Journal of Neural Transmission

, Volume 117, Issue 6, pp 729–735

The sympathetic-vagal balance against endotoxemia

  • Jian Huang
  • Yaoli Wang
  • Dongbo Jiang
  • Jian Zhou
  • Xiankai Huang
Basic Neurosciences, Genetics and Immunology - Original Article

Abstract

The goal of this study was to establish a convenient and effective approach to anti-inflammation treatment by rebalancing the sympathetic-vagal system via vagal nerve stimulation (VNS). We established an endotoxemia model in Sprague–Dawley rats using lipopolysaccharide (LPS) injection. Electrical discharges in the vagal system, including the nucleus tractus solitarii (NTS) and afferent and efferent cervical vagal nerves, were detected. The condition of sympathetic-vagal balance, presented as heart rate variability (HRV) and hepatic norepinephrine/acetylcholine (NE/ACh), was measured following endotoxemia with and without VNS. Discharges in afferent and efferent vagal nerves increased significantly following LPS injection compared with the basis level and corresponding time points in the control group. Discharges in the NTS also increased significantly following LPS injection. The HRV components, including normalized high frequency (HFnm), normalized low frequency (LFnm), LF/HF, and very low frequency (VLF), increased significantly following LPS injection. HFnm values in the LPS + VNS group increased significantly compared with the LPS group. Conversely, LFnm, LF/HF, and VLF in the LPS + VNS group decreased significantly compared with the LPS group. Hepatic NE and ACh significantly decreased within 6 h after LPS injection compared with the basal level and the control groups (P < 0.05). VNS did not significantly improve hepatic NE, but the ACh levels in the LPS + VNS group were higher than those in other groups. Sympathetic and vagal nervous systems are enhanced following endotoxemia. The overexcitation of the sympathetic system leads to sympathetic-vagal disequilibrium. The rebalance of the sympathetic and vagal system is crucial for critically ill patients.

Keywords

Sympathetic-vagal balance Endotoxemia Vagus nerve stimulation Heart rate variability Norepinephrine Acetylcholine 

