Effect of L-NAME, an inhibitor of nitric oxide synthesis, on plasma levels of IL-6, IL-8, TNF alpha and nitrite/nitrate in human septic shock.
OBJECTIVE
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 (TNFalpha) and nitrite/nitrate (NO2-/ NO3-) in patients with severe septic shock.


METHODS
Prospective clinical study.


METHODS
Surgical intensive care unit at a university hospital.


METHODS
11 consecutive patients with severe septic shock.


METHODS
Standard hemodynamic measurements were made and blood samples taken at intervals before, during, and after a 12-h infusion of L-NAME 1 mg x kg(-1) x h(-1) for determination of plasma IL-6, IL-8, TNFalpha and NO2-/NO3- concentration.


RESULTS
Patients with sepsis had increased plasma levels of IL-6, IL-8, TNFalpha and NO2-/NO3- (p < 0.05). Plasma levels of IL-6. IL-8, and NO2-/NO- 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-/NO3- during the 24-h observation period. Plasma levels of TNFalpha 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.
Department of Surgery, University Hospital Rotterdam, The Netherlands.
J A
JA
Avontuur
T C
TC
Stam
M
M
Jongen-Lavrencic
J G
JG
van Amsterdam
A M
AM
Eggermont
H A
HA
Bruining
D018806:APACHE; D016903:Drug Monitoring; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009566:Nitrates / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology*; D009573:Nitrites / Q000097:blood*; D011446:Prospective Studies; D012772:Shock, Septic / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D016209:Interleukin-8; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester