Maturation of the Mitochondrial Redox Response to Profound Asphyxia in Fetal Sheep

摘要: Fetal susceptibility to hypoxic brain injury increases over the last third of gestation. This study examined hypothesis that this is associated with impaired mitochondrial adaptation, as measured by more rapid oxidation cytochrome oxidase (CytOx) during profound asphyxia. Methods: Chronically instrumented fetal sheep at 0.6, 0.7, and 0.85 gestation were subjected either 30 min (0.6 gestational age (ga), n = 6), 25 (0.7 ga, 27) or 15 (0.85 17) complete umbilical cord occlusion. EEG, cerebral impedance (to measure swelling) near-infrared spectroscopy-derived intra-cerebral oxygenation (ΔHb HbO2 – Hb), total hemoglobin (THb) CytOx redox state monitored continuously. Occlusion was profound, fall in ΔHb all groups a plateau from 6 min, greatest ga compared 0.6 0.7 (p<0.05). THb initially increased ages, rise (p<0.05), followed progressive 7 groups. further, delayed increase preterm fetuses, but striking group after Cerebral (a cytotoxic edema) earlier rapidly greater In conclusion, cortical asphyxia maturation consistent increasing dependence on oxidative metabolism leading onset neural energy failure before systemic hypotension.