Skip to main content

Advertisement

Log in

Autonomic Dysfunctions in Patients with Inflammatory Bowel Disease in Clinical Remission

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Introduction and Objective The autonomic nervous system, especially the parasympathetic system, has been reported to modulate the immune response in chronic inflammatory disorders. Autonomic dysfunctions have been reported earlier in patients with inflammatory bowel disease; however, the results have been conflicting. We therefore evaluated autonomic functions in patients with inflammatory bowel disease (IBD) in clinical remission. Patients and Methods Heart rate variability, a marker of autonomic functions, which included time-domain, frequency-domain, and nonlinear indices (Poincaré plot) was assessed using Nevrokard, version 6.4.0 Slovenia, in 118 patients with IBD (ulcerative colitis [UC] 62, and Crohn’s disease [CD] 56) and 58 healthy controls. Results There was no difference in mean of R–R intervals in patients with UC, CD, and healthy controls. Frequency domain indices (absolute values of total power, high-frequency power, and low-frequency power) were lower in patients with UC and CD vs. healthy controls. High-frequency (HFnu) (expressed in normalized units) was significantly lower in UC compared to healthy controls. There was no significant difference in the low-frequency (LFnu) and LF/HF ratio in UC, CD, and healthy controls. Amongst the Poincaré plot indices, while standard deviation of the instantaneous R–R interval variability (SD1nu) was lower in UC and CD vs. healthy controls, there was no significant difference in the long-term R–R interval variability (SD2nu). Conclusions Patients with inflammatory bowel disease have lower autonomic functions. Patients with UC have significantly lower parasympathetic function in comparison to those with CD and healthy controls. These autonomic dysfunctions in patients with IBD may have a bearing on the pathogenesis of IBD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ANS:

Autonomic nervous system

SNS:

Sympathetic nervous system

PNS:

Parasympathetic nervous system

ENS:

Enteric nervous system

HRV:

Heart rate variability

IBD:

Inflammatory bowel disease

UC:

Ulcerative colitis

CD:

Crohn’s disease

BP:

Blood pressure

SDNN:

Standard deviation of differences between adjacent R–R intervals

COV:

Coefficient of variance

SDSD:

Standard deviation of differences between adjacent R–R intervals

rMSSD:

Root mean square of successive differences between adjacent R–R intervals

pNN50:

Percentage of number of R–R intervals with differences ≥50 ms

nu:

Normalized units

HF:

High frequency

LF:

Low frequency

VLF:

Very low frequency

TP:

Total power

SD:

Standard deviation

SBP:

Systolic blood pressure

DBP:

Diastolic blood pressure

IL:

Interleukin

HR:

Heart rate

ECG:

Electrocardiogram

References

  1. Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES (2000) The sympathetic nerve—an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 52:595–638

    PubMed  CAS  Google Scholar 

  2. Matsunaga K, Klein TW, Friedman H, Yamamoto Y (2001) Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection by nicotine. J Immunol 167:6518–6524

    PubMed  CAS  Google Scholar 

  3. McCafferty DM, Wallace JL, Sharkey KA (1997) Effects of chemical sympathectomy and sensory nerve ablation on experimental colitis in the rat. Am J Physiol 272:G272–G280

    PubMed  CAS  Google Scholar 

  4. Furlan R, Ardizzone S, Palazzolo L, Rimoldi A, Perego F, Barbic F et al (2006) Sympathetic overactivity in active ulcerative colitis: effects of clonidine. Am J Physiol Regul Integr Comp Physiol 290:R224–R232. doi:10.1152/ajpregu.00442.2005

    PubMed  CAS  Google Scholar 

  5. Eliakim R, Karmeli F, Rachmilewitz D, Cohen P, Fich A (1998) Effect of chronic nicotine administration on trinitrobenzene sulphonic acid-induced colitis. Eur J Gastroenterol Hepatol 10:1013–1019. doi:10.1097/00042737-199812000-00006

    Article  PubMed  CAS  Google Scholar 

  6. Bernik TR, Friedman SG, Ochani M, DiRaimo R, Ulloa L, Yang H et al (2002) Pharmacological stimulation of the cholinergic antiinflammatory pathway. J Exp Med 195:781–788. doi:10.1084/jem.20011714

    Article  PubMed  CAS  Google Scholar 

  7. Ghia JE, Blennerhassett P, Kumar-Ondiveeran H, Verdu EF, Collins SM (2006) The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model. Gastroenterology 131:1122–1130. doi:10.1053/j.gastro.2006.08.016

    Article  PubMed  Google Scholar 

  8. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996) Heart rate variability: standards of measurement physiological interpretation and clinical use. Circulation 93:1043–1065

