Skip to main content

Advertisement

SpringerLink
Log in

Voluntarily Produced Increases in Heart Rate Variability Modulate Autonomic Effects of Endotoxin Induced Systemic Inflammation: An Exploratory Study

  • Published:
Applied Psychophysiology and Biofeedback Aims and scope Submit manuscript

Abstract

Exposure of healthy people to lipopolysaccharide (LPS; endotoxin) produces a pro-inflammatory response, subjective symptoms, and decreased heart rate variability (HRV). Given the efficacy of HRV biofeedback (BF) for treating asthma, the large autonomic effects of HRV BF, and the link between vagus nerve activity and inflammation, we hypothesized that HRV BF would dampen the acute manifestations of systemic inflammation induced by LPS challenge. Healthy participants age 18-40 were randomly assigned to four-one-hour training sessions of either HRV BF (n = 6) or a control 15/min paced breathing condition (n = 5) prior to acute experimentally induced LPS exposure. Participants were coached to do the procedures for 10 min each at five hourly time points after LPS injection, and then 2 h later. Subjective symptoms, HRV parameters, and plasma cytokine levels were measured at each time point, 2 h afterward, and the following morning. Participants were able to perform the procedures both during four pre-exposure training sessions and while experiencing LPS-induced symptoms. The HRV BF group showed significant attenuation of the LPS-induced decline in HRV for the 6 h following LPS exposure, suggesting that HRV BF decreased autonomic dysfunction produced by LPS-induced inflammation. HRV BF also reduced symptoms of headache and eye sensitivity to light, but did not affect LPS-induced levels of pro-inflammatory cytokines or symptoms of nausea, muscle aches, or feverishness. Further evaluation of HRV BF appears to be warranted among patients with inflammatory conditions.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Akaike, H. A. (1974). A new look at the statistical model identification. IEEE Transactions on Automatic Control, 19, 716–723.

    Article  Google Scholar 

  • Alvarez, S. M., Katsamanis Karavidas, M., Coyle, S. M., Lu, S.-E., Macor, M., Oikawa, L. O., et al. (2007). Low-dose steroid alters in vivo endotoxin-induced systemic inflammation but does not influence autonomic dysfunction. Journal of Endotoxin Research, 13, 358–368.

    Article  PubMed  Google Scholar 

  • Appelhans, B. M., & Luecken, L. J. (2008). Heart rate variability and pain: Associations of two interrelated homeostatic processes. Biological Psychology, 77, 174–182.

    Article  PubMed  Google Scholar 

  • Berntson, G. G., Bigger, J. T., Eckberg, D. L., Grossman, P., Kaufman, P. G., Malik, M., et al. (1997). Heart rate variability: Origins, methods, and interpretive caveats. Psychophysiology, 34, 623–648.

    Article  PubMed  Google Scholar 

  • Bluzaite, I., Brazdzionyte, J., Zaliunas, R., Rickli, H., & Ammann, P. (2006). QT dispersion and heart rate variability in sudden death risk stratification in patients with ischemic heart disease. Medicina (Kaunas, Lithuania), 42, 450–454.

    Google Scholar 

  • Calvano, S. E., Xiao, W., Richards, D. R., Felciano, R. M., Baker, H. V., Cho, R. J., et al. (2005). A network-based analysis of systemic inflammation in humans. Nature, 437, 1032–1037.

    Article  PubMed  Google Scholar 

  • Carney, R. M., & Freedland, K. E. (2009). Depression and heart rate variability in patients with coronary heart disease. Cleveland Clinic Journal of Medicine, 76(Suppl 2), S13–S17.

    Google Scholar 

  • Chan, C. T. (2008). Heart rate variability in patients with end-stage renal disease: An emerging predictive tool for sudden cardiac death? Nephrology, Dialysis, Transplantation, 23, 3061–3062.

    Article  PubMed  Google Scholar 

  • Chen, J.-L., Chiu, H.-W., Tseng, Y.-J., & Chu, W.-C. (2006). Hyperthyroidism is characterized by both increased sympathetic and decreased vagal modulation of heart rate: Evidence from spectral analysis of heart rate variability. Clinical Endocrinology, 64, 611–616.

