The effect of indomethacin on muscle and liver protein synthesis and on whole-body protein degradation during abdominal sepsis in the rat
H. R. Freund, J. H. James, R. LaFrance, L. S. Gallon, U. O. Barcelli, L. L. Edwards, S. N. Joffe, H. S. Bjornson and J. E. Fischer
It has been recently suggested that increased muscle protein degradation
during injury or infection is at least partially mediated by the increased
production of prostaglandin E2 in muscle, and some have suggested that
cyclooxygenase inhibitors might decrease protein loss in injured or septic
patients. In these experiments, fractional synthesis rates of mixed muscle
and liver protein and whole-body tyrosine flux were measured by constant
intravenous infusion of tyrosine labeled with carbon 14 in 17 rats with
sham operations and 15 severely septic rats with or without indomethacin
treatment (20 mg/kg/d). Fractional synthesis rates in muscle and liver were
decreased in late sepsis and were lowest in the septic group receiving
indomethacin. Unlike the fractional synthesis rate, which was affected by
indomethacin in septic rats only, tyrosine flux was significantly lower in
indomethacin-treated rats with sham operations and those with sepsis.
Although indomethacin reduced total-body protein breakdown during sepsis,
it was also associated with lower plasma albumin levels and with decreased
protein synthesis in muscle and liver at a time when the survival of the
septic host may be dependent on its ability to produce new protein for a
variety of vital functions. These results do not support the use of
indomethacin in sepsis.
