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Combined Oxandrolone and Propranolol Therapy Attenuate Protein Breakdown in Severely Burned Pediatric Patients
Author(s) -
Chao Tony,
Herndon David N,
Porter Craig,
Malagaris Ioannis,
Abdelrahman Doaa Reda,
Suman Oscar E,
Sidossis Labros S
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1245.34
Subject(s) - oxandrolone , hypermetabolism , medicine , protein catabolism , skeletal muscle , propranolol , placebo , scalding , endocrinology , anesthesia , gastroenterology , chemistry , pathology , biochemistry , hormone , growth hormone , alternative medicine , food science , amino acid
Severe burn result in prolonged hypermetabolism and increased skeletal muscle catabolism. Propranolol has been shown to blunt the hypermetabolic stress response to burns while oxandrolone was shown to improve muscle protein synthesis efficiency. However, the effect of combined oxandrolone and propranolol therapy on skeletal muscle fractional synthesis (FSR) and breakdown (FBR) rates are not known. The objective of this study is to determine the effects of oxandrolone and propranolol (oxprop) treatment on skeletal muscle protein turnover in severely burned pediatric patients. In this placebo controlled clinical trial, we hypothesize that oxprop will improve skeletal muscle protein turnover in pediatric burn patients. Method We studied 24 pediatric patients with severe burns (≥ 30% total body surface area; TBSA) during their inpatient hospitalization. Patients were randomized to placebo (14 control) or oxprop (10). Protein kinetics were determined with bolus injections of 13 C 6 and 15 N phenylalanine at 2 and 4 weeks post‐injury. Skeletal muscle biopsies were obtained from the m. vastus lateralis . Plasma and muscle intracellular and bound protein pool enrichments were determined by gas chromatography‐mass spectrometry (GCMS). A Mann‐Whitney test was performed between groups. Significance was determined at p<0.05. Results Patients were similar in age (8 ± 6yr) and TBSA (53 ± 17% vs 48 ± 8%) between the control and oxprop groups. Muscle FSR was not different between control and oxprop at 2 weeks (0.13 ± 0.04%/h vs 0.08 ± 0.01%/h, p=0.73) or 4 weeks (0.16 ± 0.03%/h vs 0.13 ± 0.02%/h, p=0.92). FBR was not different between control and oxprop at 2 weeks (0.27 ± 0.05%/h vs 0.20 ± 0.02%/h, p=0.27). At 4 weeks, FBR in the oxprop group was significantly less than control (0.14 ± 0.02%/h vs 0.28 ± 0.04%/h, p<0.05). Protein net balance was not different between control and oxprop at 2 weeks (−0.14 ± 0.03%/h vs −0.12 ± 0.03%/h, p=0.33). At 4 weeks, net balance was improved in oxprop versus control (−0.01 ± 0.02%/h vs −0.12 ± 0.04%/h, p<0.05). Conclusion Combined oxandrolone and propranolol therapy significantly improves skeletal muscle protein turnover in pediatric burn patients after 4 weeks of treatment. The improvement in skeletal muscle protein net balance with oxprop treatment is achieved by blunting protein breakdown. Treatment with oxandrolone and propranolol for 4 weeks can blunt the catabolic effect seen in severe burn injury. Support or Funding Information NIH (P50 GM060338, R01 GM056687, R01 HD049471 and T32 GM008256), NIDILRR (90DP00430100) and Shriners Hospitals for Children (84080, 84090, 71006, 71008 and 71009) grants.