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 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.