Sepsis alters skeletal muscle energetics and membrane function

The effects of sepsis on skeletal muscle energetics and membrane function are poorly understood, and the time course of changes in energy metabolism are unclear. To clarify these relationships, high energy phosphate ratios, intracellular pH, and phosphocreatine breakdown rates were measured in vivo in the gastrocnemius muscle of adult male Wistar rats after cecal ligation and puncture or sham operation with ³¹P magnetic resonance spectroscopy. Adenosine triphosphate (ATP) concentration and Na⁺-K⁺ ATPase and creatine kinase activities were determined in vitro. Within 24 hours, Na⁺-K⁺ ATPase activity increased by 60% in rats with cecal ligation and puncture, all of which had positive bacterial cultures, as compared to none of the sham- operated controls. Phosphocreatine/ATP ratios decreased by 20% in association with a quantitatively similar increase in phosphocreatine breakdown (9.7 ± 0.5 vs 11.9 ± 0.5 μmoles/gm wet wt/sec; p = 0.01). ATP concentrations were maintained, and intracellular pH did not change significantly. In this model, changes in phosphocreatine breakdown were not related to total creatine kinase activity, which did not change significantly, or increases in adenosine 5'-diphosphate (ADP) concentration (62 ± 8 vs 92 ± 8 μmol/L; p = 0.02). Thus, in early sepsis before a measurable decrease in pH occurs, ATP is utilized at an increased rate to help maintain ionic balance and/or to support other metabolic processes. Phosphocreatine stores are used to buffer ATP concentrations.