title: Isotopic study of L-Arginine kinetics in the lung during pseudomonas sepsis in an ovine model.
abstract: The objective of the study is to investigate how L-Arginine pulmonary metabolism is altered in response Pseudomonas aeruginosa (P. aeruginosa) induced septic conditions using an ovine model.
  
  
  METHODS
  Seven female sheep were infused with a primed-constant infusion of L-[(15)N2-guanidino, 5, 5, (2)H2] L-Arginine for 28 hs. After the initial 4 hs of the L-Arginine infusion, a continuous infusion of live Pseudomonas aeruginosa bacteria started for 24 hs. A NO synthase (NOS) inhibitor, N(G)-Methyl-L-arginine (L-NMA), infusion was added during the last 4 hs of the bacterial infusion. Blood samples were taken at specific time points for isotopic enrichment during control, septic and NOS blocking phases of the study.
  
  
  RESULTS
  We observed that the level of total delivery of L-Arginine to the lungs was significantly decreased in septic phase after 24 hours of pseudomonas infusion. In contrast, the fractional uptake and metabolism of L-Arginine by the lungs was doubled during septic phase relative to the control phase (MARG-basal = 100% vs. MARG-septic = 220 ± 56%, P < 0.05). NO production in the lungs was also significantly increased. Infusion of L-NMA markedly blunted this elevated NO production and attenuated the total arginine metabolized in the septic lungs (Mnitrate-septic = 43.6 ± 5.7 vs. Mnitrate-septic + L-NMA = 13.4 ± 5.1 umol/kg/min; p < 0.05). We demonstrated sepsis induced by P. aeruginosa infusion caused an increase in the fractional uptake and metabolic rate of arginine in the lungs. Furthermore, our data suggests that arginine was mainly consumed via arginine - NO pathway, which might be responsible for this enhanced arginine metabolic activity in the septic lungs.
authors.affiliation: Shriners Hospital for Children and Massachusetts General Hospital Boston 02114, USA.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Xu
authors.forename: Davin
authors.initials: D
authors.lastname: Watson
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Yu
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
authors.forename: Stefani
authors.initials: S
authors.lastname: Fischer
authors.forename: Joan
authors.initials: J
authors.lastname: Nichols
authors.forename: Donald
authors.initials: D
authors.lastname: Deyo
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Traber
authors.forename: Joaquin
authors.initials: J
authors.lastname: Cortiella
keywords: Arginine; Pseudomonas aeruginosa; fractional uptake; isotopic study; nitric oxide; nitric oxide synthase; sepsis