Advertisement

The Consequences of Cardiac Autonomic Dysfunction in Multiple Organ Dysfunction Syndrome

  • H. Schmidt
  • U. Müller-Werdan
  • K. Werdan
Conference paper

Abstract

The development of multiple organ dysfunction syndrome (MODS) is characterized by activation of innate immunity, resulting in an inappropriate release of inflammatory mediators leading to cellular damage in parenchymal organs and to inflammatory, metabolic, and neuroendocrine disturbances [1]. There is increasing evidence that autonomie dysfunction may contribute substantially to the development of MODS since continuous communication between all vital organs through autonomic nervous system signals is a fundamental feature in healthy humans [2, 3]. An ‘uncoupling’ of these neurally mediated organ interactions in MODS and sepsis may potentially alter neural reflexes and thus cause a disruption of appropriate interorgan communication, thereby advancing single organ dysfunction into MODS. There may also be a diminished reactivity of the organ to reflex stimuli. Taking into consideration the interference of the mediators and toxins with cardiac cellular signal transduction, blunted or dysfunctional cellular responses possibly contribute to decreased reflex responses of the target organ, leading to an impairment in the autonomic balance of the heart.

Keywords

Heart Rate Variability Statin Therapy Angiotensin Converting Enzyme Inhibitor Multiple Organ Dysfunction Syndrome Baroreflex Sensitivity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Godin PJ, Buchmann TG (1996) Uncoupling of biological oscillators. A complementary hypothesis concerning the pathogenesis of multiple organ dysfunction syndrome. Crit Care Med 24: 1107–1116PubMedCrossRefGoogle Scholar
  2. 2.
    Schmidt H, Müller-Werdan U, Hoffmann T, et al (2005) Autonomic dysfunction predicts mortality in patients with multiple organ dysfunction syndrome of different age groups. Crit Care Med 33: 1994–2002PubMedCrossRefGoogle Scholar
  3. 3.
    Schmidt H, Moyer D, Hennen R, et al (2007) Autonomic dysfunction predicts both one-and two-month mortality in middle-aged patients with multiple organ dysfunction syndrome. Crit Care Med (in press)Google Scholar
  4. 4.
    Tracey KJ (2002) The inflammatory reflex. Nature 420: 853–859PubMedCrossRefGoogle Scholar
  5. 5.
    Borovikova LV, Ivanova S, Zhang M, et al (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405: 458–462PubMedCrossRefGoogle Scholar
  6. 6.
    Libert C (2003) A nervous connection. Nature 421: 328–329PubMedCrossRefGoogle Scholar
  7. 7.
    Wang H, Yu M, Ochani M, et al (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421: 384–388PubMedCrossRefGoogle Scholar
  8. 8.
    Tracey KJ (2007) Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest 117: 289–296PubMedCrossRefGoogle Scholar
  9. 9.
    Wang H, Liao H, Ochani M, et al (2004) Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 10: 1216–1221PubMedCrossRefGoogle Scholar
  10. 10.
    Saeed RW, Varma S, Peng-Nemeroff, T et al (2005) Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med 201: 1113–1123PubMedCrossRefGoogle Scholar
  11. 11.
    Pavlov VA, Ochani M, Gallowitsch-Puerta M, et al (2006) Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc Natl Acad Sci USA 103: 5219–5223PubMedCrossRefGoogle Scholar
  12. 12.
    Abboud FM, Thames MD (1983) Interaction of cardiovascular reflexes in circulatory control. In: Sheperd JT, Abboud FM, Geiger SR (eds) Handbook of Physiology. Section 2: The Cardiovascular System. Vol. III, Chapter 19. American Physiological Society, Bethesda, pp 675–752Google Scholar
  13. 13.
