Metabolism of L-arginine and the no pathway in septic children

To determine the in vivo status and regulatory mechanisms of arginine and related metabolic pathways in septic children, we conducted an 8h primed constant intravenous infusion of L-[¹³C] leu and L-[guanidino ¹⁵N₂, 5,5,²H₂] arg in 10 septic children (6 to 16y; 20-60kg). Four patients also received a second infusion of L-[¹³C] arg and L-[¹³C ureido 5,5,²H₂] cit the next day. Frequent blood, breath, urine samples and indirect calorimetry were obtained. Isotopic enrichments were measured by GC-MS and IR-MS. Six healthy young adults (18-21y; 60-80kg); receiving adequate protein and energy intake for a week served as controls. Group De novo Arg Synthesis Arg Ox NO Synthesis Arg to Cit Plasma Arg to NO₃-Septic 9.6±31 16.9±3*1.6±0.9*11.7±5*Healthy 9.2±1.4 7.6±0.4 0.96±0.1 1.7±4 1 All Values are Mean ± Sem; μmol.kg.h;*p<0.05 Homeostasis of arg metabolism in septic patients is impaired. Arg oxidation is greater than synthesis, resulting in a negative arg balance. NO synthesis was increased and appeared to reflect severity of disease. Plasma arg for NO synthesis is utilized to a greater extent in septic patients.