Amrinone prevents muscle protein wasting during chronic sepsis

The time course for the effects of sepsis on rates of protein synthesis, RNA contents, and translational efficiencies was measured in mixed muscles of rat hindlimb perfused in vitro 3, 5, and 10 days after induction of sepsis. Furthermore, the effect of daily injections of amrinone (5 mg.kg-1.day-1) on muscle protein synthesis was investigated. On day 3 of sepsis, decreased rates of protein synthesis in muscle from untreated septic animals or septic rats treated with amrinone resulted from a reduced food intake. When food intake became normalized to control after 5 days, rates of protein synthesis in untreated septic rats remained depressed. Treatment of septic animals with amrinone for 5 days prevented the sepsis-induced inhibition of protein synthesis by abolishing the inhibition of peptide-chain initiation and restoring translational efficiency to control values. In contrast, amrinone treatment of control rats for 5 days did not cause an accretion of muscle protein or augment protein synthesis. Ten days after induction of sepsis, there were no differences in rates of protein synthesis, RNA content, or translational efficiency in septic animals compared with control or amrinone-treated septic rats. Thus, amrinone prevented the sepsis-induced abnormalities in skeletal muscle protein synthesis.