Age dependence of steady state mitochondrial oxidative metabolism in the in vivo hypoxic dog brain

Mitochondrial bioenergetics were investigated in newborn, neonatal and adult dog brains during normoxia and hypoxia. The ratio of the rate of ATP synthesis to the maximum synthesis rate (V/V(max)), phosphorylation potential, [ADP] and PCr/Pi, were used to evaluate age related mitochondrial hypoxic tolerance. These indicators were calculated from the phosphorus compounds measured by in vivo ³¹P MRS quantitatively using ATP as an internal reference. Indicators and substrates of mitochondrial function, V/V(max), ADP, and Pi reached a peak value during the neonatal (3-21 days) period of development, suggesting that the oxidative metabolism of the neonate is more vulnerable to stress when compared to newborns and adults. Distinction among newborns and neonates became apparent during hypoxia. Newborns (0-2 days old) showed substantial tolerance by maintaining V/V(max) until exposure to severe hypoxia. Older neonates (3-21 days old) showed increases in V/V(max), [Pi] and [ADP] under less than severe conditions of hypoxia. Adults exhibited low V/V(max) values even during exposure to severe hypoxia, further indicating that mitochondrial oxidative processes are more stable in adults than in newborns and neonates. This study provides evidence that newborns and adults are more capable of maintaining mitochondrial function under conditions of minimal to moderate hypoxia than 3-21 day old neonates.