Mitochondrial death in sepsis: a failed concept.
The concept of early selective mitochondrial injury has been proposed to explain the global metabolic dysfunction observed in the septic state. A two phase study was undertaken to test the validity of this hypothesis. In the initial phase, an endotoxin shock model was employed in the rat to delineate the function of skeletal muscle mitochondria. Mitochondrial function was determined polarimetrically, comparing state three and state four rates, respiratory control index (RCI) and ADP:O ratios. No significant alteration in these parameters was observed in the endotoxic state. Phase II of the study was designed to investigate mitochondrial function in a bacterial peritonitis rat model. Both liver and skeletal muscle mitochondrial function were determined to control for possible alterations in liver metabolism. Neither muscle nor liver mitochondria exhibited functional impairment during sepsis. We conclude from this study that neither endotoxemia nor peritonitis selectively "kills" mitochondria as previously suggested.
D000818:Animals; D004927:Escherichia coli Infections / Q000378:metabolism; D007239:Infections / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D008930:Mitochondria, Liver / Q000378:metabolism / Q000502:physiology; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000502:physiology; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D010538:Peritonitis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000378:metabolism