Skeletal muscle phosphocreatine depletion depresses myocellular energy status during sepsis

Objective: To determine the effects of phosphocreatine (PCr) depletion on m yocellular energetics. Design: Randomized controlled study. Setting: University laboratory. Materials: Thirty-eight adult male Wistar rats (110-121 g). Methods: The poorly metabolized creatine analogue beta-guanidinopropionic a cid, (beta-GPA, 2% of a gel diet) was fed to the rats for 14 days to replac e (75%) endogenous PCr stores before cecal ligation and puncture (CLP). Rat s were randomized to receive sham operation and gel diet (sham-gel group [n = 10]), sham operation and beta-GPA diet (sham-beta-GPA group [n = 9]), CL P and gel diet (CLP-gel group [n = 10]), and CLP and beta-GPA diet (CLP-bet a-GPA group [n = 9]). On day 14, all animals underwent operation. Twenty-fo ur hours later, in vivo phosphorus 31-labeled magnetic resonance spectrosco py (P-31-MRS) of the gastrocnemius muscle was performed. Muscle samples wer e collected to determine enzyme activities of beta-hydroxyacyl-CoA dehydrog enase, phosphofructokinase, citrate synthase, and the metabolites adenosine triphosphate (ATP), PCr, inorganic phosphate, and creatine. Free adenosine diphosphate levels, the phosphorylation potential, and free energy change of ATP hydrolysis were then calculated. Results: All animals undergoing CLP but no controls had positive results of blood cultures. Although sham-beta-GPA animals had altered bioenergetics, CLP-beta-GPA rats experienced a greater deterioration of energy state compa red with CLP-gel controls. Glycolytic and oxidative enzyme activities were not significantly different between groups and therefore could not explain the observed differences. Conclusions: There is an overall decrease in energy availability during sep sis, which is worsened by PCr depletion. These changes support the contenti on that PCr plays an important role as an ATP buffer during systemic infect ion.