Muscle mitochondrial activity increases rapidly after an endotoxin challenge in human volunteers.
BACKGROUND
Mitochondrial derangements in muscle of patients suffering from sepsis have been established in several studies and have been related to muscle dysfunction and organ failure. It is not possible to study the early phase of sepsis in patients; therefore, we used a human endotoxaemia model to study the effect of early sepsis on muscle mitochondria.


METHODS
Seven healthy male volunteers received a standardised endotoxin challenge. Muscle biopsies were obtained immediately before the challenge, and at 2 and 4 h following the endotoxin challenge. The muscle biopsies were analysed for maximal activities of citrate synthase and complexes I and IV of the respiratory chain. In addition, total and mitochondrial superoxide dismutase (SOD) activities were analysed. The concentrations of ATP, creatine phosphate and lactate were analysed to assess the cellular energy status. Total and phosphorylated AMP-activated protein kinase (AMPK-P), a key regulator in intracellular energy metabolism, was measured.


RESULTS
Activities of citrate synthase and complex I were significantly increased 2 h after the endotoxin challenge. SOD activities were unaffected by the endotoxin challenge. No changes in ATP, creatine phosphate or lactate were observed. Neither total nor AMPK-P changed.


CONCLUSIONS
An endotoxin challenge given to healthy volunteers rapidly increases mitochondrial enzyme activity in skeletal muscle. The results of this human model indicate that possibly early during sepsis, mitochondrial activity might be increased in contrast to what has been shown in the later phases of sepsis. It is possible that this early activation leads to exhaustion of the mitochondria and a decreased function later during sepsis.
Fredriksson
K
K
Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Sweden.
Fläring
U
U
Guillet
C
C
Wernerman
J
J
Rooyackers
O
O
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D001706:Biopsy; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D004731:Endotoxins; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D055372:AMP-Activated Protein Kinases