    Google Scholar 

  9. Mittal CM, Wig N, Mishra S, Deepak KK (2004) Heart rate variability in human immunodeficiency virus-positive individuals. Int J Cardiol 94:1–6. doi:10.1016/j.ijcard.2003.02.002

    Article  PubMed  Google Scholar 

  10. Evrengul H, Dursunoglu D, Cobankara V, Polat B, Seleci D, Kabukçu S et al (2004) Heart rate variability in patients with rheumatoid arthritis. Rheumatol Int 24:198–202. doi:10.1007/s00296-003-0357-5

    Article  PubMed  Google Scholar 

  11. Wranicz JK, Cygankiewicz I, Zielinska M, Woźniacka A, Sysa-Jedrzejowska A (2001) Non-invasive cardiac evaluation in patients with systemic lupus erythematosus. J Med 32:195–206

    PubMed  CAS  Google Scholar 

  12. Tillisch K, Mayer EA, Labus JS, Stains J, Chang L, Naliboff BD (2005) Sex specific alteration in autonomic functions patients with irritable bowel syndrome. Gut 54:1396–1401. doi:10.1136/gut.2004.058685

    Article  PubMed  CAS  Google Scholar 

  13. Ganguli SC, Kamath MV, Redmond K, Chen Y, Irvine EJ, Collins SM et al (2007) A comparison of autonomic function in patients with inflammatory bowel disease and in healthy controls. Neurogastroenterol Motil 12:961–967

    Google Scholar 

  14. Maule S, Pierangeli G, Cevoli S, Grimaldi D, Gionchetti P, Barbara G et al (2007) Sympathetic hyperactivity in patients with ulcerative colitis. Clin Auton Res 4:217–220. doi:10.1007/s10286-007-0425-0

    Article  Google Scholar 

  15. Coruzzi P, Castiglioni P, Parati G, Brambilla V, Brambilla L, Gualerzi M et al (2007) Autonomic cardiovascular regulation in quiescent ulcerative colitis and Crohn’s disease. Eur J Clin Invest 37:964–970. doi:10.1111/j.1365-2362.2007.01887.x

    Article  PubMed  CAS  Google Scholar 

  16. Mouzas IA, Pallis AG, Kochiadakis GE, Marketou M, Chlouverakis GI, Mellisas J et al (2002) Autonomic imbalance during the day in patients with inflammatory bowel disease in remission. Evidence from spectral analysis of heart rate variability over 24 h. Dig Liver Dis 34:775–780. doi:10.1016/S1590-8658(02)80070-6

    Article  PubMed  CAS  Google Scholar 

  17. Straub RH, Antoniou E, Zeuner M, Gross V, Schölmerich J, Andus T (1997) Association of autonomic nervous hyperreflexia and systemic inflammation in patients with Crohn’s disease and ulcerative colitis. J Neuroimmunol 80:149–157. doi:10.1016/S0165-5728(97)00150-1

    Article  PubMed  CAS  Google Scholar 

  18. Benjamin J, Makharia GK, Ahuja V, Kalaivani M, Joshi YK (2008) Intestinal permeability and its association with the patients’ and disease characteristics in Crohn’s disease. World J Gastroenterol 14(9):1399–1405. doi:10.3748/wjg.14.1399

    Article  PubMed  Google Scholar 

  19. Makharia GK, Sachdev V, Gupta R, Lal S, Pandey RM (2007) Anti-Saccharomyces cerevisiae antibody does not differentiate between Crohn’s disease and intestinal tuberculosis. Dig Dis Sci 52(1):33–39. doi:10.1007/s10620-006-9527-0

    Article  PubMed  Google Scholar 

  20. Truelove SC, Witts LJ (1955) Cortisone in ulcerative colitis; final report on a therapeutic trial. BMJ 2:1041–1048

    Article  PubMed  CAS  Google Scholar 

  21. Best WR, Becket JM, Singleton JW, Fern F Jr (1976) Development of a Crohn’s disease activity index. National Cooperative Crohn’s disease study. Gastroenterology 70(3):439–444

    PubMed  CAS  Google Scholar 

  22. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR et al (2005) Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 19(Suppl A):5–36

    Google Scholar 

  23. Tulppo MP, Makikallio TH, Takala TE, Seppänen T, Huikuri HV (1996) Quantitative beat-to-beat analysis of heart rate dynamics during exercise. Am J Physiol 271:H244–H252

    PubMed  CAS  Google Scholar 

  24. Altman DG (1991) Practical statistics for medical research, 1st edn. Chapman & Hall/CRC, London

    Google Scholar 

  25. Ghia JE, Blennerhassett P, El-Sharkawy RT, Collins SM (2007) The protective effect of the vagus nerve in a murine model of chronic relapsing colitis. Am J Physiol Gastrointest Liver Physiol 293(4):G711–G718. doi:10.1152/ajpgi.00240.2007

