OXYGEN RADICALS AND NITRIC-OXIDE IN SEPSIS

Accumulation and stimulation of PMN-leukocytes, enhanced prostaglandin metabolism and tissue hypoxia lead to high concentrations of oxygen radicals and their metabolites in septic shock. Synchroneously, excessive high concentrations of nitric oxide are found, most likely due to the stimulation of its inducible synthetase. Oxygen radicals seem to be attributable for the irreversible tissue damage leading to multiple organ failure in sepsis. High concentrations of nitric oxide induce the typical macro- and microcirculatory derangements normally seen in sepsis. Both mediators are present in the early phase of sepsis and seem to influence the course of disease. Therapeutic interventions such as scavenger therapy or inhibition of the inducible NO-synthetase are promising. The results of the first clinical therapeutic studies, however, were not always conclusive. It is still unclear which scavenger and which inhibitor should be given when and in which dosage in order to improve the outcome of sepsis and septic shock. Furthermore, it remains unclear to which extend oxygen radicals and nitric oxide react with each other, thus possibly potentiating their effects. The open questions still warrant further research and may lead to new therapeutic options improving the morbidity and mortality of this severe disease.