Muscle Protein Synthesis Following Protein Administration in Critical Illness

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 506 17 yr; body mass index, 276 5 kg m22 ) and 10 healthy control subjects (6 male; 546 23 yr; body mass index, 276 4 kg m22 ) received a primed intravenous L-[ring-2 H5]-phenylalanine, L-[3,5-2 H2]-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 mean6 SD, analyzed with two-way repeated measures ANOVA and independent samplest test. Measurements and Main Results: Fasting myofibrillar protein synthesis rates did not differ between ICU patients and healthy control subjects (0.0236 0.013% h21 vs. 0.0346 0.016% h21 ; P= 0.077). After protein administration, plasma amino acid availability did not differ between groups (ICU patients, 54.26 9.1%, vs. healthy control subjects, 61.86 13.1%; P= 0.12), and myofibrillar protein synthesis rates increased in both groups (0.0286 0.010% h21 vs. 0.0436 0.018% h21 ; 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 (0.0076 0.007 mol percent excess vs. 0.0176 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.