Association Between Mitochondrial Dysfunction and Severity and Outcome of Septic Shock

摘要: Summary: Background: Sepsis-induced multiple organ failure is the major cause of mortality and morbidity in critically ill patients. However, precise mechanisms by which this dysfunction caused remain to be elucidated. We others have shown raised tissue oxygen tensions septic animals human beings, suggesting reduced ability organs use oxygen. Because ATP production mitochondrial oxidative phosphorylation accounts for more than 90% total consumption, we postulated that results failure, possibly due nitric oxide, known inhibit respiration vitro produced excess sepsis. Methods: did skeletal muscle biopsies on 28 patients within 24 h admission intensive care, nine control undergoing elective hip surgery. The biopsy samples were analysed respiratory-chain activity (complexes I–IV), concentration, glutathione (an intracellular antioxidant) nitrite/nitrate concentrations (a marker oxide production). Findings: Skeletal significantly lower 12 with sepsis who subsequently died 16 survived (p=0·0003) controls (p=0·05). Complex I had a significant inverse correlation norepinephrine requirements proxy shock severity, p=0·0003) (p=0·0004), positive (p=0·006) (p=0·03). Interpretation: In patients, found an association between overproduction, antioxidant depletion, dysfunction, decreased relate eventual outcome. These data implicate bioenergetic as important pathophysiological mechanism underlying multiorgan dysfunction.