Artery-to-vein differences in nitric oxide metabolites are diminished in sepsis

Departments of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Critical care medicine (Impact Factor: 6.31). 04/2010; 38(4):1069-77. DOI: 10.1097/CCM.0b013e3181d16a3e
Source: PubMed

ABSTRACT Nitric 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.
Case-control and prospective cohort study.
Adult intensive care units of an academic medical center.
Eighty-seven critically ill septic patients and 52 control subjects.
Nitrite 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.
In 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.

Download full-text


Available from: Brian Thomas Graves, Jan 16, 2014
22 Reads
  • Source
    • "This was a combined prospective cohort study and case-control study. The study design, clinical characteristics, and outcomes of many of the study subjects have been reported previously [29,30]. In brief, consecutive patients meeting diagnostic criteria for severe sepsis or septic shock [34] (subsequently collectively termed severe sepsis) in the medical or surgical intensive care unit (ICU) of the University of Rochester Medical Center were eligible. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Ultrasound measurements of brachial artery reactivity in response to stagnant ischemia provide estimates of microvascular function and conduit artery endothelial function. We hypothesized that brachial artery reactivity would independently predict severe sepsis and severe sepsis mortality. Methods This was a combined case-control and prospective cohort study. We measured brachial artery reactivity in 95 severe sepsis patients admitted to the medical and surgical intensive care units of an academic medical center and in 52 control subjects without acute illness. Measurements were compared in severe sepsis patients versus control subjects and in severe sepsis survivors versus nonsurvivors. Multivariable analyses were also conducted. Results Hyperemic velocity (centimeters per cardiac cycle) and flow-mediated dilation (percentage) were significantly lower in severe sepsis patients versus control subjects (hyperemic velocity: severe sepsis = 34 (25 to 48) versus controls = 63 (52 to 81), P < 0.001; flow-mediated dilation: severe sepsis = 2.65 (0.81 to 4.79) versus controls = 4.11 (3.06 to 6.78), P < 0.001; values expressed as median (interquartile range)). Hyperemic velocity, but not flow-mediated dilation, was significantly lower in hospital nonsurvivors versus survivors (hyperemic velocity: nonsurvivors = 25 (16 to 28) versus survivors = 39 (30 to 50), P < 0.001; flow-mediated dilation: nonsurvivors = 1.90 (0.68 to 3.41) versus survivors = 2.96 (0.91 to 4.86), P = 0.12). Lower hyperemic velocity was independently associated with hospital mortality in multivariable analysis (odds ratio = 1.11 (95% confidence interval = 1.04 to 1.19) per 1 cm/cardiac cycle decrease in hyperemic velocity; P = 0.003). Conclusions Brachial artery hyperemic blood velocity is a noninvasive index of microvascular function that independently predicts mortality in severe sepsis. In contrast, brachial artery flow-mediated dilation, reflecting conduit artery endothelial function, was not associated with mortality in our severe sepsis cohort. Brachial artery hyperemic velocity may be a useful measurement to identify patients who could benefit from novel therapies designed to reverse microvascular dysfunction in severe sepsis and to assess the physiologic efficacy of these treatments.
    Critical care (London, England) 03/2012; 16(2):R38. DOI:10.1186/cc11223 · 4.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Le choc septique se caractérise par une atteinte microcirculatoire avec un shunt, expliquant en partie les valeurs normales ou élevées de la saturation veineuse centrale en oxygène, souvent rencontrées dans ce contexte. Le monoxyde d’azote (NO) joue un rôle protecteur dans l’homéostasie microcirculatoire, alors même que, produit de façon importante lors du sepsis expérimental, il apparaît responsable d’une baisse de la pression artérielle et de la diminution de sensibilité aux vasoconstricteurs. L’inhibition des NO synthases diminue la survie des patients en choc septique. De plus en plus de données expérimentales et maintenant cliniques renforcent l’idée que les dérivés du NO pourraient être bénéfiques pour réduire l’atteinte microcirculatoire, voire même la mortalité. Une étude confirmant spécifiquement l’effet propre des dérivés nitrés sur la mortalité dans le sepsis sévère semble nécessaire, même si ces agents sont déjà utilisés dans certaines unités de réanimation.
    Réanimation 03/2012; 21(2). DOI:10.1007/s13546-012-0446-4
  • [Show abstract] [Hide abstract]
    ABSTRACT: Not Available
    Biomedical Engineering Conference, 1998. Proceedings of the 17th Southern; 03/1998
Show more