankeril PJ, Le FK, Kadish AH, Goldberger JJ (2004) Parasympathetic effects on heart rate recovery after exercise. J Investig Med 52:394–401CrossRefPubMedGoogle Scholar
  13. 13.
    Kleiger RE, Miller JP, Bigger JT, Moss AJ (1987) Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59:256–262CrossRefPubMedGoogle Scholar
  14. 14.
    Liuba P, Aburawi EH, Pesonen E, Andersson S, Truedsson L, Yla-Herttuala S, Holmberg L (2007) Residual adverse changes in arterial endothelial function and LDL oxidation after a mild systemic inflammation induced by influenza vaccination. Ann Med 39:392–399CrossRefPubMedGoogle Scholar
  15. 15.
    Meier CR, Jick SS, Derby LE, Vasilakis C, Jick H (1998) Acute respiratory-tract infections and risk of first-time acute myocardial infarction. Lancet 351:1467–1471CrossRefPubMedGoogle Scholar
  16. 16.
    Pavlov VA, Tracey KJ (2005) The cholinergic anti-inflammatory pathway. Brain Behav Immun 19:493–499CrossRefPubMedGoogle Scholar
  17. 17.
    Pluess TT, Hayoz D, Berger MM, Tappy L, Revelly JP, Michaeli B, Carpentier YA, Chiolero RL (2007) Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects. Intensive Care Med 33:789–797CrossRefPubMedGoogle Scholar
  18. 18.
    Posthouwer D, Voorbij HA, Grobbee DE, Numans ME, van der Born JG (2004) Influenza and pneumococcal vaccination as a model to assess C-reactive protein response to mild inflammation. Vaccine 23:362–365CrossRefPubMedGoogle Scholar
  19. 19.
    Sayk F, Vietheer A, Schaaf B, Wellhoener P, Weitz G, Lehnert H, Dodt C (2008) Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans. Am J Physiol Regul Integr Comp Physiol 295:891–898Google Scholar
  20. 20.
    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(1 Suppl):177–191Google Scholar
  21. 21.
    Sloan RP, McCreath H, Tracey KJ, Sidney S, Liu K, Seeman T (2007) RR interval variability is inversely related to inflammatory markers: the CARDIA study. Mol Med 13:178–184PubMedGoogle Scholar
  22. 22.
    Smeeth L, Casas JP, Hingorani AD (2007) The role of infection in cardiovascular disease: more support but many questions remain. Eur Heart J 28:1178–1179CrossRefPubMedGoogle Scholar
  23. 23.
    Smith LL, Kukielka M, Billman GE (2005) Heart rate recovery after exercise: a predictor of ventricular fibrillation susceptibility after myocardial infarction. Am J Physiol Heart Circ Physiol 288:1763–1769CrossRefGoogle Scholar
  24. 24.
    Stojanovich L, Milovanovich B, de Luke SR, Popovich-Kuzmanovich D, Bisenich V, Djikanovich B, Randjelovich T, Krotin M (2007) Cardiovascular autonomic dysfunction in systemic lupus, rheumatoid arthritis, primary Sjögren syndrome and other autoimmune diseases. Lupus 16:181–185PubMedGoogle Scholar
  25. 25.
    Tillett HE, Smith JW, Gooch CD (1983) Excess deaths attributable to influenza in England and Wales: age at death and certified cause. Int J Epidemiol 12:344–352CrossRefPubMedGoogle Scholar
  26. 26.
    Tracey KJ (2002) The inflammatory reflex. Nature 420:853–859CrossRefPubMedGoogle Scholar
  27. 27.
    Tsai MY, Hanson NQ, Straka RJ, Hoke TR, Ordovas JM, Peacock JM, Arends VL, Arnett DK (2005) Effect of influenza vaccine on markers of inflammation and lipid profile. J Lab Clin Med 145:323–327CrossRefPubMedGoogle Scholar
  28. 28.
    Tsuji H, Larson MG, Venditti FJ, Manders ES, Evans JC, Feldman CL, Levy D (1996) Impact of heart rate variability on risk for cardiac events: the Framingham Heart Study. Circulation 94:2850–2855PubMedGoogle Scholar
  29. 29.
    Van der Sande MA, Van Asten L, Straus SM, van der Schim Loeff MF, Wallinga J, Conyn-van Spaendonck MA (2008) Sudden deaths following influenza vaccination: can this be expected? Vaccine 26:379–382CrossRefPubMedGoogle Scholar
  30. 30.
    Zipes DP (2008) Heart-brain interactions in cardiac arrhythmias: role of the autonomic nervous system. Cleve Clin J Med 75:s94–s96CrossRefPubMedGoogle Scholar
  31. 31.
    Vieira VJ, Valentine RJ, McAuley E, Evans E, Woods JA (2007) Independent relationship between heart rate recovery and C-reactive protein in older adults. J Am Geriatr Soc 55:747–751CrossRefPubMedGoogle Scholar
  32. 32.
    Tang YD, Dewland TA, Wencker D, Katz SD (2009) Post-exercise heart rate recovery independently predicts mortality risk in patients with chronic heart failure. J Card Fail 15:850–855CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Sae Young Jae
    • 1
  • Kevin S. Heffernan
    • 2
  • Soo-Hyun Park
    • 3
  • Sun-Hae Jung
    • 3
  • Eun Sun Yoon
    • 1
  • Euy Jin Kim
    • 1
  • Eui Soo Ahn
    • 3
  • Bo Fernhall
    • 4
  1. 1.Department of Sports Informatics, The Health and Integrative Physiology LaboratoryUniversity of SeoulSeoulSouth Korea
  2. 2.Division of CardiologyTufts Medical CenterBostonUSA
  3. 3.Department of Sports ScienceSungkyunkwan UniversitySeoulSouth Korea
  4. 4.Department of Kinesiology and Community HealthUniversity of IllinoisUrbana-ChampaignUSA

Personalised recommendations