title: Windows of therapeutic opportunity on fetal growth retardation induced by transient intrauterine ischemia in rats.
abstract: OBJECTIVE
  To assess the windows of therapeutic opportunity for drugs with various chemical actions on fetal growth retardation induced by transient intrauterine ischemia in rats.
  
  
  METHODS
  At 17 days of gestation, ischemia was induced by 30 min of right uterine artery occlusion. The administration of either alpha-phenyl-N-tert-butyl-nitrone (PBN), FK 506, nifedipine, or MK-801 to pregnant rats was randomly started before occlusion, 1 hour, 3 hours, or 24 hours after recirculation. All of the pups were delivered by cesarean section at 21 days of gestation and were weighed to determine the degree of fetal growth retardation.
  
  
  RESULTS
  The vehicle-treated animals exposed to ischemia showed a significant decrease in fetal body weight compared with the normoxic control animals. The growth disturbances were prevented by nifedipine and MK-801 only when given just prior to ischemia. In contrast, PBN and FK 506 had a protective effect even when given 1 hour and 3 hours after the start of recirculation, respectively.
  
  
  CONCLUSIONS
  The present results indicate that treatment with PBN and FK 506 gives relatively wide windows of therapeutic opportunity in fetal growth retardation induced by transient intrauterine ischemia in rats and suggest the possibility of therapeutic intervention after the start of recirculation.
authors.affiliation: Department of Obstetrics and Gynecology, Tama Nagayama Hospital, Nippon Medical School, Tama-shi, Tokyo, Japan. nakai-3@nms.ac.jp
authors.forename: Akihito
authors.initials: A
authors.lastname: Nakai
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Taniuchi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Oya
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Asakura
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Koshino
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Araki
mesh_terms: D000818:Animals; D003497:Cyclic N-Oxides; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D005260:Female; D005317:Fetal Growth Retardation / Q000188:drug therapy* / Q000209:etiology; D005311:Fetal Hypoxia / Q000150:complications; D007511:Ischemia / Q000150:complications; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009543:Nifedipine / Q000627:therapeutic use; D009589:Nitrogen Oxides / Q000627:therapeutic use*; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D003497:Cyclic N-Oxides; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; D016291:Dizocilpine Maleate; D009543:Nifedipine; D016559:Tacrolimus