Muscle protein synthesis : Effects of metabolic stress and feeding

Abstract: Surgical trauma and critical illness are pathophysiological conditions where the metabolic stress leads to an imbalance between protein synthesis and protein breakdown, resulting in a net loss of body proteins. A major part of the protein losses comes from skeletal muscle. Muscle depletion is associated with a high morbidity and mortality. To understand the changes that occur during critical illness and following trauma it is therefore necessary to study protein metabolism on the tissue level. The aim of this thesis work was to investigate the impact of metabolic stress and feeding on muscle protein synthesis. Healthy patients undergoing elective surgery and critically ill patients in the intensive care unit were investigated by the flood technique, employing L-[2H5] phenylalanine, for quantification of muscle protein synthesis rate. The effect of continuous and ongoing total parenteral nutrition was investigated in healthy patients scheduled for elective abdominal surgery of medium size. Muscle protein synthesis rate was determined before surgery and 24 hours after surgery with continuous and ongoing total parenteral nutrition. Conventional TPN could not prevent the decrease in muscle protein synthesis rate as compared to a control group receiving saline. Whereas conventional total parenteral nutrition is not effective in the immediate postoperative period it is shown that provision of glutamine can attenuate the decrease in muscle protein synthesis. However, glutamine is only marginally effective on muscle protein synthesis in ICU patients. To evaluate if a large enough dose of intravenous glutamine supplementation would influence muscle protein synthesis, ICU patients were randomized to receive 0, 20, 40 or 60 g of glutamine per kg body weight and day for a five-day study period. The main result was that plasma glutamine concentrations were normalized in all glutamine treated groups. No increase was seen in muscle glutamine concentration and therefore glutamine had no effect on muscle protein synthesis rate. The effect of difference size of trauma on muscle protein synthesis rate was investigated in patients undergoing elective minor surgery and major surgery before and immediately after surgery. Minor surgery did not have an impact on muscle protein synthesis rate, as expected. However, muscle protein synthesis rate following major surgery was also unaltered. Intensive care patients have an on average normal muscle protein synthesis rate but with a larger variation than in healthy individuals. In order to evaluate if artefacts or muscle tissue heterogeneity can explain this large scatter, muscle protein synthesis rate was determined simultaneously in both legs of ICU patients. Muscle protein synthesis rate was on average normal, and similar in the two legs. The variation between the legs was smaller than the variation between individuals and muscle morphology revealed no local differences. In summary the immediate effect of surgical trauma on muscle protein synthesis rate was not demonstrated to be size dependent. The decrease in muscle protein synthesis rate observed following medium size abdominal surgery could not be prevented by continuous and ongoing conventional total parenteral nutrition. In ICU patients glutamine supplemented TPN normalized plasma glutamine concentrations but muscle glutamine concentrations were not affected and no effect were seen on muscle protein synthesis. No local differences were found in leg muscle morphology of ICU patients, confirming earlier results showing a large variation in muscle protein synthesis rate between individuals. ICU patients have an on average normal muscle protein synthesis rate with a low intra-individual variation.