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Am J Physiol Endocrinol Metab (June 27, 2006). doi:10.1152/ajpendo.00218.2006
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Submitted on May 8, 2006
Accepted on June 22, 2006

Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis induced multiple organ failure

Katarina Fredriksson1*, Folke Hammarqvist2, Karin Strigard2, Kjell Hultenby3, Olle Ljungqvist4, Jan Wernerman5, and Olav Rooyackers5

1 Anaesthesiology and Intensive Care, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
2 Gastrocentrum, Surgery, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
3 Clinical Research Center, Karolinska University Hospital Huddinge, Karolinska Instiutet, Stockholm, Sweden
4 Center for Gastrointestinal Disease, Ersta Hospital, Karolinska Institutet, Stockholm, Sweden
5 Anaesthesiology and Intensive Care, Karolinska University Hospital Huddinge, Karolinska institutet, Stockholm, Sweden

* To whom correspondence should be addressed. E-mail: katarina.fredriksson{at}ki.se.

Critically ill patients treated for multiple organ failure often develop muscle dysfunction. Here we test the hypothesis that mitochondrial and energy metabolism are deranged in leg and intercostal muscle of critically ill patients with sepsis induced multiple organ failure. Ten critically ill patients suffering from sepsis induced multiple organ failure and requiring mechanical ventilation were included in the study. A group (n=10) of metabolically healthy age and sex-matched patients undergoing elective surgery were used as controls. Muscle biopsies were obtained from the vastus lateralis (leg) and intercostal muscle. The activities of citrate synthase and mitochondrial respiratory chain complexes I and IV and concentrations of ATP, creatine phosphate and lactate were analyzed. Morphological evaluation of mitochondria was performed by electron microscopy. Activities of citrate synthase and complex I were 53 and 60% lower respectively in intercostal muscle of the patients, but not in leg muscle in comparison with the controls. The activity of complex IV was 30% lower in leg muscle, but not in intercostal muscle. Concentrations of ATP and creatine phosphate were respectively 40 and 34% lower and lactate concentrations were 43% higher in leg muscle, but not in intercostal muscle. We conclude that both leg and intercostal muscle show a two-fold decrease in mitochondrial content in ICU patients with multiple organ failure, which is associated with lower concentrations of energy rich phosphates and an increased anaerobic energy production in leg muscle, but not in intercostal muscle.




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