Muscle Protein Synthesis after Protein Administration in Critical Illness

Abstract

Abstract Rationale Dietary protein may attenuate the muscle atrophy experienced by patients in the ICU, yet protein handling is poorly understood. Objectives To quantify protein digestion and amino acid absorption and fasting and postprandial myofibrillar protein synthesis during critical illness. Methods Fifteen mechanically ventilated adults (12 male; aged 50 ± 17 yr; body mass index, 27 ± 5 kg⋅m−2) and 10 healthy control subjects (6 male; 54 ± 23 yr; body mass index, 27 ± 4 kg⋅m−2) received a primed intravenous L-[ring-2H5]-phenylalanine, L-[3,5-2H2]-tyrosine, and L-[1-13C]-leucine infusion over 9.5 hours and a duodenal bolus of intrinsically labeled (L-[1-13C]-phenylalanine and L-[1-13C]-leucine) intact milk protein (20 g protein) over 60 minutes. Arterial blood and muscle samples were taken at baseline (fasting) and for 6 hours following duodenal protein administration. Data are mean ± SD, analyzed with two-way repeated measures ANOVA and independent samples t test. Measurements and Main Results Fasting myofibrillar protein synthesis rates did not differ between ICU patients and healthy control subjects (0.023 ± 0.013% h−1 vs. 0.034 ± 0.016% h−1; P = 0.077). After protein administration, plasma amino acid availability did not differ between groups (ICU patients, 54.2 ± 9.1%, vs. healthy control subjects, 61.8 ± 13.1%; P = 0.12), and myofibrillar protein synthesis rates increased in both groups (0.028 ± 0.010% h−1 vs. 0.043 ± 0.018% h−1; main time effect P = 0.046; P-interaction = 0.584) with lower rates in ICU patients than in healthy control subjects (main group effect P = 0.001). Incorporation of protein-derived phenylalanine into myofibrillar protein was ∼60% lower in ICU patients (0.007 ± 0.007 mol percent excess vs. 0.017 ± 0.009 mol percent excess; P = 0.007). Conclusions The capacity for critically ill patients to use ingested protein for muscle protein synthesis is markedly blunted despite relatively normal protein digestion and amino acid absorption.