Altered mitochondrial redox responses in gram negative septic shock in primates.

Published

Journal Article

Gram negative sepsis causes changes in oxygen supply-demand relationships. We have used a primate model of hyperdynamic gram negative sepsis produced by intravenous infusion of Escherichia coli (E. coli) to evaluate sepsis-induced alterations in mitochondrial oxidation-reduction (redox) state in muscle in vivo. The redox state of cytochrome a,a3, the terminal member of the intramitochondrial respiratory chain, was assessed in the intact forearm by near-infrared (NIR) spectroscopy. The muscle NIR data were compared to routine measures of oxygen delivery (DO2) and oxygen consumption (VO2). After E. coli infusion and fluid resuscitation, DO2 and VO2 showed minimal changes through 24 hr of sepsis. In contrast, changes in cytochrome a,a3 redox state evaluated by NIR occurred within a few hours and were progressive. Mitochondrial functional responses were correlated with structural changes observed on serial muscle biopsies. Gross morphological changes in muscle mitochondria were present in some animals as early as 12 hr, and, in most animals, by 24 hr. The morphologic changes were consistent with decreases in oxidative capacity as suggested by NIR spectroscopy. The NIR data also suggest that two mechanisms are operating to explain abnormalities in oxygen metabolism and mitochondrial function in lethal sepsis. These mechanisms include an early defect in oxygen provision to mitochondria that is followed by a progressive loss in functional cytochrome a,a3 in the muscle.

Full Text

Duke Authors

Cited Authors

  • Simonson, SG; Welty-Wolf, K; Huang, YT; Griebel, JA; Caplan, MS; Fracica, PJ; Piantadosi, CA

Published Date

  • May 1994

Published In

Volume / Issue

  • 43 / 1

Start / End Page

  • 34 - 43

PubMed ID

  • 7982271

Pubmed Central ID

  • 7982271

International Standard Serial Number (ISSN)

  • 0092-6213

Language

  • eng

Conference Location

  • United States