In vivo responses of mitochondrial redox levels to Eschericia coli bacteremia in primates
Septic shock is characterized by multifactorial and interrelated defects in hemodynamic function and metabolism. Systemic derangements in hemodynamic parameters, oxygen uptake, and substrate preference at various stages of septic shock have been characterized; however, sepsis-induced alterations in the coupling of oxygen delivery to oxygen use and energy metabolism are poorly understood at the tissue level in vivo. In this study, we investigated mechanisms of disordered oxygen metabolism in intact brain and skeletal muscle in the baboon during early Escherichia coli sepsis. Sepsis-related changes in hemodynamic, oxygen use, and metabolic parameters were correlated with changes in vascular function, local oxygen supply, and mitochondrial redox status, assessed noninvasively at the tissue level using near-infrared (NIR) spectroscopy. The NIR data indicate that sepsis is associated with early disturbances of intramitochondrial redox state in intact skeletal muscle and brain tissues, as well as derangements of vascular autoregulation in the skeletal muscle. These responses occur within an hour of the onset of injury, and before changes in cardiac output or the appearance of hypotension. These findings were made using simple maneuvers designed to be applied to humans at various hemodynamic and metabolic stages of septic shock. This approach should be valuable in providing a better understanding of mechanisms of injury in sepsis, and the action of various therapeutic interventions at the tissue level in vivo. © 1990.
Griebel, JA; Fracica, PJ; Piantadosi, CA
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