Short therapeutic window for nifedipine in transient intrauterine ischemia in fetal rat brain.
The aim of this study was to explore whether nifedipine influences the secondary deterioration of cerebral mitochondrial function after transient intrauterine ischemia in fetal rats. Intrauterine ischemia was induced by a 30-min occlusion of the right uterine artery at 20 days of gestation in Wistar rats. Nifedipine (1 mg kg(-1)) or vehicle was injected subcutaneously before the onset of ischemia or 1 h after the start of recirculation. Fetuses were delivered by cesarean section at the end of ischemia (n=6 with vehicle; n=6 with nifedipine pretreatment) or at 4 h of recirculation (n=6 with vehicle; n=6 with nifedipine pretreatment; n=6 with nifedipine posttreatment), and the cerebral mitochondrial respiration was measured polarographically. Tissue oxygen tension was evaluated in placental and fetal cerebral tissues (n=5 with vehicle; n=5 with nifedipine pretreatment). The vehicle treated animals showed a significant decrease in mitochondrial activities at the end of ischemia and 4 h of recirculation. Nifedipine attenuates the secondary deterioration at 4 h of recirculation when given just prior to ischemia, but had no neuroprotective activity when given 1 h after the start of recirculation. Nifedipine pretreatment had no influence on oxygen delivery in placenta and fetal cerebrum during and after ischemia. Despite the short therapeutic window, the treatment of nifedipine attenuates the secondary deterioration of cerebral mitochondrial function after transient intrauterine ischemia in fetal rats when given just prior to ischemia.
Nakai
Akihito
A
Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan. nakai-3@nms.ac.jp
Shibazaki
Yukino
Y
Taniuchi
Yoshinari
Y
Nagano
Reiko
R
Oya
Atsuko
A
Koshino
Tatsuo
T
Araki
Tsutomu
T
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism
D009543:Nifedipine