Abstract

The role of free radicals in septic-shock-associated tissue injury and the mechanisms underlying the generation of free radicals in sepsis was investigated in a primate model using electron spin-trapping techniques paired with physiological measurements. Baboons were administered the spin trap resonance (ESR) spectroscopy and spin-trapping techniques paired with physiological measurements. Baboons were administered the spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) during infusions of live Escherichia coli(E. coli) with or without challenge with tumor necrosis factor (TNF). ESR spectra suggesting the trapping of carbon-centered and oxygen-centered radicals were detected in liver lipid extracts of E. coli infused animals which exhibited patholophysiological changes indicative of sepsis. In animals demonstrating a toxic response to E. coli, TNF challenge appeared to intensify the ESR signal observed. The data provide evidence of free radical production during sepsis and suggest a role for TNF in the production of these radicals.

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