Brain metabolic and ionic responses to systemic hypoxia in the newborn dog in vivo

Newborns are less sensitive than adults to hypoxic/ischemic injury. However, research into the mechanism of the newborn's relative resistance to reduced brain oxygen levels is relatively scarce, and the time-scale for the disappearance of resistance is not known. The multiprobe assembly (MPA) has enabled us to examine the resistance of puppies at various ages to hypoxia via continuous, simultaneous, on-line measurement of various ionic, metabolic and electrical parameters from the cerebral cortex. The parameters measured included electrocorticogram (ECoG), direct current (DC) steady state potential, extracellular potassium (K(e)⁺) and calcium ion concentrations and intra-mitochondrial Nicotine amide adenine dinucleotide NADH redox levels. These parameters were measured under various degrees of hypoxia (fraction of inspiration oxygen was between 0-10%) in 6-h-old to 24-week-old puppies (n = 44). Sensitivity to hypoxia increased with age, being expressed in the leakage of potassium ions out of the cells (0.3 ± 0.07mM in the younger puppies and 3.0 ± 1.3 mM in the older puppies) following an increase in intra-mitochondrial NADH redox levels. Potassium ion (K(e)⁺) leakage was apparently due to depleted energy stores resulting from an impairment in the balance between oxygen supply and demand. Although the overall effect was similar, the kinetics of these changes were much faster in the older puppies. The time to initial increase of extracellular K⁺ was 2.5 ± 0.1 min in the younger puppies and 0.9 ± 0.1 min in the older puppies. The time to maximum increase of NADH was 3.24 ± 0.2 min in the younger puppies and 1.4 ± 0.1 min in the older puppies. Our results indicate that the older puppies utilize the existing oxygen faster than the younger puppies. It is concluded that the increased resistance of newborn puppies to hypoxia is due to intrinsic properties of the brain itself, like the ability of the membrane to maintain ionic homeostasis.