Influence of aging on cerebral derangement by acute severe hypoxia during hypovolemic hypotension

In synaptosomes isolated from the motor area of the cerebral cortex of beagle dogs and incubated in Krebs-Henseleit-Hepes buffer (for 10 min at 24°C), the energetic state was defined by the balance of the labile phosphates (ATP, ADP, AMP, and creatine phosphate), the redox state of the intramitochondrial NAD-couple, and the respiratory rate. By the experimental model utilized in the present research, it is possible to evaluate the potential synaptosomal damage induced by the in vivo hypoxic insult. Aging affects the phosphorylation state of the posthypoxic incubated synaptosomes. Although the oxygen consumption rate is the same in the synaptosomal fractions from the motor area of hypoxic beagle dogs of different ages, the cytochrome c and a contents are lower in the preparations from older brains. This points to higher activity of cytochromes in the synaptosomes from “mature” and “senescent” hypoxic animals. In dogs of different ages, hypoxia lowers the respiration of the synaptosomes but aging affects the oxygen consumption rates only in post-hypoxic synaptosomes incubated with succinate. In synaptosomes isolated from older hypoxic brains, the free energy utilized for the synthesis of two moles of ATP (ΔG_ATP) is progressively lower than that released upon the transfer of electrons from the NADH to cytochrome c (ΔG_{ox red}).