INCREASED WHOLE-BODY PROTEIN BREAKDOWN PREDOMINATES OVER INCREASED WHOLE-BODY PROTEIN-SYNTHESIS IN MULTIPLE ORGAN FAILURE

1. Whole body protein turnover was measured using a primed-constant in fusion of L-[1-C-13]leucine with measurement of breath (CO2)-C-13 prod uction and plasma C-13 alpha-ketoisocaproate enrichment. Ten fasting p atients, requiring mechanical ventilation and suffering from multiple organ failure, and six healthy control subjects were studied. 2. Prote in breakdown and leucine removal from the plasma for protein synthesis were significantly higher in the patients than in the control subject s (P<0.01). In addition, leucine oxidation was almost 75% higher in th e patients than in the healthy control subjects (P<0.05). 3. Plasma co ncentrations of glucose, insulin and growth hormone were not different between the two groups, but those of glucagon (not significant), nora drenaline (P<0.05) and cortisol (P<0.01) were almost two- and three-fo ld higher in the patients than in the control subjects. 4. Mean energy expenditure, measured by indirect calorimetry, was 30% higher in the patients than in the healthy control subjects (P<0.01). 5. Combining t he data from both groups of subjects and using multiple regression ana lysis, cortisol was found to be the most significant predictor of (i) protein breakdown (48% of variance explained), (ii) leucine oxidation (69%) and (iii) hourly energy expenditure (54%). 6. The present invest igation using [C-13]leucine tracer methods demonstrated, in patients w ith multiple organ failure, that whole body protein breakdown and synt hesis increased concomitantly and were twice as high as rates measured in healthy control subjects. Of the hormones measured in the present study, cortisol appears to have the most significant effect on whole b ody protein turnover.