The duration of infection modifies mitochondrial oxidative capacity in rat skeletal muscle

Yasumitsu Mizobata, Derek Prechek, Jan D. Rounds, Vickye Robinson, Douglas W. Wilmore, Danny O. Jacobs

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Sepsis increases phosphocreatine (PCr) breakdown and reduces PCr stores in skeletal muscle. To determine if systemic infection impairs mitochondrial function, in vivo 13P magnetic resonance spectroscopy (31P MRS) studies of the gastrocnemius muscle were performed in virus-free male Wistar rats 24 or 48 hr after cecal ligation and 18-gauge needle single puncture (24°CLP, n = 16; 48°CLP, n = 15) or sham operation (24°SHAM, n = 18; 48°SHAM, n = 13). Physiologic saline (6 ml/100 g body wt) was injected intraperitoneally for fluid resuscitation. Water but no food was allowed in all animals. High resolution (8.45 Tesla) 31P MRS spectra, obtained at rest and during exercise using a 1.4-cm surface coil, were used to calculate PCr/ATP, PCr/Pi ratios, and intracellular pH. Steady-state muscle exercise was induced by supramaximal sciatic nerve stimulation at 10 Hz for 10 min. Recovery of PCr/(PCr + Pi) ratios after exercise was fitted to a monoexponential curve. The resultant function was used to calculate the half time for PCr recovery, the initial PCr resynthesis rate, and the maximal oxidative ATP synthesis rate, which reflect the rephosphorylation of ADP and are therefore measures of mitochondrial oxidative capacity. PCr/ATP ratios decreased by 12 and 11%, 24 and 48 hr after CLP, respectively. The PCr/Pi ratios decreased incrementally (7% in 24°CLP vs 23% in 48°CLP animals). Twenty-four hours after operation the half time for PCr recovery was shortened while the initial PCr resynthesis rate and maximal oxidative ATP synthesis rate were accelerated in CLP animals compared to controls. By 48 hr these indices of mitochondrial function were significantly slowed. Intracellular pH was well maintained in resting skeletal muscle in all animals. These data demonstrate that the reduction in high energy phosphate (PCr) stores observed during early sepsis are not secondary to mitochondrial dysfunction; in fact, the organelles' ability to rephosphorylate ADP is enhanced.

Original languageEnglish (US)
Pages (from-to)165-173
Number of pages9
JournalJournal of Surgical Research
Issue number1
StatePublished - Jul 1995
Externally publishedYes

ASJC Scopus subject areas

  • Surgery


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