    Article  PubMed  CAS  Google Scholar 

  26. Tracey (2002) The inflammatory reflex. Nature 420:853–859. doi:10.1038/nature01321

    Article  PubMed  CAS  Google Scholar 

  27. De Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ et al (2005) Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol 6:844–851. doi:10.1038/ni1229

    Article  PubMed  CAS  Google Scholar 

  28. Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S et al (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421:384–388. doi:10.1038/nature01339

    Article  PubMed  CAS  Google Scholar 

  29. Ohlsson B, Sundkvist G, Lindgren S (2007) Subclinical sympathetic neuropathy appears early in the course of Crohn’s disease. BMC Gastroenterol 7:33. doi:10.1186/1471-230X-7-33

    Article  PubMed  Google Scholar 

  30. Kyösola K, Penttilä O, Salaspuro M (1977) Rectal mucosal adrenergic innervation and enterochromaffin cells in ulcerative colitis and irritable colon. Scand J Gastroenterol 12(3):363–367

    Article  PubMed  Google Scholar 

  31. Dvorak AM, Silen W (1985) Differentiation between Crohn’s disease and other inflammatory conditions by electron microscopy. Ann Surg 201(1):53–63. doi:10.1097/00000658-198501000-00008

    Article  PubMed  CAS  Google Scholar 

  32. Magro F, Vieira-Coelho MA, Fraga S, Serrão MP, Veloso FT, Ribeiro T et al (2002) Impaired synthesis or cellular storage of norepinephrine, dopamine, and 5-hydroxytryptamine in human inflammatory bowel disease. Dig Dis Sci 47(1):216–224. doi:10.1023/A:1013256629600

    Article  PubMed  CAS  Google Scholar 

  33. Penttilä O, Kyösola K, Klinge E, Ahonen A, Tallqvist G (1975) Studies of rectal mucosal catecholamines in ulcerative colitis. Ann Clin Res 7(1):32–36

    PubMed  Google Scholar 

  34. Ewing DJ, Campbell IW, Clarke BF (1980) The natural history of diabetic autonomic neuropathy. Q J Med 49:95–108

    PubMed  CAS  Google Scholar 

  35. Pagani M, Montano N, Porta A, Malliani A, Narkiewicz K, Abboud FM et al (1997) Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. Circulation 95:1441–1448

    PubMed  CAS  Google Scholar 

  36. Howorka K, Pumprla J, Schabmann A (1998) Optimal parameters of short-term heart rate spectrogram for routine evaluation of diabetic cardiovascular autonomic neuropathy. J Auton Nerv Syst 69:164–172. doi:10.1016/S0165-1838(98)00015-0

    Article  PubMed  CAS  Google Scholar 

  37. Emmanuel AV, Kamm MA (2000) Laser Doppler flowmetry as a measure of extrinsic colonic innervations in functional bowel disease. Gut 46:212–217. doi:10.1136/gut.46.2.212

    Article  PubMed  CAS  Google Scholar 

  38. Geissler A, Andus T, Roth M, Kullmann F, Caesar I, Held P et al (1995) Focal white matter lesions in the brain of patients with inflammatory bowel disease. Lancet 345:897–898. doi:10.1016/S0140-6736(95)90013-6

    Article  PubMed  CAS  Google Scholar 

  39. Druschky A, Heckmann JG, Druschky K, Huk WJ, Erbguth F, Neundörfer B (2002) Severe neurological complications of ulcerative colitis. J Clin Neurosci 9:84–86. doi:10.1054/jocn.2001.0972

    Article  PubMed  CAS  Google Scholar 

  40. Nemoto H, Iguchi H, Ichikawa Y, Wakata N, Urinary T (2004) Ulcerative colitis presenting as sensorineural deafness, brainstem encephalopathy, and white matter lesions. Neurologist 10:165–168. doi:10.1097/01.nrl.0000126590.16002.39

    Article  PubMed  Google Scholar 

  41. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR et al (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462. doi:10.1038/35013070

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The study was supported by the grant from the Central Council for Research in Yoga and Naturopathy (CCRYN), New Delhi, India.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kishore Kumar Deepak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sharma, P., Makharia, G.K., Ahuja, V. et al. Autonomic Dysfunctions in Patients with Inflammatory Bowel Disease in Clinical Remission. Dig Dis Sci 54, 853–861 (2009). https://doi.org/10.1007/s10620-008-0424-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-008-0424-6

Keywords

Navigation