Short therapeutic window for nifedipine in transient intrauterine ischemia in fetal rat brain

Brain Res. 2002 Jul 5;943(1):30-7. doi: 10.1016/s0006-8993(02)02501-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology
  • Female
  • Fetus / blood supply
  • Fetus / drug effects*
  • Fetus / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Nifedipine / pharmacology
  • Nifedipine / therapeutic use*
  • Oxygen Consumption / physiology
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Time Factors
  • Uterus / blood supply*
  • Uterus / drug effects
  • Uterus / metabolism

Substances

  • Nifedipine