Oxygen-derived free radicals in the pathogenesis of experimental shock.

Oxygen-derived free radicals are naturally produced in biological systems mostly in ischemia and hypoxia related conditions. Imbalance of physiological defenses against oxygen-derived free radicals causes cellular damage. In our laboratory the role of oxygen radicals in the pathogenesis of circulatory shock was studied by exploiting the scavenging action of the spin-trapping compound phenyl-butyl-nitrone (PBN) in experiments concerning: (1) survival after shock, (2) microcirculatory derangements in endotoxin shock, (3) fluidity modifications of cell membranes during shock, (4) exhalation of ethane as non-invasive marker of shock. In some experiments the steroid methylprednisolone was used. Results showed that administration of PBN and of the steroid (1) ensures survival after otherwise lethal shock as confirmed by decreased ethane exhalation, (2) prevents microcirculatory troubles, (3) maintains stability of cell membranes. These findings strongly support the role of oxygen-derived free radicals in the pathogenesis and pathophysiology of circulatory shock.