Skeletal muscle phosphocreatine depletion depresses myocellular energy status during sepsis

Tirso M. Lara, Michael S. Wong, Jan Rounds, Malcolm K. Robinson, Douglas W. Wilmore, Danny O. Jacobs

Research output: Contribution to journalArticle

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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 (110121 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 βGPA diet (sham-β-GPA group [n = 9]), CLP and gel diet (CLP-gel group [n = 101), and CLP and β-GPA diet (CLPβ-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 shamβ-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.

Original languageEnglish (US)
Pages (from-to)1316-1321
Number of pages6
JournalArchives of Surgery
Volume133
Issue number12
DOIs
StatePublished - 1998
Externally publishedYes

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Phosphocreatine
Punctures
Ligation
Sepsis
Skeletal Muscle
Gels
Diet
Creatine
Adenosine Triphosphate
Citrate (si)-Synthase
Phosphofructokinases
Enzymes
Coenzyme A
Adenosine Diphosphate
Phosphorus
Energy Metabolism
Wistar Rats
Buffers
Oxidoreductases
Hydrolysis

ASJC Scopus subject areas

  • Surgery

Cite this

Lara, T. M., Wong, M. S., Rounds, J., Robinson, M. K., Wilmore, D. W., & Jacobs, D. O. (1998). Skeletal muscle phosphocreatine depletion depresses myocellular energy status during sepsis. Archives of Surgery, 133(12), 1316-1321. https://doi.org/10.1001/archsurg.133.12.1316

Skeletal muscle phosphocreatine depletion depresses myocellular energy status during sepsis. / Lara, Tirso M.; Wong, Michael S.; Rounds, Jan; Robinson, Malcolm K.; Wilmore, Douglas W.; Jacobs, Danny O.

In: Archives of Surgery, Vol. 133, No. 12, 1998, p. 1316-1321.

Research output: Contribution to journalArticle

Lara, TM, Wong, MS, Rounds, J, Robinson, MK, Wilmore, DW & Jacobs, DO 1998, 'Skeletal muscle phosphocreatine depletion depresses myocellular energy status during sepsis', Archives of Surgery, vol. 133, no. 12, pp. 1316-1321. https://doi.org/10.1001/archsurg.133.12.1316
Lara, Tirso M. ; Wong, Michael S. ; Rounds, Jan ; Robinson, Malcolm K. ; Wilmore, Douglas W. ; Jacobs, Danny O. / Skeletal muscle phosphocreatine depletion depresses myocellular energy status during sepsis. In: Archives of Surgery. 1998 ; Vol. 133, No. 12. pp. 1316-1321.
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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 (110121 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 βGPA diet (sham-β-GPA group [n = 9]), CLP and gel diet (CLP-gel group [n = 101), and CLP and β-GPA diet (CLPβ-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 shamβ-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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AU - Jacobs, Danny O.

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AB - 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 (110121 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 βGPA diet (sham-β-GPA group [n = 9]), CLP and gel diet (CLP-gel group [n = 101), and CLP and β-GPA diet (CLPβ-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 shamβ-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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