AMRINONE PREVENTS MUSCLE PROTEIN WASTING DURING CHRONIC SEPSIS

The time course for the effects of sepsis on rates of protein synthesi s, RNA contents, and translational efficiencies was measured in mixed muscles of rat hindlimb perfused in vitro 3, 5, and 10 days after indu ction of sepsis. Furthermore, the effect of daily injections of amrino ne (5 mg.kg(-1).day(-1)) on muscle protein synthesis was investigated. On day 3 of sepsis, decreased rates of protein synthesis in muscle fr om untreated septic animals or septic rats treated with amrinone resul ted from a reduced food intake. When food intake became normalized to control after 5 days, rates of protein synthesis in untreated septic r ats 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 t ranslational efficiency to control values. In contrast, amrinone treat ment of control rats for 5 days did not cause an accretion of muscle p rotein or augment protein synthesis. Ten days after induction of sepsi s, there were no differences in rates of protein synthesis, RNA conten t, 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.