Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis-induced multiple organ failure.
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 compared with 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 twofold decrease in mitochondrial content in intensive care unit 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.
Fredriksson
Katarina
K
Department of Anesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Sweden. katarina.fredriksson@ki.se
Hammarqvist
Folke
F
Strigård
Karin
K
Hultenby
Kjell
K
Ljungqvist
Olle
O
Wernerman
Jan
J
Rooyackers
Olav
O
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002950:Citrate (si)-Synthase / Q000378:metabolism; D016638:Critical Illness; D042967:Electron Transport Complex I / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D007366:Intercostal Muscles / Q000378:metabolism* / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism; D007866:Leg; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009102:Multiple Organ Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010725:Phosphocreatine / Q000378:metabolism; D018805:Sepsis / Q000150:complications / Q000378:metabolism* / Q000473:pathology
D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D042967:Electron Transport Complex I