The objectives are to test the hypothesis that the acute response to trauma can be separated into two components. One component involves the shifting of body fuel metabolism from glucose to lipid. The other component is a hypermetabolic response which includes increased lymphocytic activity, acute phase protein synthesis and various wound repair related processes, the sum of which result in an increased whole body protein synthesis rate (PSR). If the adaptation to lipids is effected pre-trauma only the hypermetabolic response should occur. Preliminary data from rats support the hypothesis. Pre-adaption to lipid results in less N excretion and a higher whole body protein synthesis rates post- trauma than in rats not pre-adapted to lipid. The hypothesis will be tested in rats and man. I Rats. Rats (220-240g) will be fed IG or IV one of two isonitrogenous (1.5 gN/kg/d), isocaloric (240 kcal/kg/d) diets differing in the glucose:lipid ratio. Diet G (glucose) 90:10, diet L (lipid) 20:80. We will: 1, Determine whether the reason for the whole body PSR being higher post-trauma in lipid-adapted rats is that (i) muscle protein synthesis (measured by pool flooding with 14C leucine and immunoprecipitation) are higher in the lipid- adapted group. 2, If differences are found determine whether they are related to glutamine production (by 5-13C-L glutamine). 3, Determine whether the mechanism for shift in fuel utilization following trauma is similar to that in early starvation. II Man. Patients (20) with inflammatory bowel disease on TPN requiring an exploratory laparotomy will be randomized into two groups, G and L. They will be given TPN with either glucose (group G) or 50% lipid and 50% glucose (group L) for 5 days before and 5 days after surgery. 3 days pre and 1-2 days post-op we will measure: PSR (15N glycine), glucose production (6,6 D glucose), Urea production (18O urea) and glutamine production (5-13C L- Glutamine). Daily N balance and 3 Methyl histidine (3-MeH) excretion will be measure. If the hypothesis is correct, the post- trauma N loss, 3-MeH excretion, glucose production, glutamine production should be less and the PSR greater for the L as compared to the G group.
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