References

  1. Alicea C, Belkowski S, Eisenstein TK, Adler MW, Rogers TJ (1996) Inhibition of primary murine macrophage cytokine production in vitro following treatment with the kappa-opioid agonist U50, 488H. J Neuroimmunol 64:83–90CrossRefPubMedGoogle Scholar
  2. Annane D, Trabold F, Sharshar T, Jarrin I, Blanc AS, Raphael JC, Gajdos P (1999) Inappropriate sympathetic activation at onset of septic shock—a spectral analysis approach. Am J Respir Crit Care Med 160:458–465PubMedGoogle Scholar
  3. Blalock JE (2002) Harnessing a neural-immune circuit to control inflammation and shock. J Exp Med 195:F25–F28CrossRefPubMedGoogle Scholar
  4. Bouma MG, Stad RK, van den Wildenberg F, Buurman WA (1994) Differential regulatory effects of adenosine on cytokine release by activated human monocytes. J Immunol 153:4159–4168PubMedGoogle Scholar
  5. Ek M, Engblom D, Saha S, Blomqvist A, Jakobsson PJ, Ericsson-Dahlstrand A (2001) Inflammatory response—pathway across the blood–brain barrier. Nature 410:430–431CrossRefPubMedGoogle Scholar
  6. Grogan EL, Morris JA, Norris PR, France DJ, Ozdas A, Stiles RA, Harris PA, Dawant BM, Speroff T (2004) Reduced heart rate volatility. Ann Surg 240:547–554CrossRefPubMedGoogle Scholar
  7. Huang J, Zhang NC, Zhou J, Yang ZH (2008) Effects of stimulation of intact vagus nerve on systemic inflammatory response in rats. Zhonghua Shao Shang Za Zhi 24:99–101PubMedGoogle Scholar
  8. Korach M, Sharshar T, Jarrin I, Fouillot JP, Raphael JC, Gajdos P, Annane D (2001) Cardiac variability in critically ill adults: influence of sepsis. Crit Care Med 29:1380–1385CrossRefPubMedGoogle Scholar
  9. Kunitake T, Ishiko N (1992) Power spectrum analysis of heart rate fluctuations and respiratory movements associated with cooling the human skin. J Auton Nerv Syst 38:45–55CrossRefPubMedGoogle Scholar
  10. Levin BE, Brown KL, Pawar G, Dunnmeynell A (1995) Widespread and lateralization effects of acute traumatic brain injury on norepinephrine turnover in the rat brain. Brain Res 674:307–313CrossRefPubMedGoogle Scholar
  11. Lo Giudice P, Careddu A, Magni G, Quagliata T, Pacifici L, Carminati P (2002) Autonomic neuropathy in streptozotocin diabetic rats: effect of acetyl-l-carnitine. Diabetes Res Clin Pract 56:173–180CrossRefPubMedGoogle Scholar
  12. Oberholzer A, Oberholzer C, Moldawer LL (2002) Inteyleukin-10: a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug. Crit Care Med 30:S58–S63CrossRefGoogle Scholar
  13. Pagani M, Montano N, Porta A, Malliani A, Abboud FM, Birkett C, Somers VK (1997) Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. Circulation 95:1441–1448PubMedGoogle Scholar
  14. Patil VK, David M (2009) Hepatotoxic potential of malathion in the freshwater teleost, Labeo rohita (Hamilton). Veterinarski Arhiv 79:179–188Google Scholar
  15. Pavlov VA, Ochani M, Yang LH, Gallowitsch-Puerta M, Ochani K, Lin XC, Levi J, Parrish WR, Rosas-Ballina M, Czura CJ, LaRosa GJ, Miller EJ, Tracey KJ, Al-Abed Y (2007) Selective alpha 7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med 35:1139–1144CrossRefPubMedGoogle Scholar
  16. Rosas-Ballina M, Ochani M, Parrish WR, Ochani K, Harris YT, Huston JM, Chavan S, Tracey KJ (2008) Splenic nerve is required for cholinergic anti inflammatory pathway control of TNF in endotoxemia. Proc Natl Acad Sci USA 105:11008–11013CrossRefPubMedGoogle Scholar
  17. Sackeim HA, Rush AJ, George MS, Marangell LB, Husain MM, Nahas Z, Johnson CR, Seidman S, Giller C, Haines S, Simpson RK, Goodman RR (2001) Vagus nerve stimulation (VNS (TM)) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology 25:713–728CrossRefPubMedGoogle Scholar
  18. Spengler RN, Chensue SW, Giacherio DA, Blenk N, Kunkel SL (1994) Endogenous norepinephrine regulates tumor necrosis factor-alpha production from macrophages in vitro. J Immunol 152:3024–3031PubMedGoogle Scholar
  19. Stauss HM (2003) Heart rate variability. Am J Physiol Regul Integr Comp Physiol 285:R927–R931PubMedGoogle Scholar
  20. Steinman L (2004) Elaborate interactions between the immune and nervous systems. Nat Immunol 5:575–581CrossRefPubMedGoogle Scholar
  21. Straub RH, Grum F, Strauch U, Capellino S, Bataille F, Bleich A, Falk W, Scholmerich J, Obermeier F (2008) Anti-inflammatory role of sympathetic nerves in chronic intestinal inflammation. Gut 57:911–921CrossRefPubMedGoogle Scholar
  22. Sun Y, Qin C, Foreman RD, Chen JD (2005) Intestinal electric stimulation modulates neuronal activity in the nucleus of the solitary tract in rats. Neurosci Lett 385:64–69CrossRefPubMedGoogle Scholar
  23. van Westerloo DJ, Giebelen IA, Florquin S, Daalhuisen J, Bruno MJ, de Vos AF, Tracey KJ, van der Poll T (2005) The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. J Infect Dis 191:2138–2148CrossRefPubMedGoogle Scholar
  24. Zdrenghea D, Sitar-Taut A, Pop D (2007) Comparison between heart rate variability and recovery in ischemic patients. Rom J Intern Med 45:171–175PubMedGoogle Scholar
  25. Zeitlinger M, Marsik C, Steiner I, Sauermann R, Seir K, Jilma B, Wagner O, Joukhadar C (2007) Immunomodulatory effects of fosfomycin in an endotoxin model in human blood. J Antimicrob Chemother 59:219–223CrossRefPubMedGoogle Scholar
  26. Zhou M, Yang SL, Koo DJ, Ornan DA, Chaudry IH, Wang P (2001) The role of Kupffer cell alpha(2)-adrenoceptors in norepinephrine-induced TNF-alpha production. Biochim Biophys Acta 1537:49–57PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Jian Huang
    • 1
  • Yaoli Wang
    • 1
  • Dongbo Jiang
    • 1
  • Jian Zhou
    • 1
  • Xiankai Huang
    • 2
  1. 1.Intensive Care Unit, Trauma center of PLA, Institute of Surgery Research, Daping HospitalThird Military Medical UniversityChongqingChina
  2. 2.Department of Trauma, Trauma center of PLA, Institute of Surgery Research, Daping HospitalThird Military Medical UniversityChongqingChina

Personalised recommendations