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Effect of l-NAME, an inhibitor of nitric oxide synthesis, on plasma levels of IL-6, IL-8, TNFα and nitrite/nitrate in human septic shock

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Abstract

Objectives: We tested the effects of NG-nitro-L-arginine methyl ester (l-NAME), an inhibitor of nitric oxide (NO) synthesis, on plasma levels of interleukin (IL) IL-6, IL-8, tumor necrosis factor-alpha (TNFα) and nitrite/nitrate (NO −2 /NO −3 ) in patients with severe septic shock.

Design: Prospective clinical study.

Setting: Surgical intensive care unit at a university hospital.

Patients: 11 consecutive patients with severe septic shock.

Interventions: Standard hemodynamic measurements were made and blood samples taken at intervals before, during, and after a 12-h infusion of l-NAME 1 mg · kg−1 ·h−1 for determination of plasma IL-6, IL-8, TNFα and NO −2 /NO −3 concentration.

Measurements and results: Patients with sepsis had increased plasma levels of IL-6, IL-8, TNFα, and NO −2 /NO −3 (p<0.05). Plasma levels of IL-6, IL-8, and NO −2 /NO −3 were negatively correlated with systemic vascular resistance (r=−0.62, r=−0.65, and r=−0.78, respectively, all p<0.05). Continuous infusion of l-NAME increased mean arterial pressure and systemic vascular resistance, with a concomitant reduction in cardiac output (all p<0.01). No significant changes were seen in levels of plasma IL-6, IL-8, and NO −2 /NO −3 during the 24-h observation period. Plasma levels of TNFα were significantly reduced during l-NAME infusion compared to baseline (p<0.05).

Conclusions: NO plays a role in the cardiovascular derangements of human septic shock. Inhibition of NO synthesis with l-NAME does not promote excessive cytokine release in patients with severe sepsis.

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Authors and Affiliations

  1. Department of Surgery and Intensive Care, University Hospital Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands

    J. A. M. Avontuur, T. C. Stam, A. M. M. Eggermont & H. A. Braining

  2. Department of Autoimmune Diseases, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, Amsterdam, The Netherlands

    M. Jongen-Lavrencic

  3. Department of Pharmacology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands

    J. G. C. van Amsterdam

Authors
  1. J. A. M. Avontuur
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  2. T. C. Stam
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  3. A. M. M. Eggermont
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  4. H. A. Braining
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  5. M. Jongen-Lavrencic
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  6. J. G. C. van Amsterdam
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Avontuur, J.A.M., Stam, T.C., Eggermont, A.M.M. et al. Effect of l-NAME, an inhibitor of nitric oxide synthesis, on plasma levels of IL-6, IL-8, TNFα and nitrite/nitrate in human septic shock. Intensive Care Med 24, 673–679 (1998). https://doi.org/10.1007/s001340050643

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  • DOI: https://doi.org/10.1007/s001340050643

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