Journal of Nippon Medical School: Vol.69 No.6 page.534

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ArticleTitle Windows of Therapeutic Opportunity on Fetal Growth Retardation Induced by Transient Intrauterine Ischemia in Rats

AuthorList Akihito Nakai, Yoshinari Taniuchi, Atsuko Oya, Hirobumi Asakura, Tatsuo Koshino and Tsutomu Araki

Affiliation Department of Obstetrics and Gynecology, Nippon Medical School

Language EN

Volume 69

Issue 6

Year 2002

Page 534-541

Received April 23, 2002

Accepted May 27, 2002

Keywords fetal growth retardation, intrauterine ischemia, BPN, FK 506, nifedipine, MK-801

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 α-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.

Correspondence to Akihito Nakai, MD, Department of Obstetrics and Gynecology, Tama Nagayama Hospital, Nippon Medical School, 1-7-1 Nagayama, Tama-shi, Tokyo 206-8512, Japan
nakai-3@nms.ac.jp

ArticleTitle	Windows of Therapeutic Opportunity on Fetal Growth Retardation Induced by Transient Intrauterine Ischemia in Rats
AuthorList	Akihito Nakai, Yoshinari Taniuchi, Atsuko Oya, Hirobumi Asakura, Tatsuo Koshino and Tsutomu Araki
Affiliation	Department of Obstetrics and Gynecology, Nippon Medical School
Language	EN
Volume	69
Issue	6
Year	2002
Page	534-541
Received	April 23, 2002
Accepted	May 27, 2002
Keywords	fetal growth retardation, intrauterine ischemia, BPN, FK 506, nifedipine, MK-801
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 α-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.
Correspondence to	Akihito Nakai, MD, Department of Obstetrics and Gynecology, Tama Nagayama Hospital, Nippon Medical School, 1-7-1 Nagayama, Tama-shi, Tokyo 206-8512, Japan nakai-3@nms.ac.jp