Use of the neonatal piglet as a model for protein and amino acid metabolism in premature infants: 1. Use of body carbohydrate, lipid and protein during total and partial starvation. 2. Negative impact of dexamethasone treatment on growth, protein synthes

The neonatal piglet was used as a model for the premature infant to study protein and amino acid metabolism in response to starvation and dexamethasone treatment. Estimates of endogenous fuel use were obtained in piglets starved or given nonprotein fuel intravenously from 12–72h after birth. Provision of fuel decreased body dry matter loss and endogenous fuel use by 40%. However, body protein was not preferentially spared, as the contribution of protein, lipid and glycogen to endogenous fuel loss was approximately 39, 24 and 37%, respectively, for both starved and IV fuel pigs. The piglet was then used to study the protein catabolic effects of dexamethasone (dex), a drug used to alleviate severe lung disease in premature infants. Two experiments confirmed that pigs and preterm infants respond similarly to dex. Rates of weight and linear gain decreased, while BUN and urinary N excretion increased, when dex (0.25–1 mg/(kgd)) was given for 4–7d. In the final experiment, rates of valine oxidation and protein synthesis during (2d or 4d) and after (2d or 4d) dex treatment (0, 0.25, or 1 mg/(kgd)) were determined. A single intravenous injection of 1-14C valine was used to quantify valine flux and oxidation, and a flooding dose of 3H-valine served to measure protein synthesis. Dex treatment decreased the rate of weight gain 15–28%, increased valine oxidation 35–65%, decreased net protein gain 10–30%, and reduced the fractional rate of protein synthesis in lung, heart and skeletal muscle 13–23% after 4d of treatment. There was no evidence that the effects of dex on protein metabolism persisted beyond the treatment period. In general, treatment with 0.25 mg/(kgd) resulted in ∼50% of the negative growth and metabolic effects of 1 mg/(kgd). Changes in the rate of weight gain and valine oxidation appeared to be established after 2d of treatment but were not necessarily different from controls. Based on elevated whole-body amino acid oxidation and decreased fractional rates of protein synthesis in muscle, we conclude that the growth suppression seen with dex treatment is primarily due to decreased protein synthesis, rather than accelerated protein breakdown.