CEREBRAL HISTOLOGIC AND ELECTROCORTICOGRAPHIC CHANGES AFTER ASPHYXIA IN FETAL SHEEP

Asphyxia can cause neurologic damage in the fetus, but there are few data relating severity or duration of asphyxia to the degree of cerebral damage. We report cerebral histologic and electrophysiologic changes after asphyxia in chronically instrumented late-gestation fetal sheep. We reduced uterine blood flow to produce an ascending aortic blood oxygen content < 1.5 mM for either 30 or 60 min (n = 13). In a subsequent protocol (n = 6), if full occlusion of the common uterine artery for 15 min did not reduce the EEG voltage to less than 20% of baseline, supplementary maternal hypoxia was added for a maximum of 120 min. Histologic outcome was assessed 3 d postinsult. Uterine artery occlusion resulted in severe hypoxemia, hypercarbia, acidosis, and an initial hypertension and bradycardia. Eight of 14 surviving fetuses showed neuronal damage, with greatest loss in the parasagittal cortex, striatum, and the CA 1/2 region of the hippocampus. Neuronal damage was strongly associated with the percentage of decrease in blood pressure during the insult (r = 0.75, p < 0.005) but not with the degree of hypoxia. No other factor was independently predictive, but, when considered separately, pH (r = 0.54; p < 0.05) and loss of intensity of the EEG (r = 0.61, p < 0.02) at the end of asphyxia were also correlated with outcome. The pH fell to < 7.0 in six of eight fetuses with damage, whereas it remained > 7.0 in five of six without damage (p < 0.05). We conclude that severe intrauterine asphyxia for periods of 30 to 120 min can cause predominant parasagittal neuronal death and that this is associated with hypotension, severe metabolic acidosis, and suppression of EEG during the insult. These data are consistent with the suggestion that impairment of cerebral perfusion is a critical event in localizing cerebral damage during perinatal asphyxia.