[Shock: concepts for a definition]

The shock syndrome has been classically considered as a consequence of both decreased tissue perfusion and O2 supply; however, in some types of shock like septic or traumatic ones, regional blood flows may be increased. A decade ago, mitochondrial alterations consistent with uncoupling of oxidative phosphorylation were reported in either endotoxemic or hemorrhagic experimental shock or in humans. Recently, the discovery of nitric oxide (NO) and its increase in the shock state, has opened new perspectives in the understanding of this problem. Nitric oxide produces vasodilatation and, at the same time, increases the mitochondrial production of O2 active species like superoxide anion. Both radicals react to form a strong oxidant that is able to nitrate the phenolic rings of proteins: peroxynitrite. This effect leads to the impairment of the activities of different mitochondrial enzymes like succinate dehydrogenase and ATPase and the mitochondrial function and finally, to decreased energy levels and to multiorgan failure. The increase in NO release is due to the effects of circulating peptides and of increased adhesion of neutrophils to the endothelium and to the positive effects of inflammatory mediators like TNF-alpha and cytokines on inducible NOS (iNOS) expression in endothelium and tissues. It is suggested that the shock state is the consequence of an imbalance between NO and O2 and their metabolites.