    Article  PubMed  Google Scholar 

  • Christensen, J. H. (2003). n-3 fatty acids and the risk of sudden cardiac death. Emphasis on heart rate variability. Danish Medical Bulletin, 50, 347–367.

    PubMed  Google Scholar 

  • Christou, D. D., & Seals, D. R. (2008). Decreased maximal heart rate with aging is related to reduced {beta}-adrenergic responsiveness but is largely explained by a reduction in intrinsic heart rate. Journal of Applied Physiology, 105, 24–29.

    Article  PubMed  Google Scholar 

  • Cooley, J. W., & Tukey J. W. (1965). An algorithm for machine calculation of complex Fourier series. Mathematics of Computation, 19, 297–301.

    Google Scholar 

  • Czura, C. J., & Tracey, K. J. (2005). Autonomic neural regulation of immunity. Journal of Internal Medicine, 257, 156–166.

    Article  PubMed  Google Scholar 

  • Drummond, P. D. (2006). Mechanisms of autonomic disturbance in the face during and between attacks of cluster headache. Cephalalgia, 26, 633–641.

    Article  PubMed  Google Scholar 

  • Eckberg, D. L. (2003). The human respiratory gate. Journal of Physiology, 548, 339–352.

    PubMed  Google Scholar 

  • Fazan, R., Jr., de Oliveira, M., da Silva, V. J. D., Joaquim, L. F., Montano, N., Porta, A., et al. (2005). Frequency-dependent baroreflex modulation of blood pressure and heart rate variability in conscious mice. American Journal of Physiology Heart & Circulatory Physiology, 289, H1968–H1975.

    Article  Google Scholar 

  • Giakoumaki, S. G., Hourdaki, E., Grinakis, V., Theou, K., & Bitsios, P. (2005). Effects of peripheral sympathetic blockade with dapiprazole on the fear-inhibited light reflex. Journal of Psychopharmacology, 19, 139–148.

    Article  PubMed  Google Scholar 

  • Godin, P. J., Fleisher, L. A., Eidsath, A., Vandivier, R. W., Preas, H. L., Banks, S. M., et al. (1996). Experimental human endotoxemia increases cardiac regularity: Results from a prospective, randomized, crossover trial. Critical Care Medicine, 24, 1117–1124.

    Article  PubMed  Google Scholar 

  • Grippo, A. J., & Johnson, A. K. (2002). Biological mechanisms in the relationship between depression and heart disease. Neuroscience and Biobehavioral Reviews, 26, 941–962.

    Article  PubMed  Google Scholar 

  • Grossman, P., Karemaker, J., & Wieling, W. (1991). Prediction of tonic parasympathetic cardiac control using respiratory sinus arrhythmia: The need for respiratory control. Psychophysiology, 28, 201–216.

    Article  PubMed  Google Scholar 

  • Guzzetti, S., Borroni, E., Garbelli, P. E., Ceriani, E., Della Bella, P., Montano, N., et al. (2005). Symbolic dynamics of heart rate variability: A probe to investigate cardiac autonomic modulation. Circulation, 112, 465–470.

    Article  PubMed  Google Scholar 

  • Halamek, J., Kara, T., Jurak, P., Soucek, M., Francis, D. P., Davies, L. C., et al. (2003). Variability of phase shift between blood pressure and heart rate fluctuations: A marker of short-term circulation control. Circulation, 108, 292–297.

    Article  PubMed  Google Scholar 

  • Jamner, L. D., & Tursky, B. (1987a). Discrimination between intensity and affective pain descriptors: A psychophysiological evaluation. Pain, 30, 271–283.

    Article  PubMed  Google Scholar 

  • Jamner, L. D., & Tursky, B. (1987b). Syndrome-specific descriptor profiling: A psychophysiological and psychophysical approach. Health Psychology, 6, 417–430.

    Article  PubMed  Google Scholar 

  • Jan, B. U., Coyle, S. M., Oikawa, L. O., Lu, S.-E., Calvano, S. E., Lehrer, P. M., et al. (2009). Influence of acute epinephrine infusion on endotoxin-induced parameters of heart rate variability: A randomized controlled trial. Annals of Surgery, 249, 750–756.

