EFFECT OF INHIBITION OF PROSTAGLANDIN SYNTHESIS ON BREATHING MOVEMENTS AND PULMONARY BLOOD-FLOW IN FETAL SHEEP

During transition from fetal to extrauterine life, respiration increas es in incidence and magnitude as pulmonary blood flow dramatically inc reases. To determine whether alterations in pulmonary blood flow in ut ero are directly related to alterations in fetal breathing movements ( FBM), we studied six chronically instrumented fetal sheep late in gest ation to assess the effects of continuous FBM caused by a 4-h infusion of meclofenamate, a prostaglandin synthase inhibitor, on mean pulmona ry blood flow to the fetus. We found a striking increase in FBM from 4 6 +/- 15% (SD) of the time during control to >85% of the time by 1 h ( P < 0.001), with the fetuses exhibiting continuous FBM by the last 1 h of infusion. The mean pulmonary blood flow also increased significant ly during the first 90 min of the infusion as the incidences of FBM we re increasing (26 +/- 14 and 56 +/- 23 ml.min(-1).kg(-1) for control a nd infusion, respectively; P < 0.01). Despite the simultaneous initial increase in FBM and mean pulmonary blood flow, the increase in left p ulmonary artery blood flow was not sustained and decreased back to bas eline by 2 h, even though the incidence of FBM continued to increase a t this time. During the infusion, the mean pulmonary blood flow was no t different between the presence or absence of FBM. There were no chan ges in fetal heart rate or pulmonary or systemic blood pressures durin g the infusion nor in arterial pH or blood gas tensions. We conclude t hat this increase in mean pulmonary blood flow in utero was not solely related to the increase in breathing movements.