Additive effects of pentobarbital and halothane to inhibit synthesis of lung proteins

The effect of pentobarbital on synthesis of lung proteins was investigated, both when administered alone and in combination with halothane. When rat lungs perfused in situ with Krebs-Henseleit bicarbonate buffer containing plasma levels of 19 amino acids, 690 microM phenylalanine, 5.6 mM glucose, and 4.5 per cent fraction V bovine serum albumin were exposed to pentobarbital, a dose-related inhibition of [14C]phenylalanine incorporation into protein was observed, with a maximal inhibition (74 per cent) at a pentobarbital concentration of 324 micrograms/ml. Halothane (1-4 per cent equilibrated with O2/N2/CO2, 4:15:1) also rapidly inhibited synthesis of lung proteins in a dose-dependent manner. At the maximally effective concentration of pentobarbital, exposure of the lungs to halothane enhanced the inhibition of protein synthesis; halothane concentrations ranging from 1 to 4 per cent were equally effective. Furthermore, when lungs were exposed to a combination of pentobarbital (100 micrograms/ml) and halothane (1 per cent) at doses which had no effect when given alone, protein synthesis was inhibited 35 per cent (P less than 0.001). Thus, the metabolic effects of the anesthetics were potentiated when the drugs were administered in combination. The inhibition of protein synthesis by pentobarbital (324 micrograms/ml), with or without 4 per cent halothane, was fully reversible. A similar inhibitory effect of pentobarbital was observed in perfused rat hearts.