J. Arnold et al., INCREASED WHOLE-BODY PROTEIN BREAKDOWN PREDOMINATES OVER INCREASED WHOLE-BODY PROTEIN-SYNTHESIS IN MULTIPLE ORGAN FAILURE, Clinical science, 84(6), 1993, pp. 655-661
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.