    Eyzaguirre C, Fitzgerald RS, Lahiri S, Zapata P: Arterial chemoreceptors. In: Sheperd JT, Abboud FM, Geiger SR (eds) Handbook of Physiology. Section 2: The Cardiovascular System. Vol. III, Chapter 16. American Physiological Society, Bethesda, pp 557–562Google Scholar
  14. 14.
    Godin PJ, Fleisher LA, Eidsath A, et al (1996) Experimental human endotoxemia increases cardiac regularity: results from a prospective, randomized crossover trial. Crit Care Med 24: 1117–1124PubMedCrossRefGoogle Scholar
  15. 15.
    Schmidt H, Müller-Werdan U, Saworski J, Kuhn C, Heinroth C, Werdan K (1999) Beating rate variability of cardiomyocytes is narrowed by LPS but not by TNF-α? Intensive Care Med 25(suppl 1): 59 (abst)Google Scholar
  16. 16.
    Zorn-Pauly K, Pelzmann B, Lang P, et al (2007) Endotoxin impairs the human pacemaker current If. Shock [Epub ahead of print]Google Scholar
  17. 17.
    Merx MW, Liehn EA, Janssens U, et al (2004) HMG-CoA reductase inhibitor simvastatin profoundly improves survival in a murine model of sepsis. Circulation 109: 2560–2565PubMedCrossRefGoogle Scholar
  18. 18.
    Pruefer D, Makowski J, Schnell M, et al (2002) Simvastatin inhibits inflammatory properties of Staphylococcus aureus alpha-toxin. Circulation 106: 2104–2110PubMedCrossRefGoogle Scholar
  19. 19.
    Almog Y, Shefer A, Novack V, et al (2004) Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 110: 880–885PubMedCrossRefGoogle Scholar
  20. 20.
    Kruger P, Fitzsimmons K, Cook D, Jones M, Nimmo G (2006) Statin therapy is associated with fewer deaths in patients with bacteraemia. Intensive Care Med 32: 75–77PubMedCrossRefGoogle Scholar
  21. 21.
    Schmidt H, Hennen R, Keller A, et al (2006) Association of statin therapy and increased survival in patients with multiorgan dysfunction syndrome. Intensive Care Med 32: 1248–1251PubMedCrossRefGoogle Scholar
  22. 22.
    Parati G, Mutti E, Frattola A, et al (1994) Beta-adrenergic blocking treatment and 24-hour baroreflex sensitivity in essential hypertensive patients. Hypertension 23: 992–996PubMedGoogle Scholar
  23. 23.
    Agostoni P, Contini M, Magini A et al. (2006) Carvedilol reduces exercise-induced hyperventilation: A benefit in normoxia and a problem with hypoxia. Eur J Heart Fail 8: 729–735PubMedCrossRefGoogle Scholar
  24. 24.
    The CONSENSUS Trial Study Group (1987) Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 316: 1429–1435Google Scholar
  25. 25.
    The SOLVD Investigators. (1991) Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 325: 293–302Google Scholar
  26. 26.
    Ferrario CM, Strawn WB (2006) Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease. Am J Cardiol 98: 121–128PubMedCrossRefGoogle Scholar
  27. 27.
    Routledge HC, Chowdhary S, Townend JN (2002) Heart rate variability — a therapeutic target? J Clin Pharmacy Ther 27: 85–92CrossRefGoogle Scholar
  28. 28.
    Li YL, Xia XH, Zheng H, et al (2006) Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits. Cardiovasc Res 71: 129–138PubMedCrossRefGoogle Scholar
  29. 29.
    Schmidt H, Hennen R, Keller A, et al (2005) ß-blocker treatment, heart rate variability, and survival of intensive care patients. Intensive Care Med 31(suppl l): A310 (abst)Google Scholar
  30. 30.
    Schmidt H, Hoyer D, Rauchhaus M, et al (2007) ACE-inhibitor therapy and survival among patients with multiorgan dysfunction syndrome of 24 to 96 years. Intensive Care Med 33(suppl): A722 (abst)Google Scholar

Copyright information

© Springer Science + Business Media Inc. 2008

Authors and Affiliations

  • H. Schmidt
    • 1
  • U. Müller-Werdan
    • 2
  • K. Werdan
    • 2
  1. 1.Neurological Intensive Care Unit Neurological Institute ColumbiaUniversity Medical CenterNew YorkUSA
  2. 2.Department of Medicine III Martin-LutherUniversity Halle-Wittenberg Klinikum KröllwitzHalle/SaaleGermany

Personalised recommendations