Muscle Protein Synthesis after Protein Administration in Critical Illness

Abstract

<b>Rationale:</b> Dietary protein may attenuate the muscle atrophy experienced by patients in the ICU, yet protein handling is poorly understood. <b>Objectives:</b> To quantify protein digestion and amino acid absorption and fasting and postprandial myofibrillar protein synthesis during critical illness. <b>Methods:</b> 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 <i>t</i> test. <b>Measurements and Main Results:</b> 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; <i>P</i> = 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%; <i>P</i> = 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 <i>P</i> = 0.046; <i>P</i>-interaction = 0.584) with lower rates in ICU patients than in healthy control subjects (main group effect <i>P</i> = 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; <i>P</i> = 0.007). <b>Conclusions:</b> 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.