Whole Body Protein Turnover and Net Protein Balance After Pediatric Thoracic Surgery: A Noninvasive Single-Dose 15 N Glycine Stable Isotope Protocol With End-Product Enrichment

Abstract

Background: We used the ¹⁵ N glycine urinary end-product enrichment technique to quantify whole body protein turnover following thoracic surgery.

Materials and methods: A single dose of ¹⁵ N glycine (2 mg/kg) was administered orally on postoperative day 1 to children (1-18 years) following thoracic surgery. ¹⁵ N 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 ¹⁵ N 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 ¹⁵ N 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 (r_s = 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 ¹⁵ N 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.