    Article  PubMed  Google Scholar 

  • Jankowska, E. A., Ponikowski, P., Piepoli, M. F., Banasiak, W., Anker, S. D., & Poole-Wilson, P. A. (2006). Autonomic imbalance and immune activation in chronic heart failure—Pathophysiological links. Cardiovascular Research, 70, 434–445.

    Article  PubMed  Google Scholar 

  • Karrow, N. A. (2006). Activation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system during inflammation and altered programming of the neuroendocrine-immune axis during fetal and neonatal development: Lessons learned from the model inflammagen, lipopolysaccharide. Brain, Behavior, & Immunity, 20, 144–158.

    Article  Google Scholar 

  • Kiba, T. (2006). Relationships between the autonomic nervous system, humoral factors and immune functions in the intestine. Digestion, 74, 215–227.

    PubMed  Google Scholar 

  • Lehrer, P. M. (2007). Biofeedback training to increase heart rate variability. In S. W. Lehrer, & R. L. Woolfolk (Eds.), Principles and practice of stress management, 3rd edn (pp. 227–248). New York: Guilford Press.

  • Lehrer, P., Carr, R. E., Smetankine, A., Vaschillo, E., Peper, E., Porges, S., et al. (1997). Respiratory sinus arrhythmia versus neck/trapezius EMG and incentive inspirometry biofeedback for asthma: A pilot study. Applied Psychophysiology & Biofeedback, 22, 95–109.

    Article  Google Scholar 

  • Lehrer, P., Smetankin, A., & Potapova, T. (2000a). Respiratory sinus arrhythmia biofeedback therapy for asthma: A report of 20 unmedicated pediatric cases using the Smetankin method. Applied Psychophysiology & Biofeedback, 25, 193–200.

    Article  Google Scholar 

  • Lehrer, P., Vaschillo, E., Lu, S.-E., Eckberg, D., Vaschillo, B., Scardella, A., et al. (2006). Heart rate variability biofeedback: Effects of age on heart rate variability, baroreflex gain, and asthma. Chest, 129, 278–284.

    Article  PubMed  Google Scholar 

  • Lehrer, P. M., Vaschillo, E., & Vaschillo, B. (2000b). Resonant frequency biofeedback training to increase cardiac variability: Rationale and manual for training. Applied Psychophysiology & Biofeedback, 25, 177–191.

    Article  Google Scholar 

  • Lehrer, P. M., Vaschillo, E., Vaschillo, B., Lu, S.-E., Eckberg, D. L., Edelberg, R., et al. (2003). Heart rate variability biofeedback increases baroreflex gain and peak expiratory flow. Psychosomatic Medicine, 65, 796–805.

    Article  PubMed  Google Scholar 

  • Lehrer, P. M., Vaschillo, E., Vaschillo, B., Lu, S.-E., Scardella, A., Siddique, M., et al. (2004). Biofeedback treatment for asthma. Chest, 126, 352–361.

    Article  PubMed  Google Scholar 

  • Lowry, S. F. (2005). Human endotoxemia: A model for mechanistic insight and therapeutic targeting. Shock, 24(Suppl 1), 94–100.

    Google Scholar 

  • Lowry, S. F. (2009). The stressed host response to infection: The disruptive signals and rhythms of systemic inflammation. Surgical Clinics of North America, 89, 311–326.

    Article  PubMed  Google Scholar 

  • Lowry, S. F., & Calvano, S. E. (2008). Challenges for modeling and interpreting the complex biology of severe injury and inflammation. Journal of Leukocyte Biology, 83, 553–557.

    Article  PubMed  Google Scholar 

  • Lupien, S. J., Ouellet-Morin, I., Hupbach, A., Tu, M. T., Buss, C., Walker, D., et al. (2006). Beyond the stress concept: Allostatic load—A developmental biological and cognitive perspective. Hoboken, NJ: Wiley.

    Google Scholar 

  • Mallen, E. A. H., Gilmartin, B., & Wolffsohn, J. S. (2005). Sympathetic innervation of ciliary muscle and oculomotor function in emmetropic and myopic young adults. Vision Research, 45, 1641–1651.

