Reduced caloric intake during endotoxemia reduces arginine availability and metabolism

Abstract

Inadequate caloric intake increases the risk of sepsis-induced complications. Metabolic changes during sepsis indicate that the availability of the amino acid l-arginine decreases. Availability of arginine may further decrease during reduced caloric intake, which thereby limits the adaptive response of arginine-nitric oxide metabolism during sepsis. We tested the hypothesis that reduced caloric intake during endotoxemia, as an experimental model for sepsis, further reduces arginine availability. In a randomized trial, a 7-d reduced caloric intake feed regimen (RE; n = 9) was compared with a normal control feed regimen (CE; n = 9), before 24 h of endotoxemia, as a model for sepsis. Whole-body arginine-nitric oxide metabolism and protein metabolism were measured by using a stable-isotope infusion of [(15)N(2)]arginine, [(13)C-(2)H(2)]citrulline, [(2)H(5)]phenylalanine, and [(2)H(2)]tyrosine. Plasma pyruvate and lactate concentrations were determined by fully automated HPLC. Pre-endotoxin arginine appearance was significantly lower in the RE group than in the CE group (P = 0.002). During endotoxemia, arginine appearance increased in the CE animals but not in the RE animals (P = 0.04). In addition, nitric oxide production was significantly lower in the RE animals (P < 0.0001). Protein synthesis was significantly lower at the start of endotoxin infusion (P < 0.05) and remained lower during endotoxemia in the RE group than in the CE group (P < 0.001). The lactate:pyruvate ratio was not higher in the RE group than in the CE group before endotoxemia but increased significantly during endotoxemia in the RE group (P = 0.04). A well-nourished condition before prolonged endotoxemia results in a better ability to adapt to endotoxin-induced metabolic deterioration of arginine-nitric oxide metabolism than does reduced caloric intake before endotoxemia.