Succinate recovers mitochondrial oxygen consumption in septic rat skeletal muscle

Alessandro Protti, Jane Carré, Matthew T. Frost, Valerie Taylor, Raymond Stidwill, Alain Rudiger, Mervyn Singer

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: Mitochondrial dysfunction, particularly affecting complex I of the respiratory chain, could play a fundamental role in the development of multiple organ failure during sepsis. Increasing electron flow through complex II by addition of succinate may improve mitochondrial oxygen utilization and thus adenosine triphosphate production. DESIGN: Ex vivo animal study. SETTING: University research laboratory. SUBJECTS: Male adult Wistar rats. INTERVENTIONS: Fecal peritonitis was induced in conscious, fluid-resuscitated, hemodynamically-monitored rats. Sham-operation and naïve animals acted as controls. At 48 hrs, clinical severity was graded. Soleus muscle was taken for measurement of mitochondrial complex activities and oxygen consumption. The effect of glutamate plus malate (complex I substrates) and succinate (complex II substrate) on mitochondrial respiration was assessed. MEASUREMENTS AND MAIN RESULTS: In the presence of glutamate plus malate, mitochondrial oxygen consumption was abnormally low in skeletal muscle tissue from moderately-to-severely septic animals as compared with naïve and sham-operation controls (both p <.01). On addition of succinate, mitochondrial respiration was augmented in all groups, particularly in moderately-to-severely septic animals (39% ± 6% increase) as compared with naïve (11% ± 5%; p <.01) and sham-operation controls (10% ± 5%; p <.01). In the presence of succinate, mitochondrial oxygen consumption was similar between the groups. CONCLUSIONS: Succinate increases mitochondrial oxygen consumption in ex vivo skeletal muscle taken from septic animals, bypassing the predominant inhibition occurring at complex I. This warrants further exploration in vivo as a putative therapeutic modality.

Original languageEnglish
Pages (from-to)2150-2155
Number of pages6
JournalCritical Care Medicine
Volume35
Issue number9
DOIs
Publication statusPublished - Sep 2007

Keywords

  • Complex I
  • Mitochondria
  • Multiple organ failure
  • Oxygen consumption
  • Sepsis
  • Succinate

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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