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Articles in PresS, published online ahead of print July 16, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00220.2002
Submitted on May 20, 2002
Accepted on July 15, 2002
1 Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
* To whom correspondence should be addressed. E-mail: tdavis{at}bcm.tmc.edu.
Protein synthesis in skeletal muscle is reduced by as much as 50% as early as 4 h after a septic challenge in adults. However, the effect of sepsis on muscle protein synthesis has not been determined in neonates, a highly anabolic population whose muscle protein synthesis rates are elevated and uniquely sensitive to insulin and amino acid stimulation. Neonatal piglets (n=10/group) were infused for 8 h with endotoxin [lipopolysaccharide (LPS), 0 and 10 µg/(kg{chemp}hr)]. Plasma amino acid and glucose concentrations were kept at the fed level by infusion of dextrose and a balanced amino acid mixture. Fractional protein synthesis rates were determined using a flooding dose of 3H-phenylalanine. LPS infusion produced a septic-like state as indicated by an early and sustained elevation in body temperature, heart rate, and plasma TNF-
, IL-1, cortisol, and lactate concentrations. Plasma levels of insulin increased while glucose and amino acids decreased, suggesting the absence of insulin resistance. LPS significantly reduced protein synthesis in longissimus dorsi muscle by only 11% and gastrocnemius by only 15%, but had no significant effect in masseter and cardiac muscles. LPS increased protein synthesis in the liver (22%), spleen (28%), kidney (53%), jejunum (19%), diaphragm (21%), lung (50%), and skin (13%), but not in the stomach, pancreas, or brain. These findings suggest that when substrate supply is maintained, skeletal muscle protein synthesis in neonates is relatively resistant to the catabolic effects of sepsis when compared to adults.
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