• Mary Anne M Morgan, Lauren M Frasier, Judith C Stewart, Cynthia M Mack, Michael S Gough, Brian T Graves, Michael J Apostolakos, Kathleen P Doolin, Denise C Darling, Mark W Frampton, and Anthony P Pietropaoli.
• Departments of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
• Crit. Care Med. 2010 Apr 1;38(4):1069-77.

ObjectiveNitric oxide deficiency may contribute to microvascular dysfunction in sepsis. Current physiologic paradigms contend that nitrite and/or S-nitrosohemoglobin mediate intravascular delivery of nitric oxide. These nitric oxide metabolites are purportedly consumed during hemoglobin deoxygenation, producing nitric oxide and coupling intravascular nitric oxide delivery with metabolic demand. Systemic nitrite and S-nitrosohemoglobin consumption can be assessed by comparing their concentrations in arterial vs. venous blood. We hypothesized that arterial vs. venous differences in nitrite and S-nitrosohemoglobin are diminished in sepsis and associated with mortality.DesignCase-control and prospective cohort study.SettingAdult intensive care units of an academic medical center.Patients And SubjectsEighty-seven critically ill septic patients and 52 control subjects.InterventionsNone.Measurements And Main ResultsNitrite and S-nitrosohemoglobin were measured using tri-iodide-based reductive chemiluminescence. In control subjects, arterial plasma, whole blood, and red blood cell nitrite levels were higher than the corresponding venous levels. In contrast, S-nitrosohemoglobin was higher in venous compared to arterial blood. In septic patients, arterial vs. venous red blood cell nitrite and S-nitrosohemoglobin differences were absent. Furthermore, the plasma nitrite arterial vs. venous difference was absent in nonsurvivors.ConclusionsIn health, nitrite levels are higher in arterial vs. venous blood (suggesting systemic nitrite consumption), whereas S-nitrosohemoglobin levels are higher in venous vs. arterial blood (suggesting systemic S-nitrosohemoglobin production). These arterial vs. venous differences are diminished in sepsis, and diminished arterial vs. venous plasma nitrite differences are associated with mortality. These data suggest pathologic disruption of systemic nitrite utilization in sepsis.

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