Rolul oxidului nitric în hipoxia citopatică – disfuncţia mitocondrială în sepsis

Abstract

The sepsis syndromes and their sequel, specifically multiple organ dysfunction syndromes (MODS), represent the leading cause of death in adult general ICUs. Aggressive efforts to improve systemic O2 delivery by administering intravenous fluids packed with red blood cells and inotropic agents can improve outcomes for patients with septic shock. However, efforts to improve systemic O2 delivery later in the course of sepsis are at best ineffective, and at worst deleterious. If improving perfusion and O2 delivery in patients with established sepsis fails to improve survival or prevent organ system dysfunction, one could hypothesize that cellular energy is deranged in sepsis not just because O2 delivery is impaired but also because the cell's ability to use available O2 is compromised. The term used to describe such intrinsic derangement in cellular respiration is cytopathic hypoxia. In cytopathic hypoxia, an acquired defect in oxidative phosphorylation prevents cells from using molecular oxygen for adenosine triphosphate production potentially causing sepsis-induced organ dysfunction, and supports a link between mitochondrial dysfunction and pathologic metabolic events in septic shock. It has been shown that mitochondria have their own nitric oxide synthase (mtNOS), which produces NO constitutively. This NO modulates mitochondrial function. It remains unclear, however, whether cytopathic hypoxia is an epiphenomenon or a pathophysiological mechanism that actually contributes to organ dysfunction and, ultimately, mortality in patients with sepsis or septic shock.