PLASMA ARGININE AND LEUCINE KINETICS AND UREA PRODUCTION-RATES IN BURN PATIENTS

We measured plasma arginine and leucine kinetics and rates of urea pro duction (appearance) in 12 severely burned patients (mean body surface burn area, 48%) during a basal state (low-dose intravenous glucose) a nd while receiving routine, total parenteral nutrition ([TPN] fed stat e) including an L-amino acid mixture, supplying a generous level of ni trogen (mean, 0.36 g N . kg(-1) . d(-1)). The two nutritional states w ere studied in random order using a primed 4-hour constant intravenous tracer infusion protocol. Stable-nuclide-labeled tracers were L-[guan idino-C-13]arginine, L-[1-C-13]leucine, [O-18]urea, and (NaHCO3)-C-13 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, alph a ketoisocaproate ([KIC] for leucine), and urea in plasma and (CO2)-C- 13 in breath. Results are compared with data obtained in these laborat ories in healthy adults. Leucine kinetics (flux and disappearance into protein synthesis) indicated the expected higher turnover in burn pat ients than in healthy controls. Mean leucine oxidation rates are also higher and compared well with values predicted from urea production ra tes, provided that urea nitrogen recycling via intestinal hydrolysis i s taken into account, The plasma urea flux was also higher than for no rmal subjects. Arginine fluxes as measured in the systemic whole body, via the plasma pool, were correspondingly higher in burned patients t han in healthy controls and were in good agreement with values predict ed from leucine-KIC kinetics. However, systemic whole-body arginine fl ux measured via the plasma pool was only 20% of the arginine flux esti mated from the urea flux plus the rate of protein synthesis. This find ing is strong evidence that there is a significant synthesis of argini ne (probably via recycling of ornithine) occurring in a sequestered po ol (presumably in the hepatocyte) that is not in close communication w ith the plasma pool. Further, these data for plasma arginine flux sugg est that the net rate of arginine degradation is increased in burn tra uma, while there also appears to be a continued low and possibly uncha nged net rate of de novo arginine synthesis contributing arginine to t he plasma pool. This interpretation leads to the conclusion that there are at least two significant metabolic pools of arginine, one highly sequestered related specifically to urea synthesis and the other a sys temic pool in equilibrium with the plasma, Because the hepatic urea ar ginine cycle does not contribute substantially to making arginine avai lable for protein synthesis, we propose from these findings that argin ine is a conditionally essential (indispensable) amino acid in the nut rition of severely burned patients and that an exogenous arginine sour ce is needed to maintain arginine balance. Copyright (C) 1995 by W.B. Saunders Company