Release of endothelin in relation to tumor necrosis factor-alpha in porcine Pseudomonas aeruginosa-induced septic shock

Septic shock is characterized by surges of tumor necrosis factor-alpha (TNF-alpha) along with myocardial dysfunction and systemic hypotension. TNF-alpha promotes the release of immunoreactive endothelin (ET). Because TNF-alpha is elevated in septic shock, we hypothesized that elevated levels of endo...

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Bibliographic Details
Published in:	Shock (Augusta, Ga.) Vol. 1; no. 5; p. 343
Main Authors:	Han, J J, Windsor, A, Drenning, D H, Leeper-Woodford, S, Mullen, P G, Bechard, D E, Sugerman, H J, Fowler, 3rd, A A
Format:	Journal Article
Language:	English
Published:	United States 01-05-1994
Subjects:	Animals Antibodies, Monoclonal - immunology Disease Models, Animal Endothelins - agonists Endothelins - blood Hemodynamics - drug effects Immunization Infusions, Intravenous Pseudomonas aeruginosa Pseudomonas Infections - metabolism Shock, Septic - metabolism Shock, Septic - microbiology Swine Tumor Necrosis Factor-alpha - immunology Tumor Necrosis Factor-alpha - metabolism
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Summary:	Septic shock is characterized by surges of tumor necrosis factor-alpha (TNF-alpha) along with myocardial dysfunction and systemic hypotension. TNF-alpha promotes the release of immunoreactive endothelin (ET). Because TNF-alpha is elevated in septic shock, we hypothesized that elevated levels of endothelin can contribute to cardiac dysfunction and hypotension. We infused live Pseudomonas aeruginosa into anesthetized, hemodynamically monitored young swine and measured ET and TNF-alpha. Septic swine developed systemic arterial hypotension and had significantly elevated TNF-alpha (4.15 +/- .41 U/ml at 1 h versus .40 +/- .13 U/ml at time zero) compared to control animals. ET levels were significantly elevated at 4 h (52.38 +/- 12.88 pg/ml vs. 10.45 +/- 1.82 pg/ml at time zero) and correlated negatively with the decline in cardiac output. We then passively immunized swine using anti TNF-alpha prior to the induction of sepsis to examine if TNF played a central role in the release ET. The anti TNF-alpha effectively removed circulating TNF-alpha bioactivity in septic animals. Anti-TNF-alpha-treated animals did not develop significant systemic arterial hypotension and had significant attenuation in endothelin (19.01 +/- 4.18 pg/ml at 4 h compared to 52.38 +/- 12.88 pg/ml in septic animals at 4 h) which correlated with preservation of cardiac output. TNF-alpha may cause cardiac dysfunction in sepsis syndrome through increased release of ET.
ISSN:	1073-2322
DOI:	10.1097/00024382-199405000-00004