Mitochondrial function in sepsis: acute phase versus multiple organ failure.

Abstract

To describe temporal changes in mitochondrial function during the septic process, including the recovery phase. Literature review. Clinical studies and laboratory models. Biochemical and ultrastructural mitochondrial abnormalities have been recognized in in vivo, ex vivo, and in vitro laboratory models of sepsis for >30 yrs. Short-term models show variable effects on mitochondrial function and structure; this is likely related to differences in model design, including species, organs studied, degree of septic insult, and degree of resuscitation. Longer-term models more consistently reveal mitochondrial dysfunction and damage. There is a rebound increase in oxygen consumption and resting energy expenditure in the recovery phase of sepsis. This could reflect mitochondrial recovery (biogenesis) that may restore the energy supply needed to fuel restorative metabolic processes and enable patient survival. Mitochondrial dysfunction seems to be intrinsically involved in the pathogenesis of multiple organ failure. As a consequence of a progressive decrease in energy availability, metabolism must decrease or the cell will die. The interplay between adenosine 5'-triphosphate supply and demand, dictated by the degree of mitochondrial dysfunction and the level of metabolic shutdown (analogous to a hibernation-type response), seems to be crucial in determining outcome. Further studies are needed to confirm this hypothesis.