Additive Effects of Pentobarbital and Halothane to Inhibit Synthesis of Lung Proteins

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Abstract
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 .mu.M phenylalanine, 5.6 mM glucose and 4.5% 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%) at a pentobarbital concentration of 324 .mu.g/ml. Halothane (1-4% 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 1-4% were equally effective. When lungs were exposed to a combination of pentobarbital (100 .mu.g/ml) and halothane (1%) at doses which had no effect when given alone, protein synthesis was inhibited 35% (P < 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 .mu.g/ml), with or without 4% halothane, was fully reversible. A similar inhibitory effect of pentobarbital was observed in perfused rat hearts.