    Article  PubMed  Google Scholar 

  • McEwen, B., & Lasley, E. N. (2007). Allostatic load: When protection gives way to damage. Westport, CT: Praeger Publishers/Greenwood Publishing Group.

    Google Scholar 

  • McEwen, B. S., & Wingfield, J. C. (2003). The concept of allostasis in biology and biomedicine. Hormones and Behavior, 43, 2–15.

    Article  PubMed  Google Scholar 

  • Pinerua-Shuhaibar, L., Prieto-Rincon, D., Ferrer, A., Bonilla, E., Maixner, W., & Suarez-Roca, H. (1999). Reduced tolerance and cardiovascular response to ischemic pain in minor depression. Journal of Affective Disorders, 56, 119–126.

    Article  PubMed  Google Scholar 

  • Politano, L., Palladino, A., Nigro, G., Scutifero, M., & Cozza, V. (2008). Usefulness of heart rate variability as a predictor of sudden cardiac death in muscular dystrophies. Acta Myologica, 27, 114–122.

    PubMed  Google Scholar 

  • Porges, S. W. (1995). Orienting in a defensive world: Mammalian modifications of our evolutionary heritage. A polyvagal theory. Psychophysiology, 32, 301–318.

    Article  PubMed  Google Scholar 

  • Porges, S. W. (2001). The polyvagal theory: Phylogenetic substrates of a social nervous system. International Journal of Psychophysiology, 42, 123–146.

    Article  PubMed  Google Scholar 

  • Porges, S. W. (2007). The polyvagal perspective. Biological Psychology, 74, 116–143.

    Article  PubMed  Google Scholar 

  • Porges, S. W., Doussard-Roosevelt, J. A., Portales, A. L., & Greenspan, S. I. (1996). Infant regulation of the vagal “brake” predicts child behavior problems: A psychobiological model of social behavior. Developmental Psychobiology, 29, 697–712.

    Article  PubMed  Google Scholar 

  • Rainville, P., Bao, Q. V. H., & Chretien, P. (2005). Pain-related emotions modulate experimental pain perception and autonomic responses. Pain, 118, 306–318.

    Article  PubMed  Google Scholar 

  • Ritz, T., & Dahme, B. (2006). Implementation and interpretation of respiratory sinus arrhythmia measures in psychosomatic medicine: Practice against better evidence? Psychosomatic Medicine, 68, 617–627.

    Article  PubMed  Google Scholar 

  • Rosas-Ballina, M., Ochani, M., Parrish, W. R., Ochani, K., Harris, Y. T., Huston, J. M., et al. (2008). Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia. Proceedings of the National Academy of Sciences of the United States of America, 105, 11008–11013.

    Article  PubMed  Google Scholar 

  • Rubin, P. A., Chen, V. N., & Acquadro, M. A. (1996). Cluster headache presenting with orbital inflammation. Ophthalmic Surgery and Lasers, 27, 143–146.

    PubMed  Google Scholar 

  • Saeed, R. W., Varma, S., Giebelen, I. A., Florquin, S., Dallhuisen, J., Bruno, M. J., et al. (2005). Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. Journal of Experimental Medicine, 201, 1113–1123.

    Article  PubMed  Google Scholar 

  • Schuh-Hofer, S., Richter, M., Israel, H., Geworski, L., Villringer, A., Munz, D. L., et al. (2006). The use of radiolabelled human serum albumin and SPECT/MRI co-registration to study inflammation in the cavernous sinus of cluster headache patients. Cephalalgia, 26, 1115–1122.

    Article  PubMed  Google Scholar 

  • Sevoz-Couche, C., Comet, M. A., Bernard, J. F., Hamon, M., & Laguzzi, R. (2006). Cardiac baroreflex facilitation evoked by hypothalamus and prefrontal cortex stimulation: Role of the nucleus tractus solitarius 5-HT2A receptors. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 291, R1007–R1015.

    PubMed  Google Scholar 

  • Song, H.-S., & Lehrer, P. M. (2003). The effects of specific respiratory rates on heart rate and heart rate variability. Applied Psychophysiology & Biofeedback, 28, 13–23.

