Effects of meclofenamate on breathing movements in fetal sheep before delivery

There is evidence that prostaglandins (PG), specifically PGE2, participate in the regulation of fetal breathing movements (FBM). During late gestation, when FBM occur intermittently and primarily during low-voltage electrocortical activity, the concentration of PGE2 in fetal plasma ([PGE2]) is high. During the days before delivery [PGE2] increases and FBM decrease. To determine whether the increase in [PGE2] is responsible for the concurrent decrease in FBM, we infused the prostaglandin synthase inhibitor, meclofenamate (0.7 mg.kg-1.h-1), into eight fetal sheep continuously for 5-13 days before delivery; five control fetuses received a continuous infusion of the solvent for 5-11 days before delivery. Compared with control infusion, meclofenamate caused a significant decrease in [PGE 2] until the day of delivery and a significant increase in FBM [overall and during high-voltage electrocortical activity (HVA)] until 2 days before delivery. Although there were significant correlations between [PGE2] and FBM (overall and during HVA), both groups showed similar decreases in FBM during the 2 days before delivery. We conclude that the decrease in FBM before delivery is not dependent on the concurrent increase in [PGE2].