Potentiation of decreased pyruvate dehydrogenase activity by inflammatory stimuli in sepsis

The effect of inflammation and chronic sepsis on the activity of pyruvate dehydrogenase complex (PDH) in skeletal muscle was investigated in rats. Inflammation was induced by the placement of a catheter in the carotid artery. Sepsis was induced by repeated (every 48 hr) injections of an inoculum composed of Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis organisms into a preformed subcutaneous abscess. Hindlimb muscle was sampled 7 or 14 days following the initial injection of the inoculum into the abscess. Total PHD activity was not altered by any of the conditions examined. There were no differences in the proportion of active PDH complex after 7 days in any of the conditions examined. In contrast, 14 days after the initial bacterial injection, the concentration of active PDH complex in skeletal muscle was reduced by 50% in the septic rats. The combination of intravascular catheterization and infection resulted in a further decrease in the concentration of active PDH complex. The decreased concentration of active PDH complex was associated with increased plasma lactate concentrations in septic rats. Catheterization exacerbated the rise in plasma lactate in sepsis. In this model of chronic sepsis, the magnitude of the hyperlactatemia and the inhibition of the PDH complex in skeletal muscle appear dependent upon the length of time of the septic insult and are potentiated by addition of an intravascular focus of inflammation.