    Article  Google Scholar 

  • Tabata, M., Takeshima, T., Burioka, N., Nomura, T., Ishizaki, K., Mori, N., et al. (2000). Cosinor analysis of heart rate variability in ambulatory migraineurs. Headache, 40, 457–463.

    Article  PubMed  Google Scholar 

  • 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, clinical use. Circulation, 93, 1043–1065.

    Google Scholar 

  • Taylor, J. A., Carr, D. L., Myers, C. W., & Eckberg, D. L. (1998). Mechanisms underlying very-low-frequency RR-interval oscillations in humans. Circulation, 98, 547–555.

    PubMed  Google Scholar 

  • Tracey, K. J. (2007). Physiology and immunology of the cholinergic antiinflammatory pathway. Journal of Clinical Investigation, 117, 289–296.

    Article  PubMed  Google Scholar 

  • Tursky, B. (1974). Presidential address, 1973. Physical, physiological, and psychological factors that affect pain reaction to electric shock. Psychophysiology, 11, 95–112.

    Article  PubMed  Google Scholar 

  • van Westerloo, D. J., Giebelen, I. A. J., Florquin, S., Daalhuisen, J., Bruno, M. J., de Vos, A. F., et al. (2005). The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. Journal of Infectious Diseases, 191, 2138–2148.

    Article  PubMed  Google Scholar 

  • Van Zee, K. J., Coyle, S. M., Calvano, S. E., Oldenburg, H. S., Stiles, D. M., Pribble, J., et al. (1995). Influence of IL-1 receptor blockade on the human response to endotoxemia. Journal of Immunology, 154, 1499–1507.

    Google Scholar 

  • Van Zee, K. J., Moldawer, L. L., Oldenburg, H. S., Thompson, W. A., Stackpole, S. A., Montegut, W. J., et al. (1996). Protection against lethal Escherichia coli bacteremia in baboons (Papio anubis) by pretreatment with a 55-kDa TNF receptor (CD120a)-Ig fusion protein, Ro 45–2081. Journal of Immunology, 156, 2221–2230.

    Google Scholar 

  • Vaschillo, E., Lehrer, P., Rishe, N., & Konstantinov, M. (2002). Heart rate variability biofeedback as a method for assessing baroreflex function: A preliminary study of resonance in the cardiovascular system. Applied Psychophysiology & Biofeedback, 27, 1–27.

    Article  Google Scholar 

  • Vaschillo, E. G., Vaschillo, B., & Lehrer, P. M. (2006). Characteristics of resonance in heart rate variability stimulated by biofeedback. Applied Psychophysiology & Biofeedback, 31, 129–142.

    Article  Google Scholar 

  • Yende, S., Tuomanen, E. I., Wunderink, R., Kanaya, A., Newman, A. B., Harris, T., de Rekeneire, N., & Kritchevsky, S. B. (2005). Pre-infection systemic inflammatory markers and risk of hospitalization due to pneumonia. American Journal of Respiratory & Critical Care Medicine, 172, 1440–1446.

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Institutes of Health (NIGMS Grant R01 GM34695).

Author information

Authors and Affiliations

  1. Department of Psychiatry, UMDNJ-Robert Wood Johnson Medical School, 671 Hoes Lane, Piscataway, NJ, 08854, USA

    Paul Lehrer, Maria Katsamanis Karavidas, Shou-En Lu & Leo O. Oikawa

  2. Department of Biostatistics, UMDNJ-School of Public Health, New Brunswick, NJ, USA

    Shou-En Lu

  3. Division of Surgical Sciences, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA

    Susette M. Coyle, Marie Macor, Steve E. Calvano & Stephen F. Lowry

Authors
  1. Paul Lehrer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Katsamanis Karavidas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shou-En Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susette M. Coyle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Leo O. Oikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marie Macor
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Steve E. Calvano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stephen F. Lowry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul Lehrer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lehrer, P., Karavidas, M.K., Lu, SE. et al. Voluntarily Produced Increases in Heart Rate Variability Modulate Autonomic Effects of Endotoxin Induced Systemic Inflammation: An Exploratory Study. Appl Psychophysiol Biofeedback 35, 303–315 (2010). https://doi.org/10.1007/s10484-010-9139-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10484-010-9139-5

Keywords

Search

Navigation