Muscle Protein Synthesis after Protein Administration in Critical Illness

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-H-2(5)]-phenylalanine, L-[3,5-H-2(2)]-tyrosine, and L-[1-C-13]-leucine infusion over 9.5 hours and a duodenal bolus of intrinsically labeled (L-[1-C-13]-phenylalanine and L-[1-C-13]-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 similar to 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.