L-ARGININE - NITRIC-OXIDE PATHWAY IN ENDOTOXEMIA AND HUMAN SEPTIC SHOCK

Objective: To investigate the relationship between nitric oxide production, endotoxemia, and hemodynamic alterations in human septic shock, Design: Prospective study, Setting: A 32-bed intensive care unit in a university referral hospital, Patients: Two groups of septic patients with shock (n = 13) or without shock (n = 16) and an additional group of nonseptic patients as control group (n = 25), Measurements: Plasma nitrite and nitrate concentrations were measured as an index of nitric oxide generation, Nitrite and nitrate concentrations were correlated with plasma endotoxin and hemodynamic variables. Main Results: Increased plasma nitrite and nitrate concentrations were found in patients with septic shock (p < .01), Nitrite and nitrate correlated directly with endotoxin concentrations r(2) = .21, p < .05) and cardiac output (r(2) = .49, p < .05), and inversely with systolic blood pressure (r(2) = .24, p < .01). Conclusions: This study demonstrated the activation of the L-arginine:nitric oxide pathway in human endotoxemic septic shock, suggesting that nitric oxide may be an important mediator of the hemodynamic disturbances in this pathophysiologic situation.