The objective of the present study was to explore whether a
free radical spin trap agent,
alpha-phenyl-N-tert-butyl nitrone (PBN), influences bioenergetic failure induced in the 20-day-old fetal brain by 30 min of intrauterine
ischemia in Wistar rats. Fetal brains were frozen in situ at the end of
ischemia and after 1, 2, and 4 h of recirculation for analysis of
ATP,
ADP,
AMP, and
lactate. PBN or vehicle was given 1 h after recirculation. Tissue
oxygen tension was evaluated in placental and fetal cerebral tissues throughout the whole periods of 30 min of
ischemia and 4 h of recirculation.
Ischemia was associated with a decrease in
ATP concentration and an increase in
lactate concentration (p < 0.001). Recirculation (1 and 2 h) led to a recovery of
ATP concentration, but continued reflow (4 h) was associated with a secondary deterioration of high-energy
phosphates (p < 0.01).
Lactate concentration increased during this recovery period. This deterioration was prevented by PBN (p < 0.05). After 30 min of
ischemia, tissue
oxygen tension in placenta and fetal brain decreased to about 30% and 50% of control, respectively. However, recirculation brought about a recovery of
oxygen delivery. The results indicate that although during the early time period after
ischemia fetal cerebral energy metabolism is maintained by an acceleration of the anaerobic glycolytic rate, secondary deterioration of cellular bioenergetic state develops in the immature fetal brain. This deterioration may be due to
mitochondrial dysfunction, which may be induced by
oxygen-derived
free radicals, and not by compromised microcirculation.