Compromised Glutamine - Glutamate Metabolism in a Pseudomonas Aeruginosa Induced Hyperdynamic Sepsis-Recovery Pig Model During an Anabolic Nutritional Intervention

Abstract

Abstract Objectives Optimal feeding in patients recovering from sepsis is critical to preserve muscle mass. In sepsis, glutamine (Gln) is considered a conditional essential amino acid and low plasma level of its precursor glutamate (Glu), is associated with higher mortality. An essential amino acid (EAA) mixture restores protein anabolism in the early recovery phase of acute septicemia in the pig. However, it is unclear whether interorgan Glu-Gln kinetics is also improved. Therefore, we measured the interorgan kinetics of Glu-Gln during a nutritional intervention with a balanced free amino acid (TAA) or EAA mixture in the early recovery phase of acute septicemia in the pig. Methods In catheterized pigs (±25 kg), acute septicemia was present for 6 hours (Pseudomonas aeruginosa: 3e,8 CFU/ml/h IV). At t = 6 h, recovery was started by a single dose gentamycin (5 mg/kg) and intra-gastric continuous feeding of a balanced free TAA or EAA mixture (pig muscle profile, 31 mg N/kg bw/h, 30% daily intake and dextrose 781 mg/kg bw/h) for 6 hours. We studied 3 groups (Healthy: H-TAA n = 12; Sepsis: S-TAA n = 13, S-EAA n = 12) over the last 3 hours of the intervention by measuring arterial and venous plasma concentrations (expressed as mean[low, high 95%CI]) and organ net balances of the portal drained viscera (PDV), liver, kidneys and hindquarter (HQ, muscle). Statistics: Net balances were tested with Wilcoxon Signed Rank Test. Group comparisons with ANOVA. Significance: P < 0.05. Results Plasma concentrations : Gln was increased only in S-EAA (23 [14,32]%) group. In contrast, Glu substantially decreased in S-TAA and S-EAA (32[25,40]; 35[28,43]%) groups. Net PDV balance:Increased Gln uptake in S-EAA (P = 0.0020), but zero balance of Glu. Net HQ balance: Gln release was higher in S-TAA and S-EAA(P = 0.0028;0.0143). However, no changes in Glu uptake. Net liver balance: Gln uptake was higher in S-TAA and S-EAA (P = 0.0155;0.0056). Reduced Glu release in S-TAA (P = 0.0250). Net kidney balance: Zero balance for Gln, Glu uptake decreased in S-TAA (P = 0.0403). Conclusions In the present model of an early recovery of septicemia, interorgan Glu-Gln metabolism and Glu plasma levels are not restored by anabolic intervention, suggesting additional supplementation needs. Funding Sources NIH R01GM084447 and S10RR027047.