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Whole Body Protein Turnover and Net Protein Balance After Pediatric Thoracic Surgery: A Noninvasive Single‐Dose 15N Glycine Stable Isotope Protocol With End‐Product Enrichment
Authors:Brenna S. Fullerton MD  Eric A. Sparks MD  Faraz A. Khan MD  Jeremy G. Fisher MD  Rocco Anzaldi RPh  Michael R. Scoville CPhT  Yong‐Ming Yu MD  PhD  David A. Wagner PhD  Tom Jaksic MD  PhD  Nilesh M. Mehta MD
Affiliation:1. Department of Surgery, Boston Children’s Hospital and Harvard Medical School, Boston, Massachusetts, USA;2. Department of Pharmacy, Boston Children’s Hospital and Harvard Medical School, Boston, Massachusetts, USA;3. Department of Surgery, Shriner Burns Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA;4. Metabolic Solutions Inc, Nashua, New 5. Hampshire, USA;6. Division of Critical Care, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Abstract:Background : We used the 15N glycine urinary end‐product enrichment technique to quantify whole body protein turnover following thoracic surgery. Materials and Methods : A single dose of 15N glycine (2 mg/kg) was administered orally on postoperative day 1 to children (1–18 years) following thoracic surgery. 15N enrichment of ammonia and urea was measured in mixed urine after 12 and 24 hours, respectively, and protein synthesis, breakdown, and net balance determined. Nitrogen balance (dietary intake minus urinary excretion) was calculated. Urinary 3‐methylhistidine:creatinine ratio was measured as a marker of skeletal muscle protein breakdown. Results : We enrolled 19 subjects—median (interquartile range): age, 13.8 years (12.2–15.1); weight, 49.2 kg (38.4–60.8)—who underwent thoracotomy (n = 12) or thoracoscopic (n = 7) surgery. Protein synthesis and breakdown by 15N enrichment were 7.1 (5.5–9) and 7.1 (5.6–9) g·kg?1·d?1 with ammonia (12 hours) as the end product, and 5.8 (3.8–6.7) and 6.7 (4.5–7.6) with urea (24 hours), respectively. Net protein balance by the 15N glycine and urinary urea nitrogen methods were ?0.34 (?0.47, ?0.3) and ?0.48 (?0.65, ?0.28) g·kg?1·d?1, respectively (rs = 0.828, P < .001). Postoperative change in 3‐methylhistidine:creatinine ratio did not correlate significantly with protein breakdown or balance. Conclusion : The single‐dose oral administration of 15N glycine stable isotope with measurement of urinary end‐product enrichment is a feasible and noninvasive method to investigate whole body protein turnover in children. After major surgery, children manifest increased protein turnover and net negative balance due to increased protein breakdown.
Keywords:balance  breakdown  glycine  nutrition  proteins  stable isotope  synthesis  turnover
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