Unbound MEDLINE

Hypothermia decreases cerebrospinal fluid asymmetric dimethylarginine levels in children with traumatic brain injury.

Abstract

OBJECTIVES
Pathological increases in asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, have been implicated in endothelial dysfunction and vascular diseases. Reduced nitric oxide early after traumatic brain injury may contribute to hypoperfusion. Currently, methods to quantify asymmetric dimethylarginine in the cerebrospinal fluid have not been fully explored. We aimed to develop and validate a method to determine asymmetric dimethylarginine in the cerebrospinal fluid of a pediatric traumatic brain injury population and to use this method to assess the effects of 1) traumatic brain injury and 2) therapeutic hypothermia on this mediator.
DESIGN, SETTING, AND PATIENTS
An ancillary study to a prospective, phase II randomized clinical trial of early hypothermia in a tertiary care pediatric intensive care unit for children with Traumatic brain injury admitted to Children's Hospital of Pittsburgh.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
A UPLC-MS/MS method was developed and validated to quantitate asymmetric dimethylarginine. A total of 56 samples collected over 3 days with injury onset were analyzed from the cerebrospinal fluid of consented therapeutic hypothermia (n = 9) and normothermia (n = 10) children. Children undergoing diagnostic lumbar puncture (n = 5) were enrolled as controls. Asymmetric dimethylarginine was present at a quantifiable level in all samples. Mean asymmetric dimethylarginine levels were significantly increased in normothermic Traumatic brain injury children compared with that in control (0.19 ± 0.08 µmol/L and 0.11 ± 0.02 µmol/L, respectively, p = 0.01), and hypothermic children had significantly reduced mean asymmetric dimethylarginine levels (0.11 ± 0.05 µmol/L) vs. normothermic (p = 0.03) measured on day 3. Patient demographics including age, gender, and nitric oxide levels (measured as nitrite and nitrate using liquid chromatography coupled with Griess reaction) did not significantly differ between normothermia and hypothermia groups. Also, nitric oxide levels did not correlate with asymmetric dimethylarginine concentrations.
CONCLUSIONS
Asymmetric dimethylarginine levels were significantly increased in the cerebrospinal fluid of traumatic brain injury children. Early hypothermia attenuated this increase. The implications of attenuated asymmetric dimethylarginine on nitric oxide synthases activity and regional cerebral blood flow after traumatic brain injury by therapeutic hypothermia deserve future study.

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  • Publisher Full Text
  • Authors

    Thampatty BP, Klamerus MM, Oberly PJ, Feldman KL, Bell MJ, Tyler-Kabara EC, Adelson PD, Clark RS, Kochanek PM, Poloyac SM

    Source

    Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 14:4 2013 May pg 403-12

    MeSH

    Adolescent
    Arginine
    Brain Injuries
    Case-Control Studies
    Cerebrospinal Fluid
    Child
    Child, Preschool
    Chromatography, Liquid
    Female
    Humans
    Hypothermia, Induced
    Infant
    Male
    Nitrates
    Nitrites
    Tandem Mass Spectrometry

    Pub Type(s)

    Clinical Trial, Phase II
    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    23439461