title: Arginine and nitric oxide metabolism in critically ill septic pediatric patients.
abstract: OBJECTIVE
  To investigate whole body, arginine metabolism and nitric oxide synthesis rates in septic, critically ill pediatric patients.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Pediatric intensive care unit at a general hospital.
  
  
  METHODS
  Ten consecutive septic patients age 6-16 yrs.
  
  
  METHODS
  Septic patients received an 8-hr primed, constant intravenous tracer infusion of L-[guanidino-15N2]arginine, L-[1-13C]leucine, and [13C]urea. A 24-hr urine collection was obtained for determination of [15N]nitrate enrichment (15NO3(-)) and urinary nitrogen. The next day they received an infusion of L-[5-13C]arginine and L-[5-13C-ureido, 5,5, 2H2]citrulline. Blood samples were obtained for determination of plasma isotopic enrichment of the tracers given and of derived [15N]citrulline (nitric oxide synthesis), L-[13C-guanidino 5,5, 2H2]arginine (M+3 arg) (arginine synthesis), and [15N]urea (urea formation). Data are compared with historic controls from studies in healthy young adults.
  
  
  RESULTS
  Plasma arginine fluxes were 67 +/- 21 and 72 +/- 17 micromol x kg(-1) x hr(-1), respectively, for the [15N2 guanidino] and the [13C] arginine labels, which were not different from reported adult values. The rates of arginine oxidation were 22.9 +/- 10.8 micromol x kg(-1) x hr(-1) and were higher than arginine synthesis rates of 9.6 +/- 4.2 micromol x kg(-1) x hr(-1) (p <.01); therefore, these patients were in a negative arginine balance. The rates of nitric oxide synthesis as estimated by the [15N]citrulline method were 1.58 +/- 0.69 micromol x kg(-1) x hr(-1) for septic patients and higher (p <.05) than values of 0.96 +/- 0.1 micromol x kg(-1) x hr(-1) in healthy adults. Septic patients were in a negative protein (leucine) balance of about -1.00 +/- 0.40 g x kg(-1) x day(-1).
  
  
  CONCLUSIONS
  Homeostasis of plasma arginine in septic patients was impaired compared with reported adult values. The rates of arginine oxidation were increased whereas net arginine synthesis was unchanged, leading to a negative arginine balance. The rates of nitric oxide synthesis and the fraction of plasma arginine used for nitric oxide and urea formation were increased. These findings suggest that under condition of sepsis, arginine becomes essential in critically ill children.
authors.affiliation: Pediatric Service, Massachusetts General Hospital, Boston, USA.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Argaman
authors.forename: Vernon R
authors.initials: VR
authors.lastname: Young
authors.forename: Natan
authors.initials: N
authors.lastname: Noviski
authors.forename: Luis
authors.initials: L
authors.lastname: Castillo-Rosas
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Lu
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.forename: Mehrengise
authors.initials: M
authors.lastname: Cooper
authors.forename: Caroline
authors.initials: C
authors.lastname: Davison
authors.forename: John F
authors.initials: JF
authors.lastname: Tharakan
authors.forename: Alfred
authors.initials: A
authors.lastname: Ajami
authors.forename: Leticia
authors.initials: L
authors.lastname: Castillo
mesh_terms: D000293:Adolescent; D001120:Arginine / Q000378:metabolism*; D002648:Child; D016638:Critical Illness; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011446:Prospective Studies; D018805:Sepsis / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D001120:Arginine