title: Short therapeutic window for nifedipine in transient intrauterine ischemia in fetal rat brain.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan. nakai-3@nms.ac.jp
authors.forename: Akihito
authors.initials: A
authors.lastname: Nakai
authors.forename: Yukino
authors.initials: Y
authors.lastname: Shibazaki
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Taniuchi
authors.forename: Reiko
authors.initials: R
authors.lastname: Nagano
authors.forename: Atsuko
authors.initials: A
authors.lastname: Oya
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Koshino
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Araki
mesh_terms: 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
chemical_list: D009543:Nifedipine