Effect of alpha-phenyl-N-tert-butyl nitrone (PBN) on fetal cerebral energy metabolism during intrauterine ischemia and reperfusion in rats.
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.
Nakai
A
A
Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan.
Asakura
H
H
Taniuchi
Y
Y
Koshino
T
T
Araki
T
T
Siesjö
B K
BK
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D003497:Cyclic N-Oxides; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D009589:Nitrogen Oxides / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D014599:Uterus / Q000098:blood supply*
D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; D010100:Oxygen