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Role of Cytokines in Septic Cardiomyopathy

  • Chapter
Angiotensin II Receptor Blockade Physiological and Clinical Implications

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 2))

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Summary

The interrelations of cytokine and nitric oxide (NO) metabolism with heart function have been best documented for the heart in sepsis. The existence of human septic myocardial depression in intensive care patients was only unequivocally proved in the 1980s by the group of Parrillo, utilizing a nuclear imaging technique. Septic cardiomyopathy is frequently masked by a seemingly normal cardiac output. However, relative to the lowered systemic vascular resistance in sepsis, resulting in a reduced afterload, cardiac outputs and ventricular ejection fractions of septic patients are often not adequately enhanced. Septic cardiomyopathy involves both the right and the left ventricle; global as well as regional contractile disturbances occur and systolic pump as well as diastolic relaxation failure. Septic cardiomyopathy is potentially reversible. In response to volume substitution, the hearts can be considerably enlarged. The disease is not primarily hypoxic in nature, as coronary sinus blood flow is high and as coronary vessels are dilated. Difficult situations may arise, when septic cardiomyopathy develops in patients with pre-existing coronary heart disease. The severity of myocardial depression correlates with a poor prognosis, heart failure accounting for about 10% of fatalities from sepsis and septic shock. Septic cardiomyopathy is prevalent in Gram-positive, Gram-negative, fungal and viral sepsis, and left ventricular stroke work indices are compromised to a similar degree independent of the causative germ, pointing at the relevance of the final mediator pathways as opposed to the specific virulence factors.

The etiology of the disease is multifactorial. Several candidates with potential pathogenetic impact can be addressed: bacterial toxins, cytokines and mediators including nitric oxide, cardiodepressant factors, oxygen reactive species, catecholamines. Using cultures of neonatal rat cardiomyocytes, several “negative inotropic cascades” were identified. Experimentally supported concepts include the endotoxin-induced release of cytokines with cardiodepressant action, primarily tumor necrosis factor a (TNFα) and interleukin-1; induction of inducible nitric oxide synthase (iNOS) in cardiomyocytes was shown for endotoxin and interleukin-1; TNFα has pleiotropic effects including a concentration-dependent iNOS-induction, a decreased synthesis of precursors of the phosphoinositide pathway, interference with the β-adrenoceptor/G-protein/adenylyl cyclase-pathway and a decrease in calcium transient; a cardiodepressant factor (CDF) isolated from blood of patients in septic/cardiogenic shock blocks calcium current into cardiomyocytes.

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Authors and Affiliations

  1. Chair of Cardiac Intensive Care at the Department of Medicine III, Klinikum Kröllwitz, University of Halle-Wittenberg, Halle, Germany

    Ursula Müller-Werdan, Harald Loppnow, Susann Koch, Fritjof Schlegel & Karl Werdan

  2. Institute of Pathophysiology, University of Halle-Wittenberg, Halle, Germany

    Heike Schumann, Dorothea Darmer & JüRgen Holtz

  3. Department of Medicine I and Klinikum Großhadern, University of Munich, München, Germany

    Ralph Fuchs & Christopher Reithmann

  4. Department of Medicine II, Klinikum Großhadem, University of Munich, München, Germany

    Chang He

  5. Max-Planck-Institute of Infection Biology, Berlin, Germany

    Ursula Zimny-Arndt & Peter Jungblut

  6. Department of Surgery, Technical University of Munich, München, Germany

    Josef Stadler

Authors
  1. Ursula Müller-Werdan
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  2. Heike Schumann
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  3. Ralph Fuchs
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  7. Ursula Zimny-Arndt
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  8. Fritjof Schlegel
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  9. Chang He
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  10. Dorothea Darmer
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  11. Peter Jungblut
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  12. Josef Stadler
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  13. JüRgen Holtz
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  14. Karl Werdan
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Editor information

Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla Ph.D., M.D. (Hon.) (Distinguished Professor and Director MRC Group in Experimental Cardiology), Peter Zahradka Ph.D. (Associate Professor), Ian M. C. Dixon Ph.D. (Assistant Professor) & Robert E. Beamish M.D. (Professor Emeritus) (Distinguished Professor and Director MRC Group in Experimental Cardiology),  (Associate Professor),  (Assistant Professor) &  (Professor Emeritus)

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© 1998 Springer Science+Business Media New York

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Müller-Werdan, U. et al. (1998). Role of Cytokines in Septic Cardiomyopathy. In: Dhalla, N.S., Zahradka, P., Dixon, I.M.C., Beamish, R.E. (eds) Angiotensin II Receptor Blockade Physiological and Clinical Implications. Progress in Experimental Cardiology, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5743-2_16

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  • DOI: https://doi.org/10.1007/978-1-4615-5743-2_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7631-6

  • Online ISBN: 978-1-4615-5743-2

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