O₂ dependence of in vivo brain cytochrome redox responses and energy metabolism in bloodless rats

Oxygen-dependent changes in brain cytochrome redox state and cerebrocortical energy metabolism were evaluated in fluorocarbon-circulated rats at hematocrits of <1%. Redox levels of three respiratory chain cytochrome complexes, b, c, and a,a3 (cytochrome c oxidase), were continuously measured directly through the intact skulls of animals using reflectance spectrophotometry. The in vivo redox status of cytochromes at different F(i)O2 was directly compared with in vitro measured changes in cortical metabolites known to reflect energy production, i.e., glucose, pyruvate, lactate, phosphocreatine (PCr), ADP, and ATP. Lowering the F(i)O2 to < 1.0 caused the cytochromes to become increasingly more reduced. This was associated with increased tissue accumulation of pyruvate and lactate and a concomitant increase in the lactate/pyruvate (L/P) ratio. At F(i)O2 = -.6, cytochromes b, c, and a,a3 were 57, 53, and 46% reduced, respectively. There was no apparent cerebral energy deficit since changes in cortical PCr, ADP, and ATP concentrations were not statistically significant. Bloodless animals did not survive below F(i)O2 = 0.5. At this F(i)O2, the inability of the animals to sustain arterial pressure correlated (r = 0.87) with depletion of PCr and further increases in the L/P ratio (r = 0.66). Yet, the cortical ATP content was reduced by only 9% of control value. These data provide direct evidence that fluorocarbon emulsion (FC-43) sustains brain oxygenation and energy metabolism at high partial pressures of molecular O2. At lower F(i)O2, however, mitochondrial O2 uptake becomes limited as a function of decreasing perfusion pressure.

Duke Scholars

Author Claude Anthony Piantadosi Medicine, Pulmonary, Allergy, and Critical Care Medicine