Reduced caloric intake during endotoxemia reduces arginine availability and metabolism.
BACKGROUND
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.


OBJECTIVE
We tested the hypothesis that reduced caloric intake during endotoxemia, as an experimental model for sepsis, further reduces arginine availability.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands. m.poeze@ah.unimaas.nl
Martijn
M
Poeze
Maaike J
MJ
Bruins
Yvette C
YC
Luiking
Nicolaas E
NE
Deutz
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications / Q000378:metabolism*; D004731:Endotoxins; D002149:Energy Intake; D004926:Escherichia coli; D019344:Lactic Acid / Q000378:metabolism; D008070:Lipopolysaccharides; D009569:Nitric Oxide / Q000096:biosynthesis*; D011502:Protein-Energy Malnutrition / Q000150:complications / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D011897:Random Allocation; D013552:Swine
D004731:Endotoxins; D008070:Lipopolysaccharides; D011506:Proteins; D009569:Nitric Oxide; D019344:Lactic Acid; D019289:Pyruvic Acid; D001120:Arginine