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Paper
December 1998

Skeletal Muscle Phosphocreatine Depletion Depresses Myocellular Energy Status During Sepsis

Author Affiliations

From the Laboratory for Surgical Metabolism and Nutrition, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.

Arch Surg. 1998;133(12):1316-1321. doi:10.1001/archsurg.133.12.1316
Abstract

Objective  To determine the effects of phosphocreatine (PCr) depletion on myocellular energetics.

Design  Randomized controlled study.

Setting  University laboratory.

Materials  Thirty-eight adult male Wistar rats (110-121 g).

Methods  The poorly metabolized creatine analogue β-guanidinopropionic acid, (β-GPA, 2% of a gel diet) was fed to the rats for 14 days to replace (75%) endogenous PCr stores before cecal ligation and puncture (CLP). Rats were randomized to receive sham operation and gel diet (sham-gel group [n=10]), sham operation and β-GPA diet (sham–β-GPA group [n=9]), CLP and gel diet (CLP-gel group [n=10]), and CLP and β-GPA diet (CLP–β-GPA group [n=9]). On day 14, all animals underwent operation. Twenty-four hours later, in vivo phosphorus 31–labeled magnetic resonance spectroscopy (31P-MRS) of the gastrocnemius muscle was performed. Muscle samples were collected to determine enzyme activities of β-hydroxyacyl-CoA dehydrogenase, 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–β-GPA animals had altered bioenergetics, CLP–β-GPA rats experienced a greater deterioration of energy state compared 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 sepsis, which is worsened by PCr depletion. These changes support the contention that PCr plays an important role as an ATP buffer during